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Rationale: National and international societies have published guidelines regarding glycaemic control in type-2 diabetes mellitus. Clinical studies have shown that glycaemic control of type2 diabetes mellitus can be improved using simple algorithms for titration of insulin Glargine (Lantus®). It is unclear, to what degree published guidelines are adopted in daily practice in Switzerland, Methods: We performed a postmarketing study on the adoption of published guidelines regarding glycaemic control and the use of algorithms for titration of insulin Glargine doses by 77 general practitioners in Switzerland. Data collection was done prospectively over 6 months from September 2005 to September 2007. Results: A total of 317 patients were included with a mean age of 63 ± 11 years, 137 (43%) were female and 298 (94%) had type-2 diabetes. Average diabetes duration was 8 ± 6 years. The initial average HbA1C and fasting plasma glucose were 8.9 ± 1.6% and 10.1 ± 3.2 mmol/l respectively. This, despite treatment with at least one oral hypoglycaemic agent (83% of patients) and/or insulin (47% of patients). As target the treating physicians chose an HbA1C ≤7% for 284 patients (90%) and a fasting plasma glucose ≤7 mmol/l for 245 patients (77%); thresholds that correspond to the guidelines of the Swiss Society of Endocrinology and Diabetes (SSED). The algorithm developed Riddle et al. was used by 33% of treating physicians; whereas 17% of physicians used a schedule proposed by the American Diabetes Association (ADA) and by the European Association for the Study of Diabetes (EASD) that is generally adapted by the patients themselves. During the 6-month treatment with insulin Glargine (Lantus®) 196 patients (62%) achieved the SSED guidelines for glycaemic control. On average HbA1C was reduced by 2.1% (8.9 vs. 6.8%) and fasting plasma glucose by 3 mmol/l (10.1 vs. 7.1 mmol/l). On average insulin dose was increased by 14 IU (from 16 to 30 IU). Overall 91% of patients were satisfied with the way insulin doses were adapted. In 64% general wellbeing improved during the treatment period and in 27% it was unchanged. Conclusion: In daily practise in Switzerland the recommendations of the SSED are implemented to a high degree. Using insulin Glargine (Lantus®) recommended goals of glycaemia can be rapidly and adequately achieved and patient satisfaction can be improved. [ABSTRACT FROM AUTHOR]

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.

Background: Elevated Lp(a) (lipoprotein[a]) is a risk marker for atherosclerotic disease, but the underlying mechanisms remain elusive. We examined the association of Lp(a) with changes in coronary atherosclerosis following intensive lipid-lowering therapy., Methods: In the PACMAN-AMI trial (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction), 300 patients with acute myocardial infarction were randomized to receive biweekly alirocumab 150 mg or placebo in addition to high-intensity statins. Patients underwent serial 2-vessel intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy in the non-infarct-related arteries at baseline and after 52 weeks. The main end points were percent atheroma volume by intravascular ultrasound, minimum fibrous cap thickness by optical coherence tomography, and maximum lipid core burden index within 4 mm (maxLCBI 4mm ) by near-infrared spectroscopy., Results: A total of 265 patients had serial intravascular ultrasound data (mean age, 58±9 years; 16% women). Alirocumab resulted in greater reductions in percent atheroma volume and maxLCBI 4mm , as well as a greater increase in minimum fibrous cap thickness, compared with placebo. In the alirocumab group, the reduction in maxLCBI 4mm was smaller in patients with higher baseline Lp(a), defined by the highest quartile (Q4, ≥98 nmol/L; n=30), than in those with lower baseline Lp(a) (Q1-Q3, <98 nmol/L; n=99; -40.2 [-91.1 to 10.7] versus -91.4 [-113.9 to -68.9], respectively; P =0.01 after adjustment for clinically relevant baseline variables), and was comparable to the maxLBI 4mm reduction in the placebo group (-37.60 [-57.40 to -17.80]; n=134). These findings were consistent when higher baseline Lp(a) was defined by cut-off values of ≥75 versus <75 nmol/L (n=35 versus 94, respectively, in the alirocumab group) and ≥125 versus <125 nmol/L (n=23 versus 106, respectively). Changes in percent atheroma volume and minimum fibrous cap thickness did not differ in relation to baseline Lp(a)., Conclusions: In patients with acute myocardial infarction, elevated Lp(a) at baseline is associated with attenuation of plaque lipid regression despite intensive treatment with alirocumab plus high-intensity statin. This finding may explain the residual cardiovascular risk associated with high Lp(a) despite optimal control of lipid levels., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03067844., Competing Interests: Dr Koskinas has received speaker fees from Amgen, Sanofi, and Daiichi Sankyo. Dr Kakizaki has received speaker fees from Abbott Medical, Boston Scientific, Philips, OrbusNeich Medical, Terumo, Eli Lilly, Mochida Pharmaceutical, Novartis, Kowa, Takeda Pharmaceuticals, Ono Pharmaceutical, Boehringer Ingelheim, Daiichi Sankyo, Mitsubishi Tanabe Pharma, AstraZeneca, and consulting fees from Infraredx. Dr van Geuns reported grants and personal fees from Boston Scientific, Abbott Vascular, Astra Zeneca, Amgen, and grants from InfraRedx. Dr Praz has received travel expenses from Abbott Vascular, Edwards Lifesciences, Polares Medical, Medira, and Siemens Healthineers. Dr Spirk reports personal fees from Sanofi-Aventis (Switzerland), outside the submitted work. Dr Lanz has received speaker fees to the institution from Abbott and Edwards Lifesciences. Drs Heg and Losdat are 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 the design, conduct, or analysis of clinical studies funded by not-for-profit and for-profit organizations. Dr Windecker has received 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 & Dohme, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Swiss, Pfizer, Polares, Regeneron, Sanofi, Servier, Sinomed, Terumo, Vifor, and V-Wave. He serves as an unpaid advisory board member and 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 from pharmaceutical companies or device manufacturers. Dr Engstrøm has received speaker fees from Abbott Vascular. Dr Lang has received consultancy fees and research grants from AOP Health, Johnson & Johnson, MSD, United Therapeutics, Sanofi, Medtronic, Novo Nordisk, Neutrolis, and Pulnovo. Dr Räber has received grants from Sanofi, Regeneron, and Infraredx to the institution, speaker fees from Sanofi, and grants from Abbott, HeartFlow, Boston Scientific, and Biotronik to the institution, as well as grants from Abbott, Amgen, AstraZeneca, Occlutech, Sanofi, Canon, and Medtronic for speaker and consultation fees outside the submitted work. The other authors report no conflicts.

Background: The global impact of the COVID-19 pandemic has prompted the search for strategies to improve outcomes in affected individuals, including those initially managed in outpatient settings. Thromboembolic events have been reported as a concerning complication., Objectives: The aim of this study was to evaluate efficacy and safety of primary thromboprophylaxis in outpatients with COVID-19. The study protocol was registered in PROSPERO (CRD42022362776)., Methods: The study adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and conducted a comprehensive search of PubMed/MEDLINE, ClinicalTrials.gov, and OVID/Embase and CENTRAL from Cochrane for studies up to December 11, 2023, without language restrictions. Randomized controlled trials comparing prophylactic-dose anticoagulation with placebo or standard of care in symptomatic outpatients with COVID-19 were included in this analysis. The primary outcome was the composite of all-cause hospitalization and death within 30 days. Secondary outcomes included venous thromboembolism, the composite of venous thromboembolism and major arterial cardiovascular events, and the individual components of the primary outcome., Results: Seven randomized controlled trials and 3758 COVID-19 outpatients were included. When compared with placebo or standard of care, thromboprophylaxis was associated with similar rates of all-cause hospitalization or mortality (relative risk, 1.00; 95% CI, 0.77-1.31) and lower rates of venous thromboembolism (relative risk, 0.28; 95% CI, 0.08-0.94), corresponding to a 0.6% absolute risk reduction and number needed to treat of 174., Conclusion: Thromboprophylaxis in symptomatic COVID-19 outpatients led to reduction in venous thromboembolism risk, with no impact on hospitalization or death. However, the overall low absolute risk reduction may not support its routine use., (© 2024 The Author(s).)

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.