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Importance: Previous studies investigated atherosclerotic changes induced by lipid-lowering therapy in extensive coronary segments irrespective of baseline disease burden (a vessel-level approach)., Objective: To investigate the effects of lipid-lowering therapy on coronary lesions with advanced atherosclerotic plaque features and presumably higher risk for future events., Design, Setting, and Participants: The PACMAN-AMI randomized clinical trial (enrollment: May 2017 to October 2020; final follow-up: October 2021) randomized patients with acute myocardial infarction to receive alirocumab or placebo in addition to high-intensity statin therapy. In this post hoc lesion-level analysis, nonculprit lesions were identified as segments with plaque burden 40% or greater defined by intravascular ultrasound (IVUS). IVUS, near-infrared spectroscopy, and optical coherence tomography images at baseline and the 52-week follow-up were manually matched by readers blinded to treatment allocation. Data for this study were analyzed from October 2022 to November 2023., Interventions: Alirocumab or placebo in addition to high-intensity statin therapy., Main Outcomes and Measures: Lesion-level imaging outcome measures, including high-risk plaque characteristics and phenotypes., Results: Of the 245 patients in whom lesions were found, 118 were in the alirocumab group (mean [SD] age, 58.2 [10.0] years; 101 [85.6%] male and 17 [14.4%] female) and 127 in the placebo group (mean [SD] age, 57.7 [8.8] years; 104 [81.9%] male and 23 [18.1%] female). Overall, 591 lesions were included: 287 lesions (118 patients, 214 vessels) in the alirocumab group and 304 lesions (127 patients, 239 vessels) in the placebo group. Lesion-level mean change in percent atheroma volume (PAV) was -4.86% with alirocumab vs -2.78% with placebo (difference, -2.02; 95% CI, -3.00 to -1.05; P < .001). At the minimum lumen area (MLA) site, mean change in PAV was -10.14% with alirocumab vs -6.70% with placebo (difference, -3.36; 95% CI, -4.98 to -1.75; P < .001). MLA increased by 0.15 mm2 with alirocumab and decreased by 0.07 mm2 with placebo (difference, 0.21; 95% CI, 0.01 to 0.41; P = .04). Among 122 lipid-rich lesions, 34 of 55 (61.8%) in the alirocumab arm and 27 of 67 (41.8%) in the placebo arm showed a less lipid-rich plaque phenotype at follow-up (P = .03). Among 63 lesions with thin-cap fibroatheroma at baseline, 8 of 26 (30.8%) in the alirocumab arm and 3 of 37 (8.1%) in the placebo arm showed a fibrous/fibrocalcific plaque phenotype at follow-up (P = .02)., Conclusions and Relevance: At the lesion level, very intensive lipid-lowering therapy induced substantially greater PAV regression than described in previous vessel-level analyses. Compared with statin therapy alone, alirocumab treatment was associated with greater enlargement of the lesion MLA and more frequent transition of presumably high-risk plaque phenotypes into more stable, less lipid-rich plaque phenotypes., Trial Registration: ClinicalTrials.gov Identifier: NCT03067844.

Objective:  The effect of the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor alirocumab on platelet aggregation among patients with acute myocardial infarction (AMI) remains unknown. We aimed to explore the effect of alirocumab added to high-intensity statin therapy on P2Y12 reaction unit (PRU) among AMI patients receiving dual antiplatelet therapy (DAPT) with a potent P2Y12 inhibitor (ticagrelor or prasugrel). In addition, we assessed circulating platelet-derived noncoding RNAs (microRNAs and YRNAs)., Methods:  This was a prespecified, powered, pharmacodynamic substudy of the PACMAN trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) versus placebo in AMI patients undergoing percutaneous coronary intervention. Patients recruited at Bern University Hospital, receiving DAPT with a potent P2Y12 inhibitor, and adherent to the study drug (alirocumab or placebo) were analyzed for the current study. The primary endpoint was PRU at 4 weeks after study drug initiation as assessed by VerifyNow P2Y12 point-of-care assays., Results:  Among 139 randomized patients, the majority of patients received ticagrelor DAPT at 4 weeks (57 [86.4%] in the alirocumab group vs. 69 [94.5%] in the placebo group, p  = 0.14). There were no significant differences in the primary endpoint PRU at 4 weeks between groups (12.5 [interquartile range, IQR: 27.0] vs. 19.0 [IQR: 30.0], p  = 0.26). Consistent results were observed in 126 patients treated with ticagrelor (13.0 [IQR: 20.0] vs. 18.0 [IQR: 27.0], p  = 0.28). Similarly, platelet-derived noncoding RNAs did not significantly differ between groups., Conclusion:  Among AMI patients receiving DAPT with a potent P2Y12 inhibitor, alirocumab had no significant effect on platelet reactivity as assessed by PRU and platelet-derived noncoding RNAs., Competing Interests: Y.U. reports personal fees from Infraredx outside the submitted work. S.L. is employed by CTU Bern, University of Bern, which has a staff policy of not accepting honoraria or consultancy fees. However, CTU Bern is involved in design, conduct, or analysis of clinical studies funded by not-for-profit and for-profit organizations. In particular, pharmaceutical and medical device companies provide direct funding to some of these studies. D.S. reports receiving personal fees from Sanofi-Aventis (Suisse) outside the submitted work. S.S. reports research grants to the institution from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott, and personal fees from Boston Scientific, Teleflex, and BTG. M.V. reports research grants to the institution from Terumo and Concept Medical and consulting fees from AstraZeneca, Terumo, Alvimedica/CID, Abiomed, Amgen, Abbott Vascular, Daiichi Sankyo, Bayer, CoreFLOW, DORSIA PHARMACEUTICALS LTD, Universität Basel Dept. Klinische Forschung, Vifor, Bristol Myers Squib SA, Biotronik, Boston Scientific, Medtronic, Vesalio, Novartis, Chiesi, PhaseBio, and ECRI, outside the submitted work. S.W. reports research and educational grants to the institution from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Corflow Therapeutics, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medicure, Medtronic, Merck Sharp & Dohm, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi-Aventis, Servier, Sinomed, Terumo, Vifor, and V-Wave. S.W. serves as unpaid advisory board member and/or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave, and Xeltis, but has not received personal payments by pharmaceutical companies or device manufacturers. He is also member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. M.M. is a British Heart Foundation (BHF) Chair Holder (CH/16/3/32406) with BHF program grant support (RG/F/21/110053). He is also supported by the Leducq Foundation (18CVD02) and VASCage-C (Research Centre on Vascular Aging and Stroke), an R&D K-Centre of the Austrian Research Promotion Agency (COMET program—Competence Centres for Excellent Technologies) funded by the Austrian Ministry for Transport, Innovation and Technology, the Austrian Ministry for Digital and Economic Affairs, and the federal states Tyrol, Salzburg, and Vienna with the grant number FSG 868624. He has filed and licensed patents on microRNAs as biomarkers. L.R. received a grant to the institution for the conduction of the PACMAN AMI study by Sanofi, Regeneron, and Infraredx. L.R. received research grants to the institution by Abbott, Boston Scientific, Biotronik, and Heartflow, and speaker or consultation fees by Abbott, Amgen, AstraZeneca, Canon, Novo Nordisk, Medtronic, Occlutech, and Sanofi., (Thieme. All rights reserved.)

Background : We aimed to study the long-term safety and efficacy of oblique venous stents for post-thrombotic syndrome (PTS) with iliac vein compression. Patients and methods : In the multinational, prospective, single-arm TOPOS study, PTS patients scheduled for endovascular therapy with the sinus-Obliquus ® stent and optional distal extension with the sinus-Venous ® or sinus-XL Flex ® stent were enrolled at eight European vascular centres between October 2016 and December 2020. The primary outcome was primary stent patency at 24 months, and secondary outcomes included the clinical course of PTS (Villalta score, revised Venous Clinical Severity Score [rVCSS], Visual Analog Scale [VAS] of pain), quality of life changes (Chronic Venous Insufficiency Quality of Life Questionnaire, CIVIQ-20), and device-related complications. Results : We enrolled 60 patients (mean age 46±15 years, 68% women, 13% active ulcers): 80% required stent extension (70% below the inguinal ligament). The primary patency rate at 24 months was 80.7% (95%CI 68.1-90.0%); it was higher in patients without vs. those with stent extension (90.9% vs. 78.3%, p=.01). Compared to baseline, the Villalta, rVCSS, pain VAS, and CIVIQ-20 decreased by a median of 8 (interquartile range (IQR): 4-11), 5 (IQR: 3-7), 3 (IQR: 2-5), and 17 (IQR: 6-22) points, respectively; p<.001 for all parameters. Overall, 9 events of acute stent occlusion, 4 symptomatic stent stenosis, and 1 pulmonary embolism occurred. We did not observe major bleeding events or contralateral thrombosis. Conclusions : Endovascular treatment with the oblique stent and optional stent extension was safe and resulted in high patency rates at 24 months. The reduction in PTS severity was substantial and persisted over 2-year follow-up.

Background: Pharmaco-mechanical thrombectomy (PMT) and catheter-directed thrombolysis (CDT) are therapeutic options for selected patients with acute deep vein thrombosis (DVT) to prevent post-thrombotic syndrome (PTS). Patients and methods: We aimed to describe the clinical characteristics and outcomes of 159 patients with symptomatic iliofemoral DVT undergoing PMT alone, CDT alone, or CDT followed by PMT (bail-out) in the Swiss Venous Stent Registry. The primary outcome was the incidence of peri-interventional major and minor bleeding complications (ISTH criteria). Secondary outcomes included the incidence of PTS and stent patency after 3 years. Results: Mean age was 49±20 years and 58% were women. DVT involved the iliac veins in 99% of patients, whereas 53% had an underlying iliac vein compression. PMT alone was used in 40 patients, CDT alone in 77, and 42 received initial CDT followed by bail-out PMT due to insufficient thrombus clearance. Single-session PMT was the preferred approach in patients with iliac vein compression, patent popliteal vein, and absence of IVC thrombus. Patients treated with PMT alone received a lower r-tPA dose (median 10 mg, IQR 10-10) vs. those treated with CDT (20 mg, IQR 10-30). The rate of peri-interventional major bleeding was 0%, 1%, and 2%, whereas that of minor bleeding was 0%, 1%, and 12%, respectively, all occurring during CDT. After 3 years, PTS occurred in 6%, 9%, and 7% of patients, respectively. The primary stent patency rate was 95%, 88%, and 83%, respectively. Conclusions: The use of PMT and CDT for iliofemoral DVT was overall safe and resulted in high long-term patency and treatment success. Given the less severe presentation of DVT, single-session PMT appeared to be characterized by numerically better primary patency and lower perioperative bleeding event rates than CDT.

Background: The frequency, characteristics, and outcomes of patients treated with high-intensity lipid-lowering therapy and showing concomitant atheroma volume reduction, lipid content reduction, and increase in fibrous cap thickness (ie, triple regression) are unknown., Objectives: This study was designed to investigate rates, determinants, and prognostic implications of triple regression in patients presenting with acute myocardial infarction and treated with high-intensity lipid-lowering therapy., Methods: The PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients with Acute Myocardial Infarction) trial used serial intravascular ultrasound, near-infrared spectroscopy, and optical coherence tomography to compare the effects of alirocumab vs placebo in patients receiving high-intensity statin therapy. Triple regression was defined by the combined presence of percentage of atheroma volume reduction, maximum lipid core burden index within 4 mm reduction, and minimal fibrous cap thickness increase. Clinical outcomes at 1-year follow-up were assessed., Results: Overall, 84 patients (31.7%) showed triple regression (40.8% in the alirocumab group vs 23.0% in the placebo group; P = 0.002). On-treatment low-density lipoprotein cholesterol levels were lower in patients with vs without triple regression (between-group difference: -27.1 mg/dL; 95% CI: -37.7 to -16.6 mg/dL; P < 0.001). Triple regression was independently predicted by alirocumab treatment (OR: 2.83; 95% CI: 1.57-5.16; P = 0.001) and a higher baseline maximum lipid core burden index within 4 mm (OR: 1.03; 95% CI: 1.01-1.06; P = 0.013). The composite clinical endpoint of death, myocardial infarction, and ischemia-driven revascularization occurred less frequently in patients with vs without triple regression (8.3% vs 18.2%; P = 0.04)., Conclusions: Triple regression occurred in one-third of patients with acute myocardial infarction who were receiving high-intensity lipid-lowering therapy and was associated with alirocumab treatment, higher baseline lipid content, and reduced cardiovascular events. (Vascular Effects of Alirocumab in Acute MI-Patients [PACMAN-AMI]; NCT03067844)., Competing Interests: Funding Support and Author Disclosures This study was conducted in an independent academic setting and funded by Bern University Hospital. Dr Ueki has received personal fees and nonfinancial support from NIPRO; and has received personal fees from Amgen, Daiichi-Sankyo, Abbott Vascular, Kowa, and Novartis, outside the submitted work. Dr Kakizaki has received speaker fees from Abbott Medical Japan, Philips Japan, Mochida Pharmaceutical Japan, Novartis Japan, Kowa Japan, Takeda Pharmaceuticals Japan, Ono Pharmaceutical Japan, Boehringer Ingelheim Japan, Daiichi-Sankyo Japan, Mitsubishi Tanabe Pharma Japan, and Eli Lilly Japan, outside the submitted work. Dr Hofbauer has received speaker fees from Sanofi. Dr Stortecky has received research grants paid to the institution from Edwards Lifesciences, Medtronic, Abbott Vascular, and Boston Scientific; and has received speaker fees from Boston Scientific. Dr Bär has received research grants paid to the institution from Medis Medical Imaging, Abbott, and Bangerter-Rhyner Stiftung, outside the submitted work; and has received a personal research grant from the Swiss National Science Foundation, outside the submitted work. Dr Spirk has received personal fees from Sanofi (Suisse), outside the submitted work. Dr Räber has received grants from Sanofi, Regeneron, and Infraredx paid to Inselspital; has received speaker fees from Sanofi during the conduct of the study; has received grants from Abbott, Heartflow, Boston Scientific, and Biotronik paid to Inselspital; and has received grants from Abbott, Amgen, AstraZeneca, Occlutech, Sanofi, Canon, and Medtronic for speaker and consultation fees outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Antithrombotic treatment may improve the disease course in non-critically ill, symptomatic COVID-19 outpatients., Methods: We performed an individual patient-level analysis of the OVID and ETHIC randomized controlled trials, which compared enoxaparin thromboprophylaxis for either 14 (OVID) or 21 days (ETHIC) vs. no thromboprophylaxis for outpatients with symptomatic COVID-19 and at least one additional risk factor. The primary efficacy outcome included all-cause hospitalization and all-cause death within 30 days from randomization. Both studies were prematurely stopped for futility. Secondary efficacy outcomes were major symptomatic venous thromboembolic events, arterial cardiovascular events, or their composite occurring within 30 days from randomization. The same outcomes were assessed over a 90-day follow-up. The primary safety outcome was major bleeding (ISTH criteria)., Results: A total of 691 patients were randomized: 339 to receive enoxaparin and 352 to the control group. Over 30-day follow-up, the primary efficacy outcome occurred in 6.0 % of patients in the enoxaparin group vs. 5.8 % of controls for a risk ratio (RR) of 1.05 (95%CI 0.57-1.92). The incidence of major symptomatic venous thromboembolic events and arterial cardiovascular events was 0.9 % vs. 1.8 %, respectively (RR 0.52; 95%CI 0.13-2.06). Most cardiovascular thromboembolic events were represented by symptomatic venous thromboembolic events, occurring in 0.6 % vs. 1.5 % of patients, respectively. A similar distribution of outcomes between the treatment groups was observed over 90 days. No major bleeding occurred in the enoxaparin group vs. one (0.3 %) in the control group., Conclusions: We found no evidence for the clinical benefit of early administration of enoxaparin thromboprophylaxis in outpatients with symptomatic COVID-19. These results should be interpreted taking into consideration the relatively low occurrence of events., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Stefano Barco reports grants or contracts from Bayer, INARI, Boston Scientific, Medtronic, Bard, Sanofi, and Concept Medical; consulting fees from INARI; payment or honoraria from INARI, Boston Scientific, Penumbra and Concept Medical; and support for attending meetings and/or travel from Bayer and Sanofi. Roland Bingisser reports no conflicts of interest. Stefan Stortecky has received research grants to the institution from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific and Guerbet AG and speaker fees from Boston Scientific. Giuseppe Colucci reports no conflicts of interest. Bernhard Gerber reports non-financial support and funding for an accredited continuing medical education programme from Axonlab, and Thermo Fisher Scientific; personal fees and funding for an accredited continuing medical education programme from Alnylam, Pfizer, and Sanofi; funding for an accredited continuing medical education programme from Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Takeda, Octapharma, SOBI, Janssen, Novo Nordisk, Mitsubishi Pfizer, Tanabe Pharma, outside the submitted work. Jelle C L Himmelreich reports no conflicts of interest. DS reports employment by Sanofi-Aventis Switzerland. Thomas Rosemann reports no conflicts of interest. Walter Ageno reports research grants from Bayer; advisory boards for Bayer, Leo Pharma, Norgine, Sanofi, Techdow, Viatris. Juan Ignacio Arcelus declares speaker fees from Sanofi and Rovi. H.G reports personal fees from Pfizer, Bayer, Boehringer Ingelheim. Peter MacCallum reports no conflicts of interest. Daniel Duerschmied has received consulting fees from Boston Scientific and speakers' honoraria from Bayer, Daiichi Sankyo, Boston Scientific, Boehringer Ingelheim, and BMS/Pfizer. Tim Sebastian reports no conflicts of interest. Sylvia Haas reports honoraria from Bayer, BMS, Daiichi-Sankyo, Pfizer and Sanofi. Lukas Hobohm received lecture/consultant fees from Johnson&Johnson, INARI, MSD and Boston Scientific; outside the submitted work. The other authors report no conflicts of interest. Renato D Lopes reports research grants or contracts from Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, Sanofi-Aventis; funding for educational activities or lectures from Pfizer, Bristol-Myers Squibb, Novo Nordisk, AstraZeneca, and unding for consulting from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Novo Nordisk, AstraZeneca., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on top of statins leads to plaque regression and stabilisation. The effects of PCSK9 inhibitors on coronary physiology and angiographic diameter stenosis (DS%) are unknown., Aims: This study aimed to investigate the effects of the PCSK9 inhibitor alirocumab on coronary haemodynamics as assessed by quantitative flow ratio (QFR) and DS% by three-dimensional quantitative coronary angiography (3D-QCA) in non-infarct-related arteries (non-IRA) among acute myocardial infarction (AMI) patients., Methods: This was a prespecified substudy of the randomised controlled PACMAN-AMI trial, comparing alirocumab versus placebo on top of rosuvastatin. QFR and 3D-QCA were assessed at baseline and 1 year in any non-IRA ≥2.0 mm and 3D-QCA DS% >25%. The prespecified primary endpoint was the number of patients with a mean QFR increase at 1 year, and the secondary endpoint was the change in 3D-QCA DS%., Results: Of 300 enrolled patients, 265 had serial follow-up, of which 193 underwent serial QFR/3D-QCA analysis in 282 non-IRA. At 1 year, QFR increased in 50/94 (53.2%) patients with alirocumab versus 40/99 (40.4%) with placebo (Δ12.8%; odds ratio 1.7, 95% confidence interval [CI]: 0.9 to 3.0; p=0.076). DS% decreased by 1.03±7.28% with alirocumab and increased by 1.70±8.27% with placebo (Δ-2.50%, 95% CI: -4.43 to -0.57; p=0.011)., Conclusions: Treatment of AMI patients with alirocumab versus placebo for 1 year resulted in a significant regression in angiographic DS%, whereas no overall improvement of coronary haemodynamics was observed., Clinicaltrials: gov: NCT03067844.

Background and Aims: Peripheral arterial disease (PAD) is one of the most prevalent cardiovascular diseases with more than 230 million people being affected worldwide. As highlighted by the recent European Society of Cardiology guidelines, data on the epidemiology of PAD is urgently needed., Methods and Results: We accessed the vital registration data of the Veneto region (Northern Italy, approximately five millions inhabitants) covering the period 2008-2019. We computed annual age-standardized rates for PAD reported as the underlying cause of death (UCOD) or as one of multiple causes of death (MCOD). Age-adjusted odds ratios (OR) served to study the association between PAD and cardiovascular comorbidities. The age-standardized mortality rate for PAD as MCOD slightly declined from 19.6 to 17.8 in men and from 10.8 to 9.1 deaths per 100,000 population-years in women. The age-standardized PAD-specific mortality rate (UCOD) remained stable: 3.1 to 3.7 per 100,000 person-years in women (Average Annual Percent Change 1.3, 95% CI -0.8; 3.4%) and 4.4 to 4.3 per 100,000 person-years (Average Annual Percent Change -0.2, 95% CI -3.6; 3.4%) in men. PAD contributed to 1.6% of all deaths recorded in the region. Ischemic heart disease, diabetes mellitus and neoplasms were the most prevalent UCOD among PAD patients. PAD was associated with diabetes mellitus (OR 3.79, 95%CI 3.55-4.06) and chronic kidney diseases (OR 2.73, 95%CI 2.51-2.97) in men, and with atrial fibrillation (OR 2.26, 95%CI 2.10-2.44) in women., Conclusion: PAD remains a substantial cause of death in the general population of this high-income region of Western Europe with marked sex-specific differences., Competing Interests: Declaration of competing interest Stefano Barco has received congress and travel payments from Daiichi-Sankyo, Boston Scientific, and Bayer HealthCare; institutional grants from Sanofi, Boston Scientific, Bard, and Bayer HealthCare; and personal fees and honoraria from Bayer HealthCare, LeoPharma, Boston Scientific, and Daiichi-Sankyo, outside the present work. David Spirk reports employment by Sanofi-Aventis. Nils Kucher reports grants from Concept Medical, Bard, and Bayer; and personal fees from Bayer, Bard, Medtronic, Boston Scientific, BTG, and Pfizer, outside the submitted work. Marc Righini has received speaker's honoraria from Bayer, Daïchi Sankyo, Pfizer/BMS, and Biomérieux. The other authors have nothing to disclose., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: The benefits of early thromboprophylaxis in symptomatic COVID-19 outpatients remain unclear. We present the 90-day results from the randomised, open-label, parallel-group, investigator-initiated, multinational OVID phase III trial., Methods: Outpatients aged 50 years or older with acute symptomatic COVID-19 were randomised to receive enoxaparin 40 mg for 14 days once daily vs. standard of care (no thromboprophylaxis). The primary outcome was the composite of untoward hospitalisation and all-cause death within 30 days from randomisation. Secondary outcomes included arterial and venous major cardiovascular events, as well as the primary outcome within 90 days from randomisation. The study was prematurely terminated based on statistical criteria after the predefined interim analysis of 30-day data, which has been previously published. In the present analysis, we present the final, 90-day data from OVID and we additionally investigate the impact of thromboprophylaxis on the resolution of symptoms., Results: Of the 472 patients included in the intention-to-treat population, 234 were randomised to receive enoxaparin and 238 no thromboprophylaxis. The median age was 57 (Q1-Q3: 53-62) years and 217 (46 %) were women. The 90-day primary outcome occurred in 11 (4.7 %) patients of the enoxaparin arm and in 11 (4.6 %) controls (adjusted relative risk 1.00; 95 % CI: 0.44-2.25): 3 events per group occurred after day 30. The 90-day incidence of cardiovascular events was 0.9 % in the enoxaparin arm vs. 1.7 % in controls (relative risk 0.51; 95 % CI: 0.09-2.75). Individual symptoms improved progressively within 90 days with no difference between groups. At 90 days, 42 (17.9 %) patients in the enoxaparin arm and 40 (16.8 %) controls had persistent respiratory symptoms., Conclusions: In adult community patients with COVID-19, early thromboprophylaxis with enoxaparin did not improve the course of COVID-19 neither in terms of hospitalisation and death nor considering COVID-19-related symptoms., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bernhard Gerber reports non-financial support and funding for an accredited continuing medical education programme from Axonlab, and Thermo Fisher Scientific; personal fees and funding for an accredited continuing medical education programme from Alnylam, Pfizer, and Sanofi; funding for an accredited continuing medical education programme from Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Takeda, Octapharma, SOBI, Janssen, Novo Nordisk, Mitsubishi Pfizer, Tanabe Pharma, outside the submitted work. Stavros V. Konstantinides reports grants or contracts from Bayer AG; consulting fees from Bayer, Daiichi Sankyo, and Boston Scientific; and payment or honoraria from Bayer, INARI Medical, MSD, Pfizer, and Bristol-Myers Squibb. Stefan Stortecky reports research grants from Edwards Lifesciences to the institution, research grants from Medtronic to the institution, research grants from Boston Scientific to the institution, research grants from Abbott to the institution, personal fees from Boston Scientific, from Teleflex, from BTG –Boston Scientific outside the submitted work. Helia Robert-Ebadi reports speaker honoraria from Daichi-Sankyo, and Bayer. David Spirk reports employment by Sanofi-Aventis Switzerland. Daniel Duerschmied reports research support from German Research Foundation, CytoSorbents, Haemonetic; consulting and speaker's fees from Bayer Healthcare, Daiichi Sankyo, LEO Pharma, AstraZeneca, Boston Scientific, and BMS–Pfizer. Nils Kucher reports institutional research grants from Concept Medical, Bard, Bentley, Boston Scientific, INARI, Sanofi, and Bayer; and personal fees from Concept Medical, Bayer, Boston Scientific, and INARI. Stefano Barco reports institutional research grants from Concept Medical, Bard, Bentley, Boston Scientific, INARI, Sanofi, and Bayer; and personal fees from Concept Medical, Bayer, Boston Scientific, and INARI. All other authors do not report any conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Although the two manifestations of venous thromboembolism (VTE), deep vein thrombosis (DVT) and pulmonary embolism (PE), vary considerably, the consensus guidelines recommend similar algorithms for therapeutic anticoagulation in both conditions. Real-world data assessing contemporary management strategies in PE and DVT alone may help tailoring future recommendations towards more individualized patient care., Methods: In the present analysis, we compared demographics, comorbidities, treatment patterns, and clinical outcomes of PE versus DVT only among 2062 consecutive patients with confirmed VTE enrolled by 11 acute care hospitals between November 2012 and February 2015 in the SWIss Venous ThromboEmbolism Registry (SWIVTER)., Results: Overall, 1246 (60 %) patients were diagnosed with PE. In comparison to DVT alone, PE patients were older (66 vs. 59 years; p < 0.001), more frequently had acute and chronic comorbidities, less frequently had prior VTE and hormone replacement, and were less often pregnant. VTE was considered similarly often provoked in patients with PE and DVT alone (33.8 % vs. 33.5 %; p = 0.88). Anticoagulation for an indefinite duration was more often prescribed to patients with PE than those with DVT alone (45.7 vs. 19.6 %; p < 0.001), and PE diagnosis was the strongest independent predictor of indefinite anticoagulation (OR 3.21; 95 % CI 2.55-4.06; p < 0.001). Diagnosis of PE was associated with both increased risk of 90-day mortality (HR 2.31, 95 % CI 1.44-3.71; p = 0.001) and major bleeding (HR 3.88, 95 % CI 1.63-9.22; p = 0.002)., Conclusions: Our analysis affirms differences in demographics, risk factors, and clinical outcomes of PE versus DVT alone. In routine clinical practice, duration of anticoagulation is being managed differently between the two manifestations of VTE, in contrast to recommendations of the current consensus guidelines., Competing Interests: Conflict of interest JHB reports grants from the Swiss National Science Foundation and the Swiss Heart Foundation, grants, and personal fees from Boehringer Ingelheim, Pfizer, Bayer, and Daiichi-Sankyo, outside the submitted work. RPE reports personal fees from Bayer, Daiichi-Sankyo and Sanofi-Aventis, outside the submitted work. WK reports personal fees and non-financial support from Bayer, Pfizer, Shire/Takeda, Roche, Daiichi-Sankyo, and Novo Nordisk, outside the submitted work. NK reports personal fees from Bayer, Boston Scientific, Optimed, Bard, and BTG, outside the submitted work. SB reports personal fees from BTG Pharmaceuticals and Leo Pharma, personal fees and non-financial support from Bayer HealthCare, and non-financial support from Daiichi-Sankyo, outside the submitted work. DS is an employee of Sanofi-Aventis (Suisse) SA, Vernier, Switzerland., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Statin intolerance (SI) is often documented in patients’ charts but rarely confirmed by objective methods. Objective: We aimed to identify the rate of true SI in a large population with peripheral artery disease (PAD) as well as the subsequent use of such drugs and the impact on cardiovascular outcomes. Methods: Patients with PAD and reported SI were retrospectively classified in those with “probable/possible” (pp) and “unlikely” (u) SI, after the application of the “Statin Myalgia Clinical Index Score” (SAMS-CI). Both groups were compared after 62 months (date of observation period?). Results: Among the 4,505 included patients, 139 (3%) had been reported as having SI. Of those, 33 (24%) had ppSI, and 106 (76%) had uSI. During the observation period, statin use decreased in patients with both ppSI (from 97% to 21%; p < 0.0001) and uSI (from 87% to 53%; p < 0.0001). At the end of the observation period, patients with ppSI more often received PCSK9 inhibitors (55% vs. 7%; p < 0.0001), had a stronger decrease in LDL-C from baseline to follow-up (1.82 ± 1.69 mmol/L vs. 0.85 ± 1.41 mmol/L; p < 0.01), and a lower rate of mortality (3% vs. 21%; p = 0.04) than those with uSI. Conclusions: SI is low in PAD patients (3.1%), with only one quarter fulfilling the criteria of ppSI. The overdiagnosis of SI is related to an underuse of statins and an increased mortality in a short time period.

Background: The global burden of peripheral arterial disease (PAD) is substantial. Reducing the major modifiable risk factors for noncommunicable disease, including dyslipidaemia, represents a public health priority. Aim is to evaluate the prevalent adequate use of lipid-lowering therapy (LLT) and low-density lipoprotein cholesterol (LDL-C) attainment among patients with PAD of the lower extremities undergoing percutaneous transluminal angioplasty. Patients and methods: We screened PAD patients treated at the University Hospital Zurich (January 2012-December 2018). We excluded patients <18 years, without classifiable severity of PAD, or with missing LDL-C or medication data. In this cross-sectional study, we studied the prevalent LLT use and LDL-C values in target according to the most recent European guidelines. Available clinical data included demographic information, lipid profile, type and dose of LLT, characteristics of the artery obstruction and angioplasty. Results: A total of 2,148 angioplasties were performed in 956 patients: 614 (64%) were men; the mean age was 70.6 (SD 11.4) years. A total of 608 (64%) had a non-critical PAD (Fontaine stage I-IIb), whereas the remaining had a critical limb ischemia or a diabetic foot syndrome. Their median LDL-C value was 2.00 (Q1-Q3: 1.50-2.60) mmol/L. In accordance to the 2016 and 2019 European Society of Cardiology guidelines, the LDL-C target of 1.8 and 1.4 mmol/L was not reached in 63% (n=599) and in 79% (n=760) of patients, respectively. Only 41% (n=390) of patients were on high-intensity statin therapy. Conclusions: The attainment of LDL-C targets, as recommended by current European guidelines, and the use of high-intensity LLT were unsatisfactory in the majority of PAD patients.

Background: The direct factor Xa inhibitor rivaroxaban is approved for the treatment of venous thromboembolism (VTE), based on the results of large phase III trials., Objectives: To confirm rivaroxaban's effectiveness and safety in routine clinical care of patients with VTE., Methods: Data were obtained from prospective, noninterventional registries: the FIRST registry (United Kingdom), DRESDEN NOAC registry (Germany), and SWIVTER (Switzerland). Baseline characteristics of these registries and effectiveness and safety outcome rates for the FIRST and DRESDEN NOAC registries were compared., Results: A total of 1841 rivaroxaban-treated patients with acute VTE (57.9% male, 76.6% deep vein thrombosis [DVT]; 23.4% pulmonary embolism ± DVT; median age, 61 years) were included: 1217 from the FIRST registry, 418 from the DRESDEN NOAC registry, and 206 from SWIVTER. Median time between VTE diagnosis and initiation of rivaroxaban was 1.4 ± 1.81 days (25th-75th percentile 1-1; range, 0-15 days). On-treatment outcome rates for the FIRST and DRESDEN NOAC registries were 0.74 per 100 patient-years (95% confidence interval [CI], 0.35-1.54) versus 0.96 per 100 patient-years (95% CI, 0.46-2.01) for VTE recurrence; 1.16 per 100 patient years (95% CI, 0.64-2.09) versus 2.51 per 100 patient-years (95% CI, 1.58-3.98) for ISTH major bleeding and 1.69 per 100 patient-years (95% CI, 1.21-2.35) versus 1.73 per 100 patient-years (95% CI, 1.27-2.36) for all-cause mortality (intention-to-treat analysis), respectively., Conclusion: Overall treatment outcomes were consistent with the results of the phase III rivaroxaban trials in VTE treatment, indicating that the use of rivaroxaban offers acceptable treatment results also in routine care. However, we observed significant differences in patient characteristics and management patterns across Switzerland, the United Kingdom, and Germany, limiting direct comparisons of unadjusted outcome event rates between registries., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Background: Catheter-based thrombus removal (CBTR) reduces the risk of moderate to severe post-thrombotic syndrome (PTS) in patients with acute iliofemoral deep vein thrombosis (IF-DVT). However, the impact of concomitant popliteal DVT on clinical and duplex sonographic outcomes is unknown. Patients and methods: In this post-hoc analysis including the entire cohort of the randomized controlled BERNUTIFUL trial (48 patients), we compared clinical (incidence/severity of PTS assessed by Villalta score and revised venous clinical severity scores, rVCSS), disease-specific quality-of-life (QOL, CIVIQ-20 survey) and duplex sonographic outcomes (patency, reflux, post-thrombotic lesions) at 12 months follow-up between patients with IF-DVT with and without concomitant popliteal DVT treated by CBTR. Results: Overall, 48 IF-DVT patients were included (48% men, median age of 50 years), of whom 17 (35%) presented with popliteal DVT. At baseline, patients with popliteal DVT were older, had a higher body mass index and more important leg swelling. At 12 months, freedom from PTS (93% vs 87%, P=0.17), median total Villalta score (1 vs 1.5; P=0.46), rVCSS (2 vs 1.5, P=0.5) and disease-specific QOL (24 points vs 24 points, P=0.72) were similar between patient with and without popliteal DVT, respectively. Duplex sonographic outcomes were similar, except for more frequent popliteal post-thrombotic lesions and reflux (P=0.02) in patients with popliteal DVT. Conclusions: Relevant clinical outcomes 1 year after successful CBTR were favorable, regardless of the presence or absence of concomitant popliteal DVT. However, post-thrombotic popliteal vein lesions and reflux are more frequent in IF-DVT patients with popliteal involvement. Their impact on long-term outcomes remains to be investigated.

Background: COVID-19 is a viral prothrombotic respiratory infection. Heparins exert antithrombotic and anti-inflammatory effects, and might have antiviral properties. We aimed to investigate whether thromboprophylaxis with enoxaparin would prevent untoward hospitalisation and death in symptomatic, but clinically stable outpatients with COVID-19., Methods: OVID was a randomised, open-label, parallel-group, investigator-initiated, phase 3 trial and was done at eight centres in Switzerland and Germany. Outpatients aged 50 years or older with acute COVID-19 were eligible if they presented with respiratory symptoms or body temperature higher than 37·5°C. Eligible participants underwent block-stratified randomisation (by age group 50-70 vs >70 years and by study centre) in a 1:1 ratio to receive either subcutaneous enoxaparin 40 mg once daily for 14 days versus standard of care (no thromboprophylaxis). The primary outcome was a composite of any untoward hospitalisation and all-cause death within 30 days of randomisation. Analysis of the efficacy outcomes was done in the intention-to-treat population. The primary safety outcome was major bleeding. The study was registered in ClinicalTrials.gov (NCT04400799) and has been completed., Findings: At the predefined formal interim analysis for efficacy (50% of total study population), the independent Data Safety Monitoring Board recommended early termination of the trial on the basis of predefined statistical criteria having considered the very low probability of showing superiority of thromboprophylaxis with enoxaparin for the primary outcome under the initial study design assumptions. Between Aug 15, 2020, and Jan 14, 2022, from 3319 participants prescreened, 472 were included in the intention-to-treat population and randomly assigned to receive enoxaparin (n=234) or standard of care (n=238). The median age was 57 years (IQR 53-62) and 217 (46%) were women. The 30-day risk of the primary outcome was similar in participants allocated to receive enoxaparin and in controls (8 [3%] of 234 vs 8 [3%] of 238; adjusted relative risk 0·98; 95% CI 0·37-2·56; p=0·96). All hospitalisations were related to COVID-19. No deaths were reported during the study. No major bleeding events were recorded. Eight serious adverse events were recorded in the enoxaparin group versus nine in the control group., Interpretation: These findings suggest thromboprophylaxis with enoxaparin does not reduce early hospitalisations and deaths among outpatients with symptomatic COVID-19. Futility of the treatment under the initial study design assumptions could not be conclusively assessed owing to under-representation of older patients and consequent low event rates., Funding: SNSF (National Research Programme COVID-19 NRP78: 198352), University Hospital Zurich, University of Zurich, Dr-Ing Georg Pollert (Berlin), Johanna Dürmüller-Bol Foundation., Competing Interests: Declaration of interests SB reports institutional research grants from Concept Medical, Bard, Bentley, Boston Scientific, INARI, Sanofi, and Bayer; and personal fees from Concept Medical, Bayer, Boston Scientific, and INARI. DV, UH, AG, NRS, GC, FM, MR, and TS do not report any conflicts of interest. BG reports non-financial support and funding for an accredited continuing medical education programme from Axonlab, and Thermo Fisher Scientific; personal fees and funding for an accredited continuing medical education programme from Alnylam, Pfizer, and Sanofi; funding for an accredited continuing medical education programme from Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Takeda, Octapharma, SOBI, Janssen, Novo Nordisk, Mitsubishi Pfizer, Tanabe Pharma, outside the submitted work. SVK reports grants or contracts from Bayer AG; consulting fees from Bayer, Daiichi Sankyo, and Boston Scientific; and payment or honoraria from Bayer, INARI Medical, MSD, Pfizer, and Bristol-Myers Squibb. SS reports research grants from Edwards Lifesciences to the institution, research grants from Medtronic to the institution, research grants from Boston Scientific to the institution, research grants from Abbott to the institution, personal fees from Boston Scientific, from Teleflex, from BTG –Boston Scientific outside the submitted work. HRE reports speaker honoraria from Daichi-Sankyo, and Bayer. DS reports employment by Sanofi-Aventis Switzerland. DD reports research support from German Research Foundation, CytoSorbents, Haemonetic; consulting and speaker's fees from Bayer Healthcare, Daiichi Sankyo, LEO Pharma, AstraZeneca, Boston Scientific, and BMS–Pfizer. NK reports institutional research grants from Concept Medical, Bard, Bentley, Boston Scientific, INARI, Sanofi, and Bayer; and personal fees from Concept Medical, Bayer, Boston Scientific, and INARI., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). In confirmatory trials, proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab substantially lowered LDL-C and reduced cardiovascular morbidity and mortality. However, the routine clinical use of alirocumab in Switzerland has not yet been studied., Methods: In this prospective nation-wide cohort study, we aimed to investigate the patient profile and routine clinical efficacy and safety of alirocumab in 207 patients with ASCVD or heterozygous familial hypercholesterolemia and increased LDL-C despite maximally tolerated statin therapy. LDL-C was measured at baseline and after 3-months follow-up., Results: Overall, mean age was 63 ± 11 years, 138 (67%) were men, and 168 (81%) had statin intolerance (SI). Patients with SI had a higher baseline LDL-C (4.3 ± 1.4 vs. 3.3 ± 1.4 mmol/l; p < 0.001) and less frequently ASCVD (71% vs. 95%; p = 0.002). After 3 months of treatment with alirocumab, LDL-C was reduced from 4.1 ± 1.5 to 2.0 ± 1.2 mmol/l (50.5%; p < 0.001). Mean absolute and relative reductions in LDL-C were similar in patients with vs. without SI (2.2 ± 1.2 vs. 1.9 ± 1.3 mmol/l; p = 0.24 and 49.0 vs. 56.6%; p = 0.11, respectively). In total, adverse events were recorded in 25 (12%) patients, with no new safety signals., Conclusions: In routine clinical practice, alirocumab was predominantly used in patients with SI suggesting that the great majority of patients with insufficient LDL-C control who would be candidates for alirocumab are not receiving this therapeutic option in Switzerland. LDL-C lowering was potent and similar in patients with and without SI, replicating the favorable efficacy-safety profile of alirocumab from randomized trials., Competing Interests: IS received speaker fee and research support by Sanofi as well as travel and personal fees by Amgen, Astra Zeneca, Daiichi Sankyo, Menarini, MSD, Recordati, and Servier. TB received research funding to institution by CSEM, Collabree, Medtronic, Roche Diagnostics, and Sanofi as well as travel, speaker, or advisory board fees by Boehringer Ingelheim, Daiichi Sankyo, Novartis, Sanofi, and Servier. SB, TF, and DS are employees of Sanofi, Vernier, Switzerland, and may hold shares and/or stock options in Sanofi. GE received grants or consulting fees to institution from Amgen, Novartis, Sanofi, and Servier, and personal royalties or licenses from UpToDate. No other conflict of interest was reported from the authors regarding the content of this manuscript., (Copyright © 2022 Sudano, Mach, Moccetti, Burkard, Fahe, Delabays, Rickli, Keller, Dopheide, Bodenmann, Fiolka, Ehret and Spirk.)

Importance: Coronary plaques that are prone to rupture and cause adverse cardiac events are characterized by large plaque burden, large lipid content, and thin fibrous caps. Statins can halt the progression of coronary atherosclerosis; however, the effect of the proprotein convertase subtilisin kexin type 9 inhibitor alirocumab added to statin therapy on plaque burden and composition remains largely unknown., Objective: To determine the effects of alirocumab on coronary atherosclerosis using serial multimodality intracoronary imaging in patients with acute myocardial infarction., Design, Setting, and Participants: The PACMAN-AMI double-blind, placebo-controlled, randomized clinical trial (enrollment: May 9, 2017, through October 7, 2020; final follow-up: October 13, 2021) enrolled 300 patients undergoing percutaneous coronary intervention for acute myocardial infarction at 9 academic European hospitals., Interventions: Patients were randomized to receive biweekly subcutaneous alirocumab (150 mg; n = 148) or placebo (n = 152), initiated less than 24 hours after urgent percutaneous coronary intervention of the culprit lesion, for 52 weeks in addition to high-intensity statin therapy (rosuvastatin, 20 mg)., Main Outcomes and Measures: Intravascular ultrasonography (IVUS), near-infrared spectroscopy, and optical coherence tomography were serially performed in the 2 non-infarct-related coronary arteries at baseline and after 52 weeks. The primary efficacy end point was the change in IVUS-derived percent atheroma volume from baseline to week 52. Two powered secondary end points were changes in near-infrared spectroscopy-derived maximum lipid core burden index within 4 mm (higher values indicating greater lipid content) and optical coherence tomography-derived minimal fibrous cap thickness (smaller values indicating thin-capped, vulnerable plaques) from baseline to week 52., Results: Among 300 randomized patients (mean [SD] age, 58.5 [9.7] years; 56 [18.7%] women; mean [SD] low-density lipoprotein cholesterol level, 152.4 [33.8] mg/dL), 265 (88.3%) underwent serial IVUS imaging in 537 arteries. At 52 weeks, mean change in percent atheroma volume was -2.13% with alirocumab vs -0.92% with placebo (difference, -1.21% [95% CI, -1.78% to -0.65%], P < .001). Mean change in maximum lipid core burden index within 4 mm was -79.42 with alirocumab vs -37.60 with placebo (difference, -41.24 [95% CI, -70.71 to -11.77]; P = .006). Mean change in minimal fibrous cap thickness was 62.67 μm with alirocumab vs 33.19 μm with placebo (difference, 29.65 μm [95% CI, 11.75-47.55]; P = .001). Adverse events occurred in 70.7% of patients treated with alirocumab vs 72.8% of patients receiving placebo., Conclusions and Relevance: Among patients with acute myocardial infarction, the addition of subcutaneous biweekly alirocumab, compared with placebo, to high-intensity statin therapy resulted in significantly greater coronary plaque regression in non-infarct-related arteries after 52 weeks. Further research is needed to understand whether alirocumab improves clinical outcomes in this population., Trial Registration: ClinicalTrials.gov Identifier: NCT03067844.

Background: Treatment of pelvic venous disorders (PVD) including pelvic congestion syndrome (PCS) are often delayed due to its varying clinical manifestations. Patients and methods: Patient referral was based on a literature- and personal experience-derived clinical "PCS screening score" (higher score points indicate greater likelihood with a maximum score of 10 points). We studied consecutive women who were (i) referred for vascular assessment and treatment to the University Hospital Zurich (2017-2021), (ii) had a PCS score ≥3 points, (iii) had evidence of obstructive or non-obstructive PVD by duplex sonography or cross-sectional imaging, and (iv) underwent endovascular therapy. The primary outcome was change in symptom severity after endovascular therapy: (i) freedom from symptoms, (ii) improvement with residual symptoms, (iii) no improvement. Results: We included 43 women (mean age 36 years): 81% had previous pregnancy, 19% endometriosis. The median PCS score was 7 (IQR 5-9) points. Chronic lower-abdominal pain was the leading symptom in 86% patients, followed by recurrent leg (9%) and vulvar (5%) varicosities. The main PVD pathologies were ovarian vein insufficiency (61%), internal iliac vein insufficiency (9%), or a combination of both (30%), whereas 42% had a deep venous obstruction of the inferior vena cava, common iliac or left renal veins. Endovascular therapy included ovarian vein embolization (86%), internal iliac vein embolization (9%), and venous stent placement (35%). After a median of 4 (IQR 1-8) months from endovascular treatment, 40 (93%) patients reported improvement of the leading symptom, and 14 (33%) were symptom-free. Complications included re-intervention for stent stenosis (13%, all post-thrombotic), coil-migration into the left renal vein (7%, all retrieved), and transient pelvic sclerotherapy-induced thrombophlebitis (2%). Conclusions: Endovascular therapy following a diagnostic approach, which included a PCS screening tool and non-invasive imaging, appeared to be highly effective and was associated with a low rate of complications.

We aimed to evaluate the impact of age, sex, and their interactions with provoking risk factors for deep vein thrombosis (DVT). In addition, we intended to provide additional insights on risk factors associated with the isolated distal versus proximal presentation of first symptomatic acute DVT, both being characterized by different prognosis. In the present analysis from the SWIss Venous ThromboEmbolism Registry (SWIVTER), we compared demographic and baseline characteristics in patients with isolated distal (n = 184; 35%) versus proximal (n = 346) DVT of the lower limbs without symptomatic pulmonary embolism, and identified factors related with the presenting thrombosis location. In the overall population, mean age was 59 ± 19 years, 266 (50%) were women, 106 (20%) patients had cancer, 86 (16%) recent surgery, and 52 (10%) acute infection/sepsis. In a multivariable analysis, recent surgery [odds ratio (OR) 2.92, 95% confidence interval (CI) 1.80-4.73] was independently associated with a diagnosis of isolated distal DVT, whereas cancer (OR 2.01, 95% CI 1.20-3.35), male sex aged 41 to 75 years (OR 2.21, 95% CI 1.33-3.67), and acute infection/sepsis (OR 2.71, 95% CI 1.29-5.66) with a diagnosis of proximal DVT. In SWIVTER, age, sex, and several provoking risk factors for VTE appeared to be related with the presenting location of first symptomatic DVT. Cancer, male sex, and acute infection/sepsis were associated with a proximal location of DVT, whereas recent surgery was associated with a distal presentation, likely acting as confounders for the association between thrombosis location and prognosis., (© 2021. The Author(s).)

Introduction: Pulmonary embolism (PE) and deep vein thrombosis (DVT), the two clinical manifestations of venous thromboembolism (VTE), constitute a major global burden of cardiovascular disease. They are often referred to as one disease but several patient characteristics, risk factors, real-world treatment, and clinical outcomes may differ substantially between PE and DVT alone., Materials and Methods: We conducted a narrative review of the state-of-the-art literature on the topic of PE and DVT alone using PubMed, Google scholar, and MEDLINE databases and the most established international consensus statement guidelines for the management of VTE, focusing on the recommendations for diagnosis and treatment but also including epidemiological and clinical characteristics of VTE, highlighting similarities and differences between PE and DVT alone., Results: Several patient characteristics, risk factors, clinical manifestations, and outcomes differ substantially between PE versus DVT alone. Nevertheless, recommendations for both diagnosis and treatment are strikingly similar in the current guidelines for the management of DVT and PE, except for the indication for advanced reperfusion therapies., Conclusions: The differences in risk factors, clinical manifestations, and clinical outcomes between patients with PE versus DVT alone are only marginally addressed in the current consensus guidelines. More data is needed allowing proposal of evidence-based adjustments in the diagnostic and therapeutic strategies for these two manifestations of VTE. Tailored risk stratification and individualized management strategies for patients with PE and DVT alone may lead to a better prognosis, less recurrence and complications, and possibly to a gain of quality-adjusted life years in patients with VTE., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The risk for cardiovascular adverse events after acute myocardial infarction (AMI) remains high despite potent medical treatment including low-density lipoprotein cholesterol (LDL-C) lowering with statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies substantially reduce LDL-C when added to statin. Alirocumab, a monoclonal antibody to PCSK9, reduces major adverse cardiovascular events after AMI. The effects of alirocumab on coronary atherosclerosis including plaque burden, plaque composition and fibrous cap thickness in patients presenting with AMI remains unknown., Aims: To determine the effect of LDL-C lowering with alirocumab on top of high-intensity statin therapy on intravascular ultrasound (IVUS)-derived percent atheroma volume (PAV), near-infrared spectroscopy (NIRS)-derived maximum lipid core burden index within 4 mm (maxLCBI 4 mm ) and optical coherence tomography (OCT)-derived fibrous cap thickness (FCT) in patients with AMI., Methods: In this multicenter, double-blind, placebo-controlled trial, 300 patients with AMI (ST-elevation or non-ST-elevation myocardial infarction) were randomly assigned to receive either biweekly subcutaneous alirocumab (150 mg) or placebo beginning <24 hours after the acute event as add-on therapy to rosuvastatin 20 mg. Patients undergo serial IVUS, NIRS and OCT in the two non-infarct related arteries at baseline (at the time of treatment of the culprit lesion) and at 52 weeks. The primary endpoint, change in IVUS-derived PAV, and the powered secondary endpoints, change in NIRS-derived maxLCBI 4 mm , and OCT-derived minimal FCT, will be assessed 52 weeks post randomization., Summary: The PACMAN-AMI trial will determine the effect of alirocumab on top of high-intensity statin therapy on high-risk coronary plaque characteristics as assessed by serial, multimodality intracoronary imaging in patients presenting with AMI., Clinical Trial Registration: NCT03067844., (Copyright © 2021. Published by Elsevier Inc.)

Aims: We assessed morphological features of near-infrared spectroscopy (NIRS)-detected lipid-rich plaques (LRPs) by using optical coherence tomography (OCT) and intravascular ultrasound (IVUS)., Methods and Results: IVUS-NIRS and OCT were performed in the two non-infarct-related arteries (non-IRAs) in patients undergoing percutaneous coronary intervention for treatment of an acute coronary syndrome. A lesion was defined as the 4 mm segment with the maximum amount of lipid core burden index (maxLCBI4mm) of each LRP detected by NIRS. We divided the lesions into three groups based on the maxLCBI4mm value: <250, 250-399, and ≥400. OCT analysis and IVUS analysis were performed blinded for NIRS. We measured fibrous cap thickness (FCT) by using a semi-automated method. A total of 104 patients underwent multimodality imaging of 209 non-IRAs. NIRS detected 299 LRPs. Of those, 41% showed a maxLCBI4mm <250, 39% a maxLCBI4mm 251-399, and 19% a maxLCBI4mm ≥400. LRPs with a maxLCBI4mm ≥400, as compared with LRPs with a maxLCBI4mm 250-399 and <250, were more frequently thin-cap fibroatheroma (TCFA) (42.1% vs. 5.1% and 0.8%; P < 0.001) with a smaller minimum FCT (80 μm vs. 110 μm and 120 μm; P < 0.001); a higher IVUS-derived percent atheroma volume (53% vs. 53% and 44%; P < 0.001) and a higher remodelling index (1.08 vs. 1.02 and 1.01; P < 0.001). MaxLCBI4mm correlated with OCT-derived FCT (r = 0.404; P < 0.001) and was the best predictor for TCFA with an optimal cut-off value of 401 (area under the curve = 0.882; P < 0.001)., Conclusion: LRPs with increasing maxLCBI4mm exhibit OCT and IVUS features of presumed plaque vulnerability including TCFA morphology, increased plaque burden, and positive remodelling., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Introduction: Pulmonary embolism (PE) has not been accounted for as a cause of death contributing to cause-specific mortality in global reports., Methods: We analyzed global PE-related mortality by focusing on the latest year available for each member state in the World Health Organization (WHO) mortality database, which provides age-sex-specific aggregated mortality data transmitted by national authorities for each underlying cause of death. PE-related deaths were defined by International Classification of Diseases, Tenth Revision codes for acute PE or nonfatal manifestations of venous thromboembolism (VTE). The 2001 WHO standard population served for standardization., Results: We obtained data from 123 countries covering a total population of 2 602 561 422. Overall, 50 (40.6%) were European, 39 (31.7%) American, 13 (10.6%) Eastern Mediterranean, 13 (10.6%) Western Pacific, 3 (2.4%) Southeast Asian, and 2 (1.6%) African. Of 116 countries classifiable according to population income, 57 (49.1%) were high income, 42 (36.2%) upper-middle income, 14 (12.1%) lower-middle income, and 3 (2.6%) low income. A total of 18 726 382 deaths were recorded, of which 86 930 (0.46%) were attributed to PE. PE-related mortality rate increased with age in most countries. The reporting of PE-related deaths was heterogeneous, with an age-standardized mortality rate ranging from 0 to 24 deaths per 100 000 population-years. Income status only partially explained this heterogeneity., Conclusions: Reporting of PE-related mortality in official national vital registration was characterized by extreme heterogeneity across countries. These findings mandate enhanced efforts toward systematic and uniform coverage of PE-related mortality and provides a case for full recognition of PE and VTE as a primary cause of death., (© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Objective:  In patients with cancer-associated venous thromboembolism (VTE), the risk of recurrence is similar after incidental and symptomatic events. It is unknown whether the same applies to incidental VTE not associated with cancer., Methods and Results:  We compared baseline characteristics, anticoagulation therapy, all-cause mortality, and VTE recurrence rates at 90 days between patients with incidental ( n  = 131; 52% without cancer) and symptomatic ( n  = 1,931) VTE included in the SWIss Venous ThromboEmbolism Registry (SWIVTER). After incidental VTE, 114 (87%) patients received anticoagulation therapy for at least 3 months. The mortality rate was 9.2% after incidental and 8.4% after symptomatic VTE for hazard ratio (HR) 1.10 (95% confidence interval [CI] 0.49-2.50). After adjustment for competing risk of death, recurrence rate was 3.1 versus 2.8%, respectively, for sub-HR 1.07 (95% CI 0.39-2.93). These results were consistent among cancer (mortality: 15.9% vs. 12.6%; HR 1.32, 95% CI 0.67-2.59; recurrence: 4.8% vs. 4.7%; HR 1.02, 95% CI 0.30-3.42) and noncancer patients (mortality: 2.9% vs. 2.1%; HR 1.37, 95% CI 0.33-5.73; recurrence: 1.5% vs. 2.3%; HR 0.63, 95% CI 0.09-4.58). Patients with incidental VTE who received anticoagulation therapy for at least 3 months had lower mortality (4% vs. 41%) and recurrence rate (1% vs. 18%) compared with those who did not., Conclusion:  In SWIVTER, more than half of incidental VTE events occurred in noncancer patients who often received anticoagulation therapy. Among noncancer patients, early mortality and recurrence rates were similar after incidental versus symptomatic VTE. Our findings suggest that anticoagulation therapy for incidental VTE may be beneficial regardless of the presence of cancer., Competing Interests: D.S. is an employee of Sanofi-Aventis (Suisse) SA, Vernier, Switzerland. S.B. reports personal fees from BTG Pharmaceuticals and Leo Pharma, personal fees and nonfinancial support from Bayer HealthCare, and nonfinancial support from Daiichi-Sankyo, outside the submitted work. J.H.B. reports grants from the Swiss National Science Foundation and the Swiss Heart Foundation, grants and personal fees from Boehringer Ingelheim, Pfizer, Bayer, and Daiichi-Sankyo, outside the submitted work. R.P.E. reports personal fees from Bayer, Daiichi-Sankyo, and Sanofi-Aventis, outside the submitted work. W.K. reports personal fees and nonfinancial support from Bayer, Pfizer, Shire/Takeda, Roche, Daiichi-Sankyo, and Novo Nordisk, outside the submitted work. M.H. reports personal fees from Sanofi-Aventis, Daiichi-Sankyo, and Bayer, outside the submitted work. N.K. reports personal fees from Bayer, Boston Scientific, Optimed, Bard, and BTG, outside the submitted work., (Thieme. All rights reserved.)

Background: Angioplasty with stent placement is a therapeutic option for patients with acute thrombotic, postthrombotic, and nonthrombotic obstruction of the iliofemoral veins or inferior vena cava. Previous studies of steel-alloy stents described variable patency rate across indications., Methods: The prospective Swiss Venous Stent Registry includes patients treated with self-expandable nitinol stents for deep venous obstruction. Routine follow-up visits include serial duplex ultrasound for stent patency assessment. The primary outcome was primary stent patency. The secondary outcome was venous thromboembolisms. We studied the rate of stent occlusion and potentially contributing factors., Results: We included 379 patients: 160 with acute thrombotic, 193 with postthrombotic, and 26 with nonthrombotic deep vein obstruction. The mean age was 46±18 years; 55% were women. The cumulative 3-year primary patency rate was 80.5% (95% CI, 73.0%-88.0%) for acute thrombotic, 59.2% (95% CI, 50.4%-68.0%) for postthrombotic, and 100% for nonthrombotic obstruction (log-rank, P <0.0001). Annualized rates of stent occlusion or venous thromboembolism were 7.8 (acute thrombotic), 15.0 (postthrombotic), and 0 (nonthrombotic) events/100 patient-years. In a multivariable Cox regression model, postthrombotic femoral veins at baseline (hazard ratio, 2.64 [95% CI, 1.53-4.56]) and the number of stents (hazard ratio, 1.22 [95% CI, 1.06-1.40]) were associated with stent occlusion after conditioning for age, sex, and clinically relevant factors., Conclusions: The rate of stent occlusion (patency loss) and venous thromboembolism varies substantially across indications, also with dedicated venous nitinol stents. Patients with postthrombotic femoral veins and those who received multiple stents were characterized by the highest risk. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT02433054.

Objective: Duplex ultrasound (DUS) is used for routine surveillance of stents in iliocaval veins, but direct visualisation is often challenging. Duplex ultrasound criteria for detecting venous stent obstruction (VSO) have not been defined to date., Methods: A nested case control study of 120 patients (42 ± 17 years, 53% women, mean 2.7 ± 1.8 stents) was performed, and the performance of various duplex parameters for detecting VSO (defined as > 50% lumen diameter reduction or occlusion) was tested, confirmed by biplane venography or intravascular ultrasound (IVUS). Forty patients with VSO (25 with stent occlusion, 15 with >50% in stent stenosis) were matched to 80 control patients by age, gender and index diagnosis who fulfilled the following criteria: (1) ongoing symptom control (Villalta score < 5), (2) good image quality of entire stent segment, (3) spontaneous colour Doppler signal > 50% of lumen in entire stent segment, (4) at least two DUS where the baseline DUS was obtained within 24 h after successful venous intervention., Results: The best test was the combination of peak flow velocity and flow pattern analysis at the stent inlet. A peak flow velocity >10 cm/s and a flow pattern spontaneously modulated by respiration ruled out VSO with a specificity of 93.7% (95% CI 86.0%-97.3%). A peak flow velocity ≤10 cm/s or any Doppler flow pattern other than spontaneously modulated by respiration was 92.1% (95% CI 79.2%-97.3%) sensitive to detect VSO., Conclusion: The combination of peak flow velocity and analysis of Doppler flow pattern at the stent inlet is accurate to diagnose or rule out stent occlusion. Indirect criteria should always be combined with direct visualisation of iliocaval stents since those may be less sensitive for detecting stent stenosis., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: Lowering blood pressure (BP) leads to reduced risk of stroke, myocardial infarction, and cardiovascular mortality. Single-pill combination therapies may deliver better BP control than increasing the dose of monotherapies or using more drugs separately. Objectives: The aim of the present observational study was to investigate the real-life use and the effect of first line or replacement single-pill combination therapies containing irbesartan and hydrochlorothiazide (HCTZ) on systolic BP (SBP) control rate in patients with hypertension. Methods: Overall, 780 patients with moderate or severe hypertension either untreated (289; 37%) or uncontrolled (491; 63%) with previous therapy were included in the "First Line CombinAtion Therapy in the Treatment of Stage II and III Hypertension" (FLASH) prospective Swiss national-wide cohort study. All recruited patients received single-pill antihypertensive combination therapy containing HCTZ and irbesartan. BP was measured at baseline and after 8-weeks follow-up according to guidelines. Results: Mean reductions in office systolic/diastolic BP (SBP/DBP) were 23.7 ± 13.7/11.7 ± 8.5 mmHg, with reductions of 26.9 ± 14.1/13.0 ± 8.8 mmHg or 21.8 ± 13.1/11.0 ± 8.3 mmHg when the single-pill combination of irbesartan/HCTZ was given as first line or replacement treatment, respectively ( p < 0.001 for differences between first line and replacement treatment in both SBP and DBP). The guidelines-recommended goals were reached in 368 (47%), 492 (63%), and 312 (40%) patients for SBP, DBP, and SBP/DBP, respectively. The SBP control rate was higher when the combination was used as first line treatment (52 vs. 44%; p = 0.043). Overall, 145 adverse events were recorded; hypotension in 12 (1.5%) cases, hypokalaemia in 9 (1.2%), and hyperkalaemia in 3 (0.4%). Conclusions: The single-pill combination of irbesartan/HCTZ was well-tolerated and achieved substantial reductions in both systolic and diastolic BP. The SBP control rate was greater when the combination was prescribed as first line treatment as suggested by recent ESC/ESH guidelines., (Copyright © 2020 Spirk, Noll, Burnier, Rimoldi, Noll and Sudano.)

Background:  Patients with postthrombotic syndrome (PTS) treated with stents are at risk of stent thrombosis (ST). The incidence of ST in the presence and absence of anticoagulation therapy (AT) is unknown. Risk factors are not well understood., Patients and Methods:  From the prospective Swiss Venous Stent registry, we conducted a subgroup analysis of 136 consecutive patients with PTS. Incidence of ST was estimated from duplex ultrasound or venography, and reported for the time on and off AT. Baseline, procedural, and follow-up data were evaluated to identify factors associated with ST., Results:  Median follow-up was 20 (interquartile range [IQR] 9-40) months. AT was stopped in 43 (32%) patients after 12 (IQR 6-14) months. Cumulative incidence of ST was 13.7% (95% confidence interval [CI] 7.8-19.6%) and 21.2% (95% CI 13.2-29.2%) during the first 6 and 36 months, respectively. The time-adjusted incidence rate was 11.2 (95% CI 7.7-16.2) events per 100 patient-years, 11.3 (95% CI 7.3-17.3) for the period on, and 11.2 (95% CI 5.3-23.6) for the period off AT. May-Thurner syndrome (MTS) was associated with decreased incidence of ST (hazard ratio [HR] 0.37, 95% CI 0.15-0.91), whereas age < 40 years (HR 2.26, 95% CI 1.03-4.94), stents below the common femoral vein (HR 3.03, 95% CI 1.28-7.19), and postthrombotic inflow veins (HR 2.92, 95% CI 1.36-6.25) were associated with increased incidence., Conclusion:  The 6-month incidence of ST was considerably high. Beyond 6 months, consecutive annual incidence rates persisted at 4.1 and 3.4% per year thereafter. Patients with higher incidence of ST were younger, had stents below the common femoral vein, postthrombotic leg inflow veins, and less often MTS. Incidence rates for the period on and off AT must be interpreted with caution., Clinical Trial Registration:  The study is registered on the National Institutes of Health Web site (ClinicalTrials.gov; identifier NCT02433054)., Competing Interests: D.S. is an employee at Sanofi-Aventis (Suisse). R.P.E. is a consultant for EKOS Corp and has received speaker honoraria from Bayer, Sanofi-Aventis, Bard, and Boston Scientific. S.B. reports personal fees from BTG/EKOS, nonfinancial support from Bayer HealthCare, nonfinancial support from Daiichi Sankyo, outside the submitted work. N.K. reports consultant and speaker honoraria from Bayer, Boston scientific, Optimed, Bard, and BTG. D.S. reports personal fees from Sanofi-Aventis (Suisse) SA, Vernier, Switzerland, outside the submitted work. R.P.E. is a consultant for EKOS Corp and has received speaker honoraria from Bayer, Sanofi-Aventis, Bard, and Boston Scientific. S.B. reports personal fees from BTG/EKOS, nonfinancial support from Bayer HealthCare, nonfinancial support from Daiichi Sankyo, outside the submitted work. N.K. reports personal fees from Bayer, personal fees from Boston scientific, personal fees from Optimed, personal fees from Bard, personal fees from BTG, outside the submitted work. All other authors report no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Renal impairment (RI) has increased substantially over the last decades. In the absence of data from confirmatory research, real-life data on anticoagulation treatment and clinical outcomes of venous thromboembolism (VTE) in patients with RI are needed. In the SWIss Venous ThromboEmbolism Registry (SWIVTER), 2,062 consecutive patients with objectively confirmed VTE were enrolled. In the present analysis, we compared characteristics, initial and maintenance anticoagulation, and adjusted 90-day clinical outcomes of those with (defined as estimated creatinine clearance < 30 mL/min) and without severe RI. Overall, 240 (12%) patients had severe RI; they were older, and more frequently had chronic and acute comorbidities. VTE severity was similar between patients with and without severe RI. Initial anticoagulation in patients with severe RI was more often performed with unfractionated heparin (44 vs. 24%), and less often with low-molecular-weight heparin (LMWH) (52 vs. 61%) and direct oral anticoagulants (DOACs; 4 vs. 12%). Maintenance anticoagulation in patients with severe RI was more frequently managed with vitamin K antagonists (70 vs. 60%) and less frequently with DOAC (12 vs. 21%). Severe RI was associated with increased risk of 90-day mortality (9.2 vs. 4.2%, hazard ratio [HR]: 2.27, 95% confidence interval [CI]: 1.41-3.65), but with similar risk of recurrent VTE (3.3 vs. 2.8%, HR: 1.19, 95% CI: 0.57-2.52) and major bleeding (2.1 vs. 2.0%, HR: 1.05, 95% CI: 0.41-2.68). In patients with severe RI, the use of LMWH versus any other treatment was associated with reduced mortality (HR: 0.37; 95% CI: 0.14-0.94; p  = 0.036) and similar rate of major bleeding (HR: 0.59, 95% CI: 0.17-2.00; p  = 0.39). Acute or chronic comorbidities rather than VTE severity or recurrence may explain increased early mortality in patients with severe RI. The higher rate of VTE recurrence, specifically fatal events, than major bleeding reinforces the need for effective anticoagulation in VTE patients with severe RI., Competing Interests: D.S. is an employee of Sanofi-Aventis (Suisse) SA, Vernier, Switzerland. J.H.B. reports grants from the Swiss National Science Foundation and the Swiss Heart Foundation, grants and personal fees from Boehringer Ingelheim, Pfizer, Bayer, and Daiichi Sankyo, outside the submitted work. R.P.E. reports personal fees from Bayer and Sanofi-Aventis, outside the submitted work. W.K. reports personal fees and nonfinancial support from Bayer, Pfizer, Shire/Takeda, Roche, Daiichi Sankyo, and Novo Nordisk, outside the submitted work. M.H. reports personal fees from Sanofi-Aventis, Daiichi Sankyo, and Bayer, outside the submitted work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: The optimal duration of anticoagulation therapy (AT) following catheter-based therapy of acute iliofemoral deep vein thrombosis (IFDVT) with stent placement is unknown. Theoretically, resolving the underlying obstructive iliac vein lesion by a stent may eliminate the main trigger for recurrence, the post-thrombotic syndrome (PTS), and the need for extended-duration AT. Patients and methods: From 113 patients with acute IFDVT who underwent endovascular thrombus removal and stent placement, we compared patency rates and clinical outcomes between 58 patients on limited-duration AT (3-12 month) and 55 patients on extended-duration AT (> 12 months). Results: Mean follow-up duration was 26 ± 18 (range 3-77) months; it was 24 ± 18 (range 3-69) months after cessation of AT in the limited-duration AT group. In comparison to patients with extended-duration AT, patients with limited-duration AT were younger (38 versus 54 years; p < 0.001), more often female (74 % versus 49 %; p = 0.01), and had less often prior venous thromboembolism (VTE) (9 % versus 35 %; p = 0.001). May-Thurner syndrome was more frequent in the limited-duration AT group (66 % versus 38 %; p = 0.004). Overall, primary and secondary patency rates at 24 months were 80 % (95 % CI, 70-87 %) and 95 % (95 % CI, 88-98 %), respectively, with no difference between the groups. Overall, 17 (15 %) patients developed recurrent VTE, of which 14 (82 %) events were thrombotic stent occlusions, and 13 (76 %) events occurred during AT. In the limited-duration AT group, 98 % patients were free from the PTS at two years with a VTE recurrence rate of 3.5 per 100 patient years after cessation of AT. Conclusions: In selected patients with acute IFDVT and patent venous stent, particularly in younger and otherwise healthy patients with May-Thurner syndrome, it appears to be safe to discontinue AT 3-12 months after endovascular treatment. Clinical Trial Registration: The study is registered on the National Institutes of Health website (ClinicalTrials.gov; identifier NCT02433054).

In Switzerland, Pharmaceutical Medicine has existed as one of 46 physician specialties accredited by the Federal Office of Public Health for more than 20 years. As a medical-scientific discipline, our goal is to enable best possible therapeutic coverage for the benefit of patients and society through a medical need-based development and optimal use of medicinal products. The role of the specialist in Pharmaceutical Medicine is to closely collaborate with various stakeholders of the healthcare system in the context of the discovery, research, development and approval of new medicinal products, as well as safe and effective use of new and established medicinal products in daily clinical practice. The post-graduate training consists of 2 years of patient-related clinical work, followed by 3 years of vocational training at certified training centers in Pharmaceutical Medicine. This also includes completion of an academic post-graduate diploma in Pharmaceutical Medicine (30 ECTS) according to the IFAPP/PharmaTrain syllabus and a 1 day board exam. As part of an ongoing revision of the training curriculum, we are developing a Swiss Catalog of Core Competencies in Pharmaceutical Medicine (SC 3 -PM), based on the IFAPP competency framework for drug development specialists in industry. In this article we discuss how we adapt the scope of the IFAPP competency framework to better reflect such roles in academic institutions or regulatory bodies in Switzerland.

Background: The optimal anticoagulant following catheter-based therapy of acute iliofemoral deep vein thrombosis (IFDVT) is unknown., Methods: From the Swiss Venous Stent registry, an ongoing prospective cohort study, we performed a subgroup analysis of patients with acute IFDVT who underwent catheter-based early thrombus removal followed by nitinol stent placement. Duplex ultrasound and Villalta scores were used to determine patency rates and incidence of the post-thrombotic syndrome (PTS) in patients treated with either rivaroxaban (n = 73) or a vitamin K-antagonist (VKA; n = 38) for a minimum duration of 3 months., Results: Mean follow-up duration was 24 ± 19 months (range 3 to 77 months). Anticoagulation therapy was time-limited (3 to 12 months) in 56% of patients (47% in the rivaroxaban group and 58% in the VKA group, p = 0.26), with shorter mean duration of anticoagulation in the rivaroxaban group (180 ± 98 days versus 284 ± 199 days, p = 0.01). Overall, primary and secondary patency rates at 24 months were 82% (95%CI, 71-89%) and 95% (95%CI, 87-98%), respectively, with no difference between the rivaroxaban (87% [95%CI, 76-94%] and 95% [95%CI, 85-98%]) and the VKA group (72% [95%CI, 52-86%] and 94% [95%CI, 78-99%]; p > 0.10 for both). Overall, 86 (86%) patients were free from PTS at latest follow-up, with no difference between the rivaroxaban and the VKA groups (57 [85%] versus 29 [88%]; p = 0.76). Two major bleeding complications (1 in each group) occurred in the peri-interventional period, without any major bleeding thereafter., Conclusions: In patients with acute IFDVT treated with catheter-based early thrombus removal and venous stent placement, the effectiveness and safety of rivaroxaban and VKA appear to be similar., Clinical Trial Registration: The study is registered on the National Institutes of Health website (ClinicalTrials.gov; identifier NCT02433054)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and Aims: In Switzerland, the prevalence of familial hypercholesterolemia (FH) due to pathogenic apolipoprotein B-100 gene (APOB) variants was known, but not the prevalence of FH due to pathogenic low-density lipoprotein-receptor gene (LDLR) variants. Phenotypic differences (LDLR versus APOB) might affect the diagnostic value of the Dutch Lipid Clinic Network (DLCN) score and Simon Broome Diagnostic Criteria (SBDC)., Methods: A total of 2734 Swiss subjects were investigated, 2221 unselected subjects from three representative population surveys for estimation of the prevalence (LDLR variants), and 513 subjects from the DIAgnosis and Management Of familial hypercholesterolemia in a Nationwide Design (DIAMOND-FH) study for comparisons of phenotypic characteristics (LDLRversusAPOB variants), diagnostic values of clinical scores, and cardiovascular outcome., Results: In 7 of 2221 individuals, FH (LDLR) was diagnosed (prevalence of FH due to LDLR variants: 1/317, prevalence of FH due to both LDLR and APOB variants: 1/125 to 1/135). In FH (APOB) patients under 35 years of age, mean total cholesterol (TC) was <8.5 mmoL/L but increased above 35. In FH (LDLR), TC was >8.5 mmoL/L in all age groups. This difference was crucial for the diagnosis of FH and resulted in a significantly lower sensitivity of clinical scores in FH (APOB) (DLCN: 13.8%, p < 0.0001; SBDC: 22.5%, p = 0.005). Thus, both scores were not useful for the definite diagnosis of FH due to APOB variants. Regarding the cardiovascular outcome, no differences (LDLR versus APOB) were found above 60 years. In countries with high percentages of FH due to APOB variants, cascade screening and molecular testing appear to be much more cost-effective., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Occlusion of the inferior vena cava (IVC) often causes venous claudication, leg swelling, or skin changes. We hypothesized that the outcome of nitinol stents for endovascular reconstruction of the IVC is similar to the outcome reported for steel alloy stents., Methods: From the prospective Bern Venous Stent Registry, we investigated technical success, patency rates, and clinical outcome in consecutive patients with endovascular IVC reconstruction. During routine follow-up visits, stent patency was assessed by duplex ultrasound. Clinical outcomes were evaluated using the Bozkaya score, Villalta score, and revised Venous Clinical Severity Score., Results: Of the 62 patients (mean age, 46 ± 18 years), 33 (53%) patients were treated for the post-thrombotic syndrome, 17 (27%) for acute thrombosis, and 12 (19%) for nonthrombotic IVC occlusion. Technical success was achieved in 61 (98%) patients, with a mean of 4.5 ± 1.9 stents (iliac kissing stents in 84%). During follow-up (mean, 21 months), 22 (36%) underwent endovascular reintervention for symptomatic stent stenosis (13 [21%] with complete stent occlusion). Primary, primary assisted, and secondary patency rates at 24 months were 57% (95% confidence interval [CI], 50%-73%), 76% (95% CI, 65%-86%), and 87% (95% CI, 80%-95%), respectively. None developed new ulcers, and all eight patients with venous ulcers at baseline had complete healing. Twenty-nine (48%) patients showed significant clinical improvement, and another 26 (43%) were free from any symptoms or signs of venous hypertension. Patients with post-thrombotic venographic changes of the femoral veins at baseline or a history of thrombosis were more likely to lose primary patency compared with patients with normal leg inflow veins and no history of thrombosis (19 [48%] vs 3 [16%]; P = .02)., Conclusions: The clinical outcome of endovascular reconstruction of the IVC with nitinol stents was favorable. However, approximately one-third of the patients required reintervention to maintain stent patency, most likely because of the impaired venous inflow., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Improved thromboprophylaxis for acutely ill medical patients relies on valid predictions of thrombotic risks. Our aim was to compare the performance of the Improve and Geneva clinical risk assessment models (RAMs), and to simplify the current Geneva RAM., Methods: Medical inpatients from eight Swiss hospitals were prospectively followed during 90 days, for symptomatic venous thromboembolism (VTE) or VTE-related death. We compared discriminative performance and calibration of the RAMs, using time-to-event methods with competing risk modelling of non-VTE death., Results: In 1,478 patients, the 90-day VTE cumulative incidence was 1.6%. Discrimination of the Improve and Geneva RAM was similar, with a 30-day AUC (areas under the curve) of 0.78 (95% CI [confidence interval]: 0.65-0.92) and 0.81 (0.73-0.89), respectively. According to the Improve RAM, 68% of participants were at low risk (0.8% VTE at 90 days), and 32% were at high risk (4.7% VTE), with a sensitivity of 73%. According to the Geneva RAM, 35% were at low risk (0.6% VTE) and 65% were at high risk (2.8% VTE), with a sensitivity of 90%. Among patients without thromboprophylaxis, the sensitivity was numerically greater in the Geneva RAM (85%) than in the Improve RAM (54%). We derived a simplified Geneva RAM with comparable discrimination and calibration as the original Geneva RAM., Conclusions: We found comparably good discrimination of the Improve and Geneva RAMs. The Improve RAM classified more patients as low risk, but with possibly lower sensitivity and greater VTE risks, suggesting that a lower threshold for low risk (<2) should be used. The simplified Geneva RAM may represent an alternative to the Geneva RAM with enhanced usability., Competing Interests: Conflict of Interest: Dr. David Spirk is an employee of Sanofi-Aventis (Suisse) SA, Vernier, Switzerland., (Schattauer GmbH Stuttgart.)

Background/aims: Despite availability of a broad spectrum of blood pressure (BP)-lowering drugs many hypertensive patients do not attain BP goals. We aimed to evaluate the influence of home blood pressure monitoring (HBPM) on patient's awareness and attainment of BP goals under antihypertensive treatment with irbesartan alone or in combination with hydro-chlorothiazide., Methods: In total, 1,268 patients with arterial hypertension were enrolled in the Factors Influencing Results in anti-hypertenSive Treatment (FIRST) study by 348 general practitioners and internal medicine specialists across Switzerland. Patients selected for HBPM received detailed information and training on BP self-management. The study endpoints included patient's awareness and attainment of BP goals, and the efficacy and tolerability of antihypertensive treatment at 3 months., Results: Overall, the mean age was 61±13 years and 616 (49%) were women. The mean systolic/diastolic BP was 161±17/96±11 mmHg, and 239 (19%) patients had diabetes mellitus. 758 (60%) patients were instructed to use HBPM. Both the proportion of patients aware of their BP goals (81% vs. 70%; p< 0.001) and the percentage of patients reaching their BP goal (64% vs. 57%; p=0.028) were higher in those with vs. without HBPM. The mean reduction in systolic/diastolic BP was 23.8/13.2 mmHg. Only 35 (3.0%) patients discontinued antihypertensive therapy., Conclusion: In a large Swiss cohort of patients with arterial hypertension, information and training on BP self-measurement and direct involvement of patients by using HBPM led to improvement in BP control. Treatment with irbesartan alone or in combination with hydrochlorothiazide was well tolerated and markedly reduced BP., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Competing Interests: Conflict of Interest: Dr. Spirk is an employee of Sanofi-Aventis (Suisse) SA, Vernier, Switzerland.

Essentials Venous thromboembolism (VTE) prophylaxis in hospitalized medical patients remains inconsistent. We implemented an electronic alert system featuring a validated risk assessment model for VTE. In this randomized controlled study, the e-alert system did not improve VTE prophylaxis. Many electronic alerts were ignored by ordering physicians., Summary: Background The use of thromboprophylaxis among acutely ill hospitalized medical patients remains inconsistent. Objective To improve thromboprophylaxis use by implementing a computer-based alert system combined with a Geneva Risk Score calculation tool in the electronic patient chart and order entry system. Patients/Methods Consecutive patients admitted to the general internal medicine wards of the University Hospital Bern, Switzerland were randomized to the alert group, in which an alert and the Geneva Risk Score calculation tool was issued in the electronic patient chart, or to the control group, in which no alert was issued. The primary endpoint was the rate of appropriate thromboprophylaxis during hospital stay. Results Overall, 1593 patients (alert group, 804; control group, 789) were eligible for analysis. The median age was 67 years (interquartile range, 53-79 years) and 47% were female. Appropriate thromboprophylaxis was administered to 536 (66.7%) patients from the alert group and to 526 (66.7%) patients from the control group. Among the 804 patients from the alert group, a total of 446 (55.5%) either had no score calculation by the physician in charge (n = 348) or had a calculated score result that was inconsistent with information from the patient chart (n = 98). Appropriate thromboprophylaxis was less often administered to patients with no score or an inconsistent score result than to 358 patients with a consistent score result (62.6% versus 71.8%). Conclusions The electronic alert (e-alert) system did not improve appropriate thromboprophylaxis, most likely because many e-alerts were ignored by ordering physicians. The use of appropriate thromboprophylaxis in the control group was higher than expected., (© 2017 International Society on Thrombosis and Haemostasis.)

Essentials Acute iliofemoral deep vein thrombosis can be treated with catheter-directed thrombolysis (CDT). We performed a randomized trial comparing conventional CDT versus ultrasound-assisted CDT (USAT). Clinical and duplex sonographic outcomes at 12 months were similar in the CDT and USAT groups. In both groups, incidence of postthrombotic syndrome was very low with good quality of life., Summary: Background In patients with acute iliofemoral deep vein thrombosis (IFDVT), catheter-directed thrombolysis (CDT) aims to prevent the postthrombotic syndrome (PTS). Adding intravascular high-frequency, low-power ultrasound energy to CDT does not seem to improve the immediate thrombolysis results but its impact on clinical outcomes at 12 months is not known. Patients/Methods In this randomized-controlled trial, 48 patients (mean age 50 ± 21 years; 52% women) with acute IFDVT were randomized to conventional CDT (n = 24) or ultrasound-assisted CDT (USAT; n = 24). In both groups, a fixed-dose thrombolysis regimen (20 mg r-tPA over 15 h) was used, followed by routine stenting of residual venous obstruction. At 12 months, PTS and venous disease severity (Villalta score and revised Venous Clinical Severity Score [rVCSS]), disease-specific quality of live (QOL; CIVIQ-20) and duplex-sonographic outcomes were assessed. Results Among the 45 surviving patients, 40 (89%; 95% confidence interval [CI] 76-96%) patients were free from PTS (defined as Villalta score < 5 points; 83%, 95% CI 61-95% in the USAT and 96%, 95% CI 77-100% in the CDT group), with a similar mean total Villalta score of 2.3 ± 2.9 vs. 1.7 ± 1.6, and a mean total rVCSS of 3.0 ± 3.5 vs. 2.7 ± 2.9 in the USAT and the CDT groups, respectively. Both groups had good disease-specific QOL with a CIVIQ-20 score of 29.4 ± 11.8 vs. 26.1 ± 7.8, respectively. Primary (100% vs. 92%) and secondary (100% vs. 96%) iliofemoral patency rates and presence of femoro-popliteal venous reflux (39% vs. 33%) were similar in both groups. Conclusion The addition of intravascular ultrasound energy to conventional CDT for the treatment of acute IFDVT did not have any impact on relevant clinical or duplex sonographic outcomes, which were favorable in both study groups. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier:NCT01482273., (© 2017 International Society on Thrombosis and Haemostasis.)

Observational data show a consistent association between elevated low density lipoproteins (LDL-C) and cardiovascular disease (CVD). Reduction of LDL-C reduces the risk of CVD as has been shown by many trials. Statins are currently the most effective drugs for lowering LDL-C, but can present side effects which might limit the prescribed dosage and prevent patients from reaching the recommended LDL levels. Although treated with statins important residual cardiovascular event risk remains in patients in primary and secondary prevention for CVD. The discovery of protein convertase subtilisin kexin 9 antibodies is a very promising new hypolipidemic treatment and the aim of this review is to explain their mechanism of action and to discuss safety and efficacy results of some phase III studies., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Although the use of thromboprophylaxis is recommended for acutely ill medical patients at increased risk of venous thromboembolism (VTE), it remains unclear which risk assessment model (RAM) should be routinely used to identify at-risk patients requiring thromboprophylaxis. We therefore aimed to describe existing RAMs, and to compare these tools in terms of validity and applicability for clinical decision-making. We performed a comprehensive systematic search in MEDLINE from the date of initiation until May 2016 for studies in acutely ill medical patients investigating validity of RAMs for VTE. Two reviewers independently screened the title, abstract, and full text, and evaluated the characteristics of studies, and the composition, evidence of validation, and results on validity of the RAMs. We included 11 studies assessing eight RAMs: 4-Element RAM, Caprini RAM, a full logistic model, Geneva risk score, IMPROVE-RAM, Kucher Model, a "Multivariable Model", and Padua Prediction Score. The 4-Element RAM, IMPROVE-RAM, Multivariable Model, and full logistic model had derivation by identifying factors with predictive power. The other four RAMs were empirically generated based on consensus guidelines, published data, and clinical expertise. The Kucher Model, the Padua Prediction Score, the Geneva Risk Score and the IMPROVE-RAM underwent multicenter external validation. The Kucher Model, the Padua Prediction Score, and the Geneva Risk Score improved rates of thromboprophylaxis or clinical outcomes. In conclusion, existing RAMs to evaluate the need of thromboprophylaxis in acutely ill medical patients are difficult to compare and none fulfills the criteria of an ideal RAM. Nevertheless, the adequacy of thromboprophylaxis may be improved by implementing one of the validated RAMs.

Background The association between cancer and venous thromboembolism (VTE) in producing adverse clinical outcomes requires further investigation. Methods In the Swiss Venous ThromboEmbolism Registry (SWIVTER), we compared adverse clinical outcomes between 493 patients with cancer-associated VTE and 1,569 VTE patients without cancer, and identified independent predictors of 90-day mortality. Results Among cancer patients, 351 (71%) had active disease at the time of VTE diagnosis and 232 (47%) had metastatic disease. Cancer patients more frequently had asymptomatic VTE (13 vs. 4%; p < 0.001), iliofemoral deep vein thrombosis (42 vs. 32%; p = 0.017), and upper extremity deep vein thrombosis (16 vs. 7%; p < 0.001). Cancer was associated with an increased risk of cumulative 90-day mortality (13.0 vs. 2.2%; hazard ratio [HR], 6.27; 95% confidence interval [CI], 4.13-9.50; p < 0.001), recurrent VTE (4.7 vs. 2.3%; HR, 2.05; 95% CI, 1.21-3.45; p = 0.007), and bleeding requiring medical attention (5.7 vs. 3.3%; HR, 1.80; 95% CI, 1.13-2.86; p = 0.013). Among cancer patients, the strongest factor associated with mortality was metastatic disease (HR, 4.86; 95% CI, 2.68-8.81; p < 0.001), whereas it was pulmonary embolism among noncancer patients (HR, 4.96; 95% CI, 1.50-16.45; p = 0.009). Symptomatic as compared with asymptomatic VTE predicted neither mortality (12.6 vs. 15.9%; HR, 0.76; 95% CI, 0.39-1.49; p = 0.42) nor recurrent VTE (4.7 vs. 4.8%; HR, 0.98; 95% CI, 0.29-3.31; p = 0.98) in cancer patients. Conclusion In SWIVTER, early mortality of cancer-associated VTE was mainly driven by the extent of cancer disease and not by VTE symptoms or severity., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

We investigated three-month clinical outcomes in patients with venous thromboembolism (VTE) treated with rivaroxaban or conventional anticoagulation in routine clinical practice. Between November 2012 and February 2015, 2,062 consecutive patients with VTE from 11 acute care hospitals in Switzerland were enrolled in the SWIss Venous ThromboEmbolism Registry (SWIVTER). Overall, 417 (20 %) patients were treated with rivaroxaban. In comparison to 1,645 patients on conventional anticoagulation, patients on rivaroxaban were younger (56 ± 18 vs. 65 ± 17 years; p<0.001), less often had pulmonary embolism (38 % vs 66 %; p<0.001), hypertension (26 % vs 41 %; p<0.001), cancer (10 % vs 28 %; p<0.001), congestive heart failure (10 % vs 17 %; p=0.001), diabetes (8 % vs 15 %; p<0.001), chronic lung disease (7 % vs 13 %; p=0.001), renal insufficiency (7 % vs 13 %; p=0.001), recent surgery (7 % vs 14 %; p<0.001), and acute coronary syndrome (1 % vs 4 %; p=0.009). VTE reperfusion therapy was more frequently used (28 % vs 9 %; p<0.001) and indefinite-duration anticoagulation treatment less often planned (26 % vs 39 %; p<0.001), respectively. In the propensity score-adjusted population, the risk of recurrent VTE was similar in patients on rivaroxaban vs conventional anticoagulation (1.2 % vs 2.1 %, hazard ratio [HR] 0.55, 95 % confidence interval [CI] 0.18-1.65; p=0.29); the risk of major bleeding was also similar, respectively (0.5 % vs 0.5 %, HR 1.00, 95 %CI 0.14-7.07; p=1.00). Conventional anticoagulation is still frequently used for the treatment of VTE, particularly in the elderly and those with comorbidities. Early clinical outcomes were comparable between propensity score-adjusted patient populations on rivaroxaban and conventional anticoagulation.

Background: Many patients with atrial fibrillation (AF) do not receive oral anticoagulants (OAC) for the prevention of stroke and systemic embolism. We aimed to improve the prescription of (OAC) among hospitalized patients with AF., Methods and Results: We developed a computer-based electronic alert system for identifying hospitalized OAC-naïve patients with AF. The alert system contained a CHA2DS2-VASc score calculation tool and provided recommendations for OAC prescription. The alert system was tested in a 1:1 randomized controlled trial at the University Hospital Bern: Patients with suspected AF without an active prescription order were allocated to an alert group in which an alert was issued in the electronic patient chart and order entry system or to a control group in which no alert was issued. The primary end point was the rate of adequate OAC prescription at hospital discharge, defined as prescription in OAC-naïve men and women with CHA2DS2-VASc score ≥1 and ≥2, respectively. Overall, 889 OAC-naïve patients (455 from the alert group and 434 from the control group) were eligible for analysis. Although the CHA2DS2-VASc score module was used in only 48 (10.5%) patients from the alert group, 100 (22.0%) patients from the alert group versus 69 (15.9%) from the control group received adequate OAC prescription (relative risk 1.38; P=0.021). OAC or antiplatelet therapy was prescribed in 325 (71.4%) patients from the alert group versus 271 (62.4%) from the control group (P=0.004)., Conclusions: Versus standard care, the alert system modestly improved OAC prescription among consecutive hospitalized AF patients., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02455102., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Both, underuse and overuse of thromboprophylaxis in hospitalised medical patients is common. We aimed to explore clinical factors associated with the use of pharmacological or mechanical thromboprophylaxis in acutely ill medical patients at high (Geneva Risk Score ≥ 3 points) vs low (Geneva Risk Score < 3 points) risk of venous thromboembolism. Overall, 1,478 hospitalised medical patients from eight large Swiss hospitals were enrolled in the prospective Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE) cohort study. The study is registered on ClinicalTrials.gov, number NCT01277536. Thromboprophylaxis increased stepwise with increasing Geneva Risk Score (p< 0.001). Among the 962 high-risk patients, 366 (38 %) received no thromboprophylaxis; cancer-associated thrombocytopenia (OR 4.78, 95 % CI 2.75-8.31, p< 0.001), active bleeding on admission (OR 2.88, 95 % CI 1.69-4.92, p< 0.001), and thrombocytopenia without cancer (OR 2.54, 95 % CI 1.31-4.95, p=0.006) were independently associated with the absence of prophylaxis. The use of thromboprophylaxis declined with increasing severity of thrombocytopenia (p=0.001). Among the 516 low-risk patients, 245 (48 %) received thromboprophylaxis; none of the investigated clinical factors predicted its use. In conclusion, in acutely ill medical patients, bleeding and thrombocytopenia were the most important factors for the absence of thromboprophylaxis among high-risk patients. The use of thromboprophylaxis among low-risk patients was inconsistent, without clearly identifiable predictors, and should be addressed in further research.

Principles: We aimed to evaluate the efficacy of, and treatment satisfaction with, insulin glargine administered with SoloSTAR® or ClikSTAR® pens in patients with type 2 diabetes mellitus managed by primary care physicians in Switzerland., Methods: A total of 327 patients with inadequately controlled type 2 diabetes were enrolled by 72 physicians in this prospective observational study, which aimed to evaluate the efficacy of a 6-month course of insulin glargine therapy measured as development of glycaemic control (glycosylated haemoglobin [HbA1c] and fasting plasma glucose [FPG]) and weight change. We also assessed preference for reusable or disposable pens, and treatment satisfaction., Results: After 6 months, the mean daily dose of insulin glargine was 27.7±14.3 U, and dose titration was completed in 228 (72.4%) patients. Mean HbA1c decreased from 8.9%±1.6% (n=327) to 7.3%±1.0% (n=315) (p<0.0001), and 138 (43.8%) patients achieved an HbA1c≤7.0%. Mean FPG decreased from 10.9±4.5 to 7.3±1.8 mmol/l (p<0.0001). Mean body weight did not change (85.4±17.2 kg vs 85.0±16.5 kg; p=0.11). Patients' preference was in favour of the disposable SoloStar® pen (80%), as compared with the reusable ClickStar® pen (20%). Overall, 92.6% of physicians and 96.3% of patients were satisfied or very satisfied with the insulin glargine therapy., Conclusions: In patients with type 2 diabetes insulin glargine administered by SoloSTAR® or ClikSTAR® pens, education on insulin injection and on self-management of diabetes was associated with clinically meaningful improvements in HbA1c and FPG without a mean collective weight gain. The vast majority of both patients and primary care physicians were satisfied with the treatment intensification.

Background: For patients with acute iliofemoral deep vein thrombosis, it remains unclear whether the addition of intravascular high-frequency, low-power ultrasound energy facilitates the resolution of thrombosis during catheter-directed thrombolysis., Methods and Results: In a controlled clinical trial, 48 patients (mean age 50 ± 21 years, 52% women) with acute iliofemoral deep vein thrombosis were randomized to receive ultrasound-assisted catheter-directed thrombolysis (N = 24) or conventional catheter-directed thrombolysis (N = 24). Thrombolysis regimen (20 mg r-tPA over 15 hours) was identical in all patients. The primary efficacy end point was the percentage of thrombus load reduction from baseline to 15 hours according to the length-adjusted thrombus score, obtained from standardized venograms and evaluated by a core laboratory blinded to group assignment. The percentage of thrombus load reduction was 55% ± 27% in the ultrasound-assisted catheter-directed thrombolysis group and 54% ± 27% in the conventional catheter-directed thrombolysis group (P = 0.91). Adjunctive angioplasty and stenting was performed in 19 (80%) patients and in 20 (83%) patients, respectively (P > 0.99). Treatment-related complications occurred in 3 (12%) and 2 (8%) patients, respectively (P > 0.99). At 3-month follow-up, primary venous patency was 100% in the ultrasound-assisted catheter-directed thrombolysis group and 96% in the conventional catheter-directed thrombolysis group (P = 0.33), and there was no difference in the severity of the post-thrombotic syndrome (mean Villalta score: 3.0 ± 3.9 [range 0-15] versus 1.9 ± 1.9 [range 0-7]; P=0.21), respectively., Conclusions: In this randomized controlled clinical trial of patients with acute iliofemoral deep vein thrombosis treated with a fixed-dose catheter thrombolysis regimen, the addition of intravascular ultrasound did not facilitate thrombus resolution., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT01482273., (© 2015 American Heart Association, Inc.)

Patients with ilio-femoral deep-vein thrombosis (DVT) are at high risk of developing the post-thrombotic syndrome (PTS). In comparison to anticoagulation therapy alone, extended venography-guided catheter-directed thrombolysis without routine stenting of venous stenosis in patients with ilio-femoral DVT is associated with an increased risk of bleeding and a moderate reduction of PTS. We performed a prospective single-centre study to investigate safety, patency and incidence of PTS in patients with acute ilio-femoral DVT treated with fixed-dose ultrasound-assisted catheter-directed thrombolysis (USAT; 20 mg rt-PA during 15 hours) followed by routing stenting of venous stenosis, defined as residual luminal narrowing >50%, absent antegrade flow, or presence of collateral flow at the site of suspected stenosis. A total of 87 patients (age 46 ± 21 years, 60% women) were included. At 15 hours, thrombolysis success ≥50% was achieved in 67 (77%) patients. Venous stenting (mean 1.9 ± 1.3 stents) was performed in 70 (80%) patients, with the common iliac vein as the most frequent stenting site (83%). One major (1%; 95% CI, 0-6%) and 6 minor bleedings (7%; 95%CI, 3-14%) occurred. Primary and secondary patency rates at 1 year were 87% (95% CI, 74-94%) and 96% (95% CI, 88-99%), respectively. At three months, 88% (95% CI, 78-94%) of patients were free from PTS according to the Villalta scale, with a similar rate at one year (94%, 95% CI, 81-99%). In conclusion, a fixed-dose USAT regimen followed by routine stenting of underlying venous stenosis in patients with ilio-femoral DVT was associated with a low bleeding rate, high patency rates, and a low incidence of PTS.

There is a need to validate risk assessment tools for hospitalised medical patients at risk of venous thromboembolism (VTE). We investigated whether a predefined cut-off of the Geneva Risk Score, as compared to the Padua Prediction Score, accurately distinguishes low-risk from high-risk patients regardless of the use of thromboprophylaxis. In the multicentre, prospective Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE) cohort study, 1,478 hospitalised medical patients were enrolled of whom 637 (43%) did not receive thromboprophylaxis. The primary endpoint was symptomatic VTE or VTE-related death at 90 days. The study is registered at ClinicalTrials.gov, number NCT01277536. According to the Geneva Risk Score, the cumulative rate of the primary endpoint was 3.2% (95% confidence interval [CI] 2.2-4.6%) in 962 high-risk vs 0.6% (95% CI 0.2-1.9%) in 516 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.5% vs 0.8% (p=0.029), respectively. In comparison, the Padua Prediction Score yielded a cumulative rate of the primary endpoint of 3.5% (95% CI 2.3-5.3%) in 714 high-risk vs 1.1% (95% CI 0.6-2.3%) in 764 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.2% vs 1.5% (p=0.130), respectively. Negative likelihood ratio was 0.28 (95% CI 0.10-0.83) for the Geneva Risk Score and 0.51 (95% CI 0.28-0.93) for the Padua Prediction Score. In conclusion, among hospitalised medical patients, the Geneva Risk Score predicted VTE and VTE-related mortality and compared favourably with the Padua Prediction Score, particularly for its accuracy to identify low-risk patients who do not require thromboprophylaxis.

Hypertension in the elderly is a major risk factor for cardiovascular disease. We aimed to analyze determinants of blood pressure (BP) control across different age groups. Population of a large global survey on hypertension treatment and control including 18927 patients was analyzed. A logistic regression analysis was conducted to estimate BP control rates and the prevalence of antihypertensive drug usage according to age. Systolic BP control decreased from 29.6% (95% confidence intervals (CI) 26.0;33.5) at 18-40 years to 22.4% (20.8;24.2) at >75 years (P<0.0001), and diastolic BP control increased from 31.6% (27.9;35.6) to 57.3% (55.2;59.3), respectively (P<0.0001). BP control was worse in diabetic patients, but did not differ substantially with co-morbid conditions, except for a better control in patients with myocardial infarction (MI) (P<0.05). The use of ≥ 3 antihypertensive drugs increased with age from 16.1 to 37.8% (P<0.0001) due to a more frequent use of loop diuretics (P<0.0001), thiazides (P<0.0001), angiotensin-converting enzyme (ACE) inhibitors (P<0.0001) and calcium channel blockers (P<0.0001). About one third of patients received non-guideline-recommended drug-drug combinations. BP control is largely unsuccessful with increasing age. Owing to frequent inadequacies in the combination of antihypertensive drugs, future guidelines and educational programs should devote increased attention to the choice of optimal drug-drug combinations in the elderly.