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Background: Dual antiplatelet therapy (DAPT) reduces ischemic events but increases bleeding risk, especially in patients with high bleeding risk (HBR). This study aimed to compare outcomes of abbreviated versus standard DAPT strategies in patients with HBR with acute coronary syndrome undergoing percutaneous coronary intervention., Methods and Results: Patients from the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-Based Bare in Heart Disease Evaluated According to Recommended Therapies) registry with at least 1 HBR criterion who underwent percutaneous coronary intervention for acute coronary syndrome were identified and included. Patients were divided into 2 groups based on their planned DAPT time at discharge: 12-month DAPT or an abbreviated DAPT strategy and matched according to their prescribed P2Y12 inhibitor at discharge. The primary outcome assessed was time to net adverse clinical events at 1 year, which encompassed cardiac death, myocardial infarction, ischemic stroke, or clinically significant bleeding. Time to major adverse cardiovascular events and the individual components of net adverse clinical events were considered secondary end points. A total of 4583 patients were included in each group. The most frequently met HBR criteria was age older than 75 years (65.6%) and Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy score ≥25 (44.6%) in the standard DAPT group and oral anticoagulant therapy (79.6%) and age 75 years and older (55.2%) in the abbreviated DAPT group. There was no statistically significant difference in net adverse clinical events (12.9% versus 13.1%; hazard ratio [HR], 0.99 [95% CI, 0.88-1.11], P =0.83), major adverse cardiovascular events (8.6% versus 7.9%; HR, 1.08 [95% CI, 0.94-1.25]), or their components between groups. The results were consistent among all of the investigated subgroups., Conclusions: In patients with HBR undergoing percutaneous coronary intervention due to acute coronary syndrome, abbreviated DAPT was associated with comparable rates of net adverse clinical events and major adverse cardiovascular events to a DAPT duration of 12 months.

Aims: The role of coronary calcification on clinical outcomes among different revascularization strategies in patients presenting with acute coronary syndromes (ACSs) has been rarely investigated. The aim of this investigation is to evaluate the role of coronary calcification, detected by coronary angiography, in the whole spectrum of patients presenting with acute ACS., Methods and Results: The present study was a post hoc analysis of the MATRIX programme. The primary endpoint was major adverse cardiovascular events (MACE), defined as the composite of all-cause mortality, myocardial infarction (MI), or stroke up to 365 days. Among the 8404 patients randomized in the MATRIX trial, data about coronary calcification were available in 7446 (88.6%) and therefore were included in this post hoc analysis. Overall, 875 patients (11.7%) presented with severe coronary calcification, while 6571 patients (88.3%) did not present severe coronary calcification on coronary angiography. Fewer patients with severe coronary calcification underwent percutaneous coronary intervention whereas coronary artery bypass grafting or medical therapy-only was more frequent compared with patients without severe calcification. At 1-year follow-up, MACE occurred in 237 (27.1%) patients with severe calcified coronary lesions and 985 (15%) patients without severe coronary calcified lesions [hazard ratio (HR) 1.91; 95% confidence interval (CI) 1.66-2.20, P < 0.001]. All-cause mortality was 8.6% in patients presenting with and 3.7% in those without severe coronary calcification (HR 2.38, 1.84-3.09, P < 0.001). Patients with severe coronary calcification incurred higher rate of MI (20.1% vs. 11.5%, HR 1.81; 95% CI 1.53-2.1, P < 0.001) and similar rate of stroke (0.8% vs. 0.6%, HR 1.35; 95% CI 0.61-3.02, P = 0.46)., Conclusion: Patients with ACS and severe coronary calcification, as compared to those without, are associated with worse clinical outcomes irrespective of the management strategy., Competing Interests: Conflict of interest: J.S.S. has received minor speaking honoraria from Terumo, Cordis, Biotronik, and Medtronic. H.M.G.-G. reports the following institutional grant support: Biotronik, Boston Scientific, Medtronic, Abbott, Neovasc, Shockwave, Phillips, and Corflow. G.A. reports minor speaking honoraria from Chiesi, Daiichi Sankyo, Boeringer Ingelheim, Bayer, Pfizer, and Biosensors. D.H. has participated on data safety monitoring board or advisory board of switch. S.L. has received consulting fees from AstraZeneca, Bayer, BMS/Pfizer, Chiesi, Daiichi-Sankyo, Icon, and Novonordisk. M.S. has received consulting fees from Abbott Vascular and iVascular. A.v.H. reports unrestricted grants from Medtronic, Abbott Vascular, and Boehringer Ingelheim and consulting fees from Celecor Therapeutics. P.V. reports consulting fees from Daiichi Sankyo, CSL Behring, Pfizer/Bristol Meyers Squibb alliance, Bayer AG, and Novartis; minor speaking honoraria from Daicchi Sankyo and Pfizer/Bristol Meyers Squibb alliance. M.V. reports consulting fees from Abbott, Alvimedica, Bayer Healthcare, Biotronik, Boston Scientific Corporation, Chiesi Farmaceutici, CoreFlow, Daiichi Sankyo, Idorsia, Medtronic, Novartis Pharma, PHASEBIO, Terumo, University of Basel, Vesalio, and Vifor Pharma. The rest of authors have no disclosures to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Patients with diabetes have increased rates of major adverse cardiac events (MACEs). We hypothesized that this is explained by diabetes-associated differences in coronary plaque morphology and lipid content., Methods: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), 898 patients with acute myocardial infarction with or without ST-segment elevation underwent 3-vessel quantitative coronary angiography and coregistered near-infrared spectroscopy and intravascular ultrasound imaging after successful percutaneous coronary intervention. Subsequent MACEs were adjudicated to either treated culprit lesions or untreated nonculprit lesions. This substudy stratified patients by diabetes status and assessed baseline culprit and nonculprit prevalence of high-risk plaque characteristics defined as maximum plaque burden ≥70% and maximum lipid core burden index ≥324.7. Separate covariate-adjusted multivariable models were performed to identify whether diabetes was associated with nonculprit lesion-related MACEs and high-risk plaque characteristics., Results: Diabetes was present in 109 of 898 patients (12.1%). During a median 3.7-year follow-up, MACEs occurred more frequently in patients with versus without diabetes (20.1% versus 13.5% [odds ratio (OR), 1.94 (95% CI, 1.14-3.30)]), primarily attributable to increased risk of myocardial infarction related to culprit lesion restenosis (4.3% versus 1.1% [OR, 3.78 (95% CI, 1.12-12.77)]) and nonculprit lesion-related spontaneous myocardial infarction (9.3% versus 3.8% [OR, 2.74 (95% CI, 1.25-6.04)]). However, baseline prevalence of high-risk plaque characteristics was similar for patients with versus without diabetes concerning culprit (maximum plaque burden ≥70%: 90% versus 93%, P =0.34; maximum lipid core burden index ≥324.7: 66% versus 70%, P =0.49) and nonculprit lesions (maximum plaque burden ≥70%: 23% versus 22%, P =0.37; maximum lipid core burden index ≥324.7: 26% versus 24%, P =0.47). In multivariable models, diabetes was associated with MACEs in nonculprit lesions (adjusted OR, 2.47 [95% CI, 1.21-5.04]) but not with prevalence of high-risk plaque characteristics (adjusted OR, 1.21 [95% CI, 0.86-1.69])., Conclusions: Among patients with recent myocardial infarction, both treated and untreated lesions contributed to the diabetes-associated ≈2-fold increased MACE rate during the 3.7-year follow-up. Diabetes-related plaque characteristics that might underlie this increased risk were not identified by multimodality imaging., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02171065.

Background: The occurrence of acute kidney injury (AKI) among patients with acute coronary syndrome (ACS) undergoing invasive management is associated with worse outcomes. However, the prognostic implications of transient or in-hospital persistent AKI may differ., Objectives: The aim of this study was to evaluate the prognostic implications of transient or in-hospital persistent AKI in patients with ACS., Methods: In the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial, 203 subjects were excluded because of incomplete information or end-stage renal disease, with a study population of 8,201 patients. Transient and persistent AKI were defined as renal dysfunction no longer or still fulfilling the AKI criteria (>0.5 mg/dL or a relative >25% increase in creatinine) at discharge, respectively. Thirty-day coprimary outcomes were the out-of-hospital composite of death, myocardial infarction, or stroke (major adverse cardiovascular events [MACE]) and net adverse cardiovascular events (NACE), defined as the composite of MACE or Bleeding Academic Research Consortium type 3 or 5 bleeding., Results: Persistent and transient AKI occurred in 750 (9.1%) and 587 (7.2%) subjects, respectively. After multivariable adjustment, compared with patients without AKI, the risk for 30-day coprimary outcomes was higher in patients with persistent AKI (MACE: adjusted HR: 2.32; 95% CI: 1.48-3.64; P < 0.001; NACE: adjusted HR: 2.29; 95% CI: 1.48-3.52; P < 0.001), driven mainly by all-cause mortality (adjusted HR: 3.43; 95% CI: 2.03-5.82; P < 0.001), whereas transient AKI was not associated with higher rates of MACE or NACE. Results remained consistent when implementing the KDIGO (Kidney Disease Improving Global Outcomes) criteria., Conclusions: Among patients with ACS undergoing invasive management, in-hospital persistent but not transient AKI was associated with higher risk for 30-day MACE and NACE. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox [MATRIX]; NCT01433627)., Competing Interests: Funding Support and Author Disclosures The trial was sponsored by Società Italiana di Cardiologia Invasiva (a nonprofit organization), which received grant support from The Medicines Company and Terumo. This substudy did not receive any direct or indirect funding. Prof Leonardi has received grants and personal fees from AstraZeneca; and has received personal fees from Daiichi Sankyo, Bayer, Pfizer/Bristol Myers Squibb, ICON, Chiesi, and Novo Nordisk (all outside the submitted work). Prof Vranckx has received personal fees from Bayer, Daiichi Sankyo, and CLS Behring (all outside the submitted work). Dr Tebaldi has received research grants from GADA and Abbott Vascular; and has received personal fees from Abbott (all outside the submitted work). Prof Andò has received personal fees and nonfinancial support from Daiichi Sankyo, Boeringer Ingelheim, and Amgen; and has received personal fees from AstraZeneca, Chiesi, and Biosensors (all outside the submitted work). Dr Brugaletta has received a research grant to the institution from AstraZeneca; has received personal fees from Abbott Vascular (outside the submitted work); and has served as an advisory board member for Boston Scientific, iVascular, and Teleflex. Dr Adamo has received speaker fees from Abbott Vascular and Medtronic (all outside the submitted work). Prof Windecker has received research and educational grants to the institution from Abbott, Amgen, AstraZeneca, Bristol Myers Squibb, Bayer, Biotronik, Boston Scientific, Cardinal Health, Cardiovalve, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, Infraredx, Johnson & Johnson, Medicure, Medtronic, Novartis, Polares, OrPha Suisse, Pfizer, Regeneron, Sanofi, Sinomed, Terumo, and V-Wave; has served as an unpaid advisory board member and/or unpaid member of the steering or executive groups of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Sinomed, Terumo, V-Wave, and Xeltis (but has not received personal payments from pharmaceutical companies or device manufacturers); and is a member of the steering or executive committee groups of several investigator-initiated trials that receive funding from industry without impact on his personal remuneration. Prof Valgimigli has received grants and personal fees from Abbott, Terumo, and AstraZeneca; has received personal fees from Chiesi, Bayer, Daiichi Sankyo, Amgen, Alvimedica, Biosensors, and Idorsia; and has received grants from Medicure (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: European treatment guidelines recommend prasugrel over ticagrelor for treating patients with non-ST-elevation acute coronary syndrome (ACS), prompting several Swedish administrative regions to transition from ticagrelor to prasugrel as the preferred treatment for patients with ACS. We aim to systematically evaluate this transition to determine the relative efficacy of prasugrel versus ticagrelor in a real-world cohort of patients with ACS., Study Design and Objectives: The SWITCH SWEDEHEART trial is a prospective, multicenter, open-label, cross-sectional, stepped-wedge cluster-randomized clinical trial, in which administrative regions in Sweden will constitute the clusters. At the start of the study, all clusters will use ticagrelor as the P2Y12 inhibitor drug of choice for ACS. The order in which the clusters will implement the transition from ticagrelor to prasugrel will be randomly assigned. Every 9 months, 1 cluster will switch from ticagrelor to prasugrel as the P2Y12 inhibitor of choice for patients with ACS. The primary endpoint is the composite 1-year rate of the death, stroke, or myocardial infarction., Conclusions: The SWITCH SWEDEHEART study will provide an extensive randomized comparison between ticagrelor and prasugrel. Novel therapies are frequently costly and supported by evidence from few or small studies, and systematic evaluation after the introduction is rare. This study will establish an important standard for introducing and evaluating the effects of health care changes within our societies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Instantaneous wave-free ratio (iFR) is a coronary physiology index used to assess the severity of coronary artery stenosis to guide revascularization. iFR has previously demonstrated noninferior short-term outcome compared to fractional flow reserve (FFR), but data on longer-term outcome have been lacking., Objectives: The purpose of this study was to investigate the prespecified 5-year follow-up of the primary composite outcome of all-cause mortality, myocardial infarction, and unplanned revascularization of the iFR-SWEDEHEART trial comparing iFR vs FFR in patients with chronic and acute coronary syndromes., Methods: iFR-SWEDEHEART was a multicenter, controlled, open-label, registry-based randomized clinical trial using the Swedish Coronary Angiography and Angioplasty Registry for enrollment. A total of 2,037 patients were randomized to undergo revascularization guided by iFR or FFR., Results: No patients were lost to follow-up. At 5 years, the rate of the primary composite endpoint was 21.5% in the iFR group and 19.9% in the FFR group (HR: 1.09; 95% CI: 0.90-1.33). The rates of all-cause death (9.4% vs 7.9%; HR: 1.20; 95% CI: 0.89-1.62), nonfatal myocardial infarction (5.7% vs 5.8%; HR: 1.00; 95% CI: 0.70-1.44), and unplanned revascularization (11.6% vs 11.3%; HR: 1.02; 95% CI: 0.79-1.32) were also not different between the 2 groups. The outcomes were consistent across prespecified subgroups., Conclusions: In patients with chronic or acute coronary syndromes, an iFR-guided revascularization strategy was associated with no difference in the 5-year composite outcome of death, myocardial infarction, and unplanned revascularization compared with an FFR-guided revascularization strategy. (Evaluation of iFR vs FFR in Stable Angina or Acute Coronary Syndrome [iFR SWEDEHEART]; NCT02166736)., Competing Interests: Funding Support and Author Disclosures This study was funded by an unrestricted research grant from Philips Volcano to the Uppsala Clinical Research Center. Dr Götberg has received lecture fees from Boston Scientific and Volcano; has received consulting fees from Boston Scientific; and has received fees for serving on an advisory board from Medtronic. Dr Sandhall has received lecture fees from Boston Scientific and Philips Volcano; and has received consulting fees from Boston Scientific. Dr Maeng has received speaker and advisory board fees from Novo Nordisk. Dr Omerovic has received grant support from Abbott and AstraZeneca; and has received fees for serving on an advisory board from AstraZeneca. Dr Fröbert has received grant support from Sanofi-Pasteur. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In patients with chronic coronary syndrome undergoing percutaneous coronary intervention, the optimal timing of P2Y12 inhibitors' administration is uncertain. We compared pretreatment versus treatment in the catheterization laboratory (In-Cathlab) in a real-world population., Methods: In Swedish Coronary Angiography and Angioplasty Registry, all patients with chronic coronary syndrome undergoing coronary angiography and ad hoc percutaneous coronary intervention, between 2006 and 2017 were identified. Pretreatment was defined as P2Y12 inhibitor administration before coronary angiography, outside the catheterization laboratory. Outcomes were net adverse clinical events including death, myocardial infarction, stroke, or bleeding within 30 days of the index procedure and in-hospital bleeding., Results: We included 26 814 patients, 8237 in the In-Cathlab, and 18 577 in the pretreatment group. In-Cathlab treatment compared with pretreatment was associated with lower risk for net adverse clinical event (4.2 versus 5.1%, adjusted hazard ratio 0.79 [0.63-0.99]), bleeding (2.3 versus 2.6%, adjusted hazard ratio, 0.76 [0.57-1.01]). and in-hospital bleeding (1.9 versus 2.1%, adjusted odds ratio, 0.70 [0.51-0.96]). The risk for death, myocardial infarction, or stroke did not significantly differ between the groups. Among the In-Cathlab treated patients, 41% received ticagrelor or prasugrel and 59% clopidogrel. Treatment with ticagrelor or prasugrel was associated with higher risk for net adverse clinical events (5.4% versus 3.4%, adjusted hazard ratio, 1.66 [1.12-2.48]), bleeding (3.4 versus 1.6%, adjusted hazard ratio, 2.14 [1.34-3.42]), and in-hospital bleeding (2.9 versus 1.2%, adjusted odds ratio, 2.24 [1.29-3.90]) but similar risk for death, myocardial infarction, or stroke, compared with clopidogrel., Conclusions: In patients with chronic coronary syndrome undergoing coronary angiography and ad hoc percutaneous coronary intervention, pretreatment with P2Y12 inhibitors, before arrival to the catheterization laboratory, was not associated with improved clinical outcomes but was associated with increased risk for bleeding. Our data support clopidogrel administration in the catheterization laboratory as the standard of care. Graphic Abstract: A graphic abstract is available for this article.

Importance: Guidelines recommend dual antiplatelet therapy after coronary artery bypass grafting (CABG) for patients with acute coronary syndrome (ACS). However, the evidence for these recommendations is weak., Objective: To compare midterm outcomes after CABG in patients with ACS treated postoperatively with acetylsalicylic acid (ASA) and ticagrelor or with ASA monotherapy., Design, Setting, and Participants: This cohort study used merged data from several national registries of Swedish patients who were diagnosed with ACS and subsequently underwent CABG. All included patients underwent isolated CABG in Sweden between 2012 and 2017 with an ACS diagnosis less than 6 weeks before the procedure, survived 14 days after discharge from hospital, and were treated postoperatively with ASA plus ticagrelor or ASA monotherapy. A multivariable Cox regression model was used for the main analysis, and propensity score-matched models were performed as sensitivity analysis. Data were analyzed between May and September 2020., Exposures: Postoperative antiplatelet treatment, defined as filled prescriptions, with either ASA and ticagrelor or ASA only., Main Outcomes and Measures: Major adverse cardiovascular events (MACE), defined as all-cause mortality, myocardial infarction, and stroke, and major bleeding, at 12 months and at the end of follow-up., Results: A total of 6558 patients (5281 [80.5%] men; mean [SD] age at surgery, 67.6 [9.3] years) were included; 1813 (27.6%) were treated with ASA plus ticagrelor and 4745 (72.4%) were treated with ASA monotherapy. Crude MACE rate was 3.0 per 100 person years (95% CI, 2.5-3.6 per 100 person years) in the ASA plus ticagrelor group and 3.8 per 100 person years (95% CI, 3.5-4.1 per 100 person years) in the ASA group. After adjustment, there was no significant difference in MACE risk between ASA plus ticagrelor vs ASA only, neither during the first 12 months (adjusted hazard ratio [aHR], 0.84; 95% CI, 0.58-1.21; P = .34) or during total follow-up (aHR, 0.89; 95% CI, 0.71-1.11; P = .29). The use of ASA plus ticagrelor was associated with a significantly increased risk for major bleeding during the first 12 months (aHR, 1.90; 95% CI, 1.16-3.13; P = .011). Sensitivity analyses confirmed the results., Conclusions and Relevance: In patients with ACS who survived 2 weeks after CABG, no significant difference in the risk of death or ischemic events could be demonstrated between ASA plus ticagrelor and patients treated with ASA only, while the risk for major bleeding was higher in patients treated with ASA plus ticagrelor. Sufficiently powered prospective randomized trials comparing different antiplatelet therapy strategies after CABG are warranted.

Background Ticagrelor reduces ischaemic end points in acute coronary syndromes. However, outcomes of ticagrelor versus clopidogrel in real-world patients with acute coronary syndromes treated with percutaneous coronary intervention (PCI) remain unclear. We sought to examine whether treatment with ticagrelor is superior to clopidogrel in unselected patients with acute coronary syndromes treated with PCI. Methods and Results We used data from SCAAR (Swedish Coronary Angiography and Angioplasty Registry) for PCI performed in Västra Götaland County, Sweden. The database contains information about all PCI performed at 5 hospitals (∼20% of all data in SCAAR). All procedures between January 2005 and January 2015 for unstable angina/non‒ST-segment‒elevation myocardial infarction and ST-segment‒elevation myocardial infarction were included. We used instrumental variable 2-stage least squares regression to adjust for confounders. The primary combined end point was mortality or stent thrombosis at 30 days, secondary end points were mortality at 30 days and 1-year, stent thrombosis at 30 days, in-hospital bleeding, in-hospital neurologic complications and long-term mortality. A total of 15 097 patients were included in the study of which 2929 (19.4%) were treated with ticagrelor. Treatment with ticagrelor was not associated with a lower risk for the primary end point (adjusted odds ratio [aOR], 1.20; 95% CI, 0.87-1.61; P =0.250). Estimated risk of death at 30 days (aOR, 1.18; 95% CI, 0.88-1.64; P =0.287) and at 1-year (aOR, 1.28; 95% CI, 0.86-1.64; P =0.556) was not different between the groups. The risk of in-hospital bleeding was higher with ticagrelor (aOR, 2.88; 95% CI, 1.53-5.44; P =0.001). Conclusions In this observational study, treatment with ticagrelor was not superior to clopidogrel in patients with acute coronary syndromes treated with PCI.

Aims: In the Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART), bivalirudin was not superior to unfractionated heparin in patients with acute coronary syndrome undergoing invasive management. We assessed whether the access site had an impact on the primary endpoint of death, myocardial infarction or major bleeding at 180 days and whether it interacted with bivalirudin/unfractionated heparin., Methods and Results: A total of 6006 patients with acute coronary syndrome planned for percutaneous coronary intervention were randomised to either bivalirudin or unfractionated heparin. Arterial access was left to the operator discretion. Overall, 90.5% of patients underwent transradial access and 9.5% transfemoral access. Baseline risk was higher in transfemoral access. The unadjusted hazard ratio for the primary outcome was lower with transradial access (hazard ratio 0.53, 95% confidence interval 0.43-0.67, p <0.001) and remained lower after multivariable adjustment (hazard ratio 0.56, 95% confidence interval 0.52-0.84, p <0.001). Transradial access was associated with lower risk of death (hazard ratio 0.41, 95% confidence interval 0.28-0.60, p <0.001) and major bleeding (hazard ratio 0.57, 95% confidence interval 0.44-0.75, p <0.001). There was no interaction between treatment with bivalirudin and access site for the primary endpoint ( p =0.976) or major bleeding ( p =0.801)., Conclusions: Transradial access was associated with lower risk of death, myocardial infarction or major bleeding at 180 days. Bivalirudin was not associated with less bleeding, irrespective of access site.

Aims: Our aim was to assess whether bivalirudin compared with unfractionated heparin (UFH) is associated with consistent outcomes in males and females with acute coronary syndrome (ACS) undergoing invasive management., Methods and Results: In the MATRIX programme, 7,213 patients were randomised to bivalirudin or UFH. Patients in the bivalirudin group were subsequently randomly assigned to receive or not a post-PCI bivalirudin infusion. The 30-day co-primary outcomes were major adverse cardiovascular events (MACE), defined as death, myocardial infarction, or stroke, and net adverse clinical events (NACE), defined as MACE or major bleeding. The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target vessel revascularisation (TVR), definite stent thrombosis (ST), or NACE. The rate of MACE was not significantly lower with bivalirudin than with heparin in male (rate ratio [RR] 0.90, 95% confidence interval [CI]: 0.75-1.07; p=0.22) and female patients (RR 1.06, 95% CI: 0.80-1.40; p=0.67) without significant interaction (pint=0.31), nor was the rate of NACE (males: RR 0.85, 95% CI: 0.72-1.01; p=0.07; females: RR 0.98, 95% CI: 0.76-1.28; p=0.91; pint=0.38). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent TVR, definite ST, or NACE (males: RR 0.84, 95% CI: 0.66-1.07; p=0.15; females: RR 1.06, 95% CI: 0.74-1.53; p=0.74; pint=0.28)., Conclusions: In ACS patients, the rates of MACE and NACE were not significantly lower with bivalirudin than with UFH in both sexes. The rate of the composite of urgent TVR, definite ST, or NACE was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion in both sexes.

Background: The Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox (MATRIX) programme was designed to assess the comparative safety and effectiveness of radial versus femoral access and of bivalirudin versus unfractionated heparin with optional glycoprotein IIb/IIIa inhibitors in patients with the whole spectrum of acute coronary syndrome undergoing invasive management. Here we describe the prespecified final 1-year outcomes of the entire programme., Methods: MATRIX was a programme of three nested, randomised, multicentre, open-label, superiority trials in patients with acute coronary syndrome in 78 hospitals in Italy, the Netherlands, Spain, and Sweden. Patients with ST-elevation myocardial infarction were simultaneously randomly assigned (1:1) before coronary angiography to radial or femoral access and to bivalirudin, with or without post-percutaneous coronary intervention infusion or unfractionated heparin (one-step inclusion). Patients with non-ST-elevation acute coronary syndrome were randomly assigned (1:1) before coronary angiography to radial or femoral access and, only if deemed eligible to percutaneous coronary intervention after angiography (two-step inclusion), entered the antithrombin type and treatment duration programmes. Randomisation sequences were computer generated, blocked, and stratified by intended new or current use of P2Y12 inhibitor (clopidogrel vs ticagrelor or prasugrel), and acute coronary syndrome type (ST-elevation myocardial infarction, troponin-positive, or troponin-negative non-ST-elevation acute coronary syndrome). Bivalirudin was given as a bolus of 0·75 mg/kg, followed immediately by an infusion of 1·75 mg/kg per h until completion of percutaneous coronary intervention. Heparin was given at 70-100 units per kg in patients not receiving glycoprotein IIb/IIIa inhibitors, and at 50-70 units per kg in patients receiving glycoprotein IIb/IIIa inhibitors. Clinical follow-up was done at 30 days and 1 year. Co-primary outcomes for MATRIX access and MATRIX antithrombin type were major adverse cardiovascular events, defined as the composite of all-cause mortality, myocardial infarction, or stroke up to 30 days; and net adverse clinical events, defined as the composite of non-coronary artery bypass graft-related major bleeding, or major adverse cardiovascular events up to 30 days. The primary outcome for MATRIX treatment duration was the composite of urgent target vessel revascularisation, definite stent thrombosis, or net adverse clinical events up to 30 days. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01433627., Findings: Between Oct 11, 2011, and Nov 7, 2014, we randomly assigned 8404 patients to receive radial (4197 patients) or femoral (4207 patients) access. Of these 8404 patients, 7213 were included in the MATRIX antithrombin type study and were randomly assigned to bivalirudin (3610 patients) or heparin (3603 patients). Patients assigned to bivalirudin were included in the MATRIX treatment duration study, and were randomly assigned to post-procedure infusion (1799 patients) or no post-procedure infusion (1811 patients). At 1 year, major adverse cardiovascular events did not differ between patients assigned to radial access compared with those assigned to femoral access (14·2% vs 15·7%; rate ratio 0·89, 95% CI 0·80-1·00; p=0·0526), but net adverse clinical events were fewer with radial than with femoral access (15·2% vs 17·2%; 0·87, 0·78-0·97; p=0·0128). Compared with heparin, bivalirudin was not associated with fewer major adverse cardiovascular (15·8% vs 16·8%; 0·94, 0·83-1·05; p=0·28) or net adverse clinical events (17·0% vs 18·4%; 0·91, 0·81-1·02; p=0·10). The composite of urgent target vessel revascularisation, stent thrombosis, or net adverse clinical events did not differ with or without post-procedure bivalirudin infusion (17·4% vs 17·4%; 0·99, 0·84-1·16; p=0·90)., Interpretation: In patients with acute coronary syndrome, radial access was associated with lower rates of net adverse clinical events compared with femoral access, but not major adverse cardiovascular events at 1 year. Bivalirudin with or without post-procedure infusion was not associated with lower rates of major adverse cardiovascular events or net adverse clinical events. Radial access should become the default approach in acute coronary syndrome patients undergoing invasive management., Funding: Italian Society of Invasive Cardiology, The Medicines Company, Terumo, amd Canada Research Chairs Programme., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS)., Background: Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization., Methods: The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year., Results: Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p < 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04)., Conclusions: Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Contrasting evidence exists on the comparative efficacy and safety of bivalirudin and unfractionated heparin (UFH) in relation to the planned use of glycoprotein IIb/IIIa inhibitors (GPIs)., Objectives: This study assessed the efficacy and safety of bivalirudin compared with UFH with or without GPIs in patients with acute coronary syndrome (ACS) who underwent invasive management., Methods: In the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX) program, 7,213 patients were randomly assigned to receive either bivalirudin or UFH with or without GPIs at discretion of the operator. The 30-day coprimary outcomes were major adverse cardiovascular events (MACEs) (a composite of death, myocardial infarction, or stroke), and net adverse clinical events (NACEs) (a composite of MACEs or major bleeding)., Results: Among 3,603 patients assigned to receive UFH, 781 (21.7%) underwent planned treatment with GPI before coronary intervention. Bailout use of GPIs was similar between the bivalirudin and UFH groups (4.5% and 5.4%) (p = 0.11). At 30 days, the 2 coprimary endpoints of MACEs and NACEs, as well as individual endpoints of mortality, myocardial infarction, stent thrombosis or stroke did not differ among the 3 groups after adjustment. Compared with the UFH and UFH+GPI groups, bivalirudin reduced bleeding, mainly the most severe bleeds, including fatal and nonaccess site-related events, as well as transfusion rates and the need for surgical access site repair. These findings were not influenced by the administered intraprocedural dose of UFH and were confirmed at multiple sensitivity analyses, including the randomly allocated access site., Conclusions: In patients with ACS, the rates of MACEs and NACEs were not significantly lower with bivalirudin than with UFH, irrespective of planned GPI use. However, bivalirudin significantly reduced bleeding complications, mainly those not related to access site, irrespective of planned use of GPIs. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX [MATRIX]; NCT01433627)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The prognostic role of hypertension on long-term survival after percutaneous coronary intervention (PCI) is limited and inconsistent. We hypothesize that hypertension increases long-term mortality after PCI., Methods: We analyzed data from SCAAR (Swedish Coronary Angiography and Angioplasty Registry) for all consecutive patients admitted coronary care units in Sweden between January 1995 and May 2013 and who underwent PCI due to ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI)/unstable angina (UA) or stable angina pectoris. We used Cox proportional-hazards regression for statistical modelling on complete-case data as well as on imputed data sets. We used interaction test to evaluate possible effect-modulation of hypertension on risk estimates in several pre-specified subgroups: age categories, gender, diabetes, smoking and indication for PCI (STEMI, NSTEMI/UA and stable angina)., Results: During the study period, 175,892 consecutive patients underwent coronary angiography due to STEMI, NSTEMI/UA or stable angina. 78,100 (44%) of these had hypertension. Median follow-up was 5.5 years. After adjustment for differences in patient's characteristics, hypertension was associated with increased risk for mortality (HR 1.12, 95% CI 1.09-1.15, p < .001). In subgroup analysis, risk was highest in patients less than 65 years, in smokers and in patients with STEMI. The risk was lowest in patients with stable angina (p < .001 for interaction test)., Conclusion: Hypertension is associated with higher mortality in patients with STEMI, NSTEMI/UA or stable angina who are treated with PCI.

Background: The instantaneous wave-free ratio (iFR) is an index used to assess the severity of coronary-artery stenosis. The index has been tested against fractional flow reserve (FFR) in small trials, and the two measures have been found to have similar diagnostic accuracy. However, studies of clinical outcomes associated with the use of iFR are lacking. We aimed to evaluate whether iFR is noninferior to FFR with respect to the rate of subsequent major adverse cardiac events., Methods: We conducted a multicenter, randomized, controlled, open-label clinical trial using the Swedish Coronary Angiography and Angioplasty Registry for enrollment. A total of 2037 participants with stable angina or an acute coronary syndrome who had an indication for physiologically guided assessment of coronary-artery stenosis were randomly assigned to undergo revascularization guided by either iFR or FFR. The primary end point was the rate of a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization within 12 months after the procedure., Results: A primary end-point event occurred in 68 of 1012 patients (6.7%) in the iFR group and in 61 of 1007 (6.1%) in the FFR group (difference in event rates, 0.7 percentage points; 95% confidence interval [CI], -1.5 to 2.8; P=0.007 for noninferiority; hazard ratio, 1.12; 95% CI, 0.79 to 1.58; P=0.53); the upper limit of the 95% confidence interval for the difference in event rates fell within the prespecified noninferiority margin of 3.2 percentage points. The results were similar among major subgroups. The rates of myocardial infarction, target-lesion revascularization, restenosis, and stent thrombosis did not differ significantly between the two groups. A significantly higher proportion of patients in the FFR group than in the iFR group reported chest discomfort during the procedure., Conclusions: Among patients with stable angina or an acute coronary syndrome, an iFR-guided revascularization strategy was noninferior to an FFR-guided revascularization strategy with respect to the rate of major adverse cardiac events at 12 months. (Funded by Philips Volcano; iFR SWEDEHEART ClinicalTrials.gov number, NCT02166736 .).

Background: Small observational studies have indicated better outcome with intravascular ultrasound (IVUS) guidance when performing unprotected left main coronary artery (LMCA) percutaneous coronary intervention (PCI), but the overall picture remains inconclusive and warrants further investigation. We studied the impact of IVUS guidance on outcome in patients undergoing unprotected LMCA PCI in a Swedish nationwide observational study., Methods and Results: Patients who underwent unprotected LMCA PCI between 2005 and 2014 because of stable coronary artery disease or acute coronary syndrome were included from the nationwide SCAAR (Swedish Coronary Angiography and Angioplasty Registry). Of 2468 patients, IVUS guidance was used in 621 (25.2%). The IVUS group was younger (median age, 70 versus 75 years) and had fewer comorbidities but more complex lesions. IVUS was associated with larger stent diameters (median, 4 mm versus 3.5 mm). After adjusting for potential confounders, IVUS was associated with significantly lower occurrence of the primary composite end point of all-cause mortality, restenosis, or definite stent thrombosis (hazard ratio, 0.65; 95% confidence interval, 0.50-0.84) and all-cause mortality alone (hazard ratio, 0.62; 95% confidence interval, 0.47-0.82). In 340 propensity score-matched pairs, IVUS was also associated with significantly lower occurrence of the primary end point (hazard ratio, 0.54; 95% confidence interval, 0.37-0.80)., Conclusions: IVUS was associated with an independent and significant outcome benefit when performing unprotected LMCA PCI. Potential mediators of this benefit include larger and more appropriately sized stents, perhaps translating into lower risk of subsequent stent thrombosis. Although residual confounding cannot be ruled out, our findings indicate a possible hazard when performing unprotected LMCA PCI without IVUS guidance., (© 2017 American Heart Association, Inc.)

Background: Instantaneous wave-free ratio (iFR) is a new hemodynamic resting index for assessment of coronary artery stenosis severity. iFR uses high frequency sampling to calculate a gradient across a coronary lesion during a period of diastole. The index has been tested against fractional flow reserve (FFR) and found to have an overall classification agreement of 80% to 85%. Whether the level of disagreement is clinically relevant is unknown. Clinical outcome data on iFR are scarce. This study is a registry-based randomized clinical trial, which is a novel strategy using health quality registries as on-line platforms for randomization, case record forms, and follow-up., Design/methods: iFR-SWEDEHEART is a multicenter, prospective, randomized, controlled, clinical open-label clinical trial. Two thousand patients with stable angina or acute coronary syndrome and an indication for physiology-guided assessment of one or more coronary stenoses will be randomized 1:1 to either iFR- or FFR-guided intervention. The randomization will be conducted online in the Swedish web-based system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies (SWEDEHEART) registry. The trial has a non-inferiority design, with a primary combined end point of all-cause death, non-fatal myocardial infarction, and unplanned revascularization at 12 months. End points will be identified through national registries and undergo central blind adjudication to ensure data quality., Discussion: The iFR-SWEDEHEART trial is an registry-based randomized clinical trial evaluating the safety and efficacy of the diagnostic method iFR compared to FFR., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Conflicting evidence exists on the efficacy and safety of bivalirudin administered as part of percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome., Methods: We randomly assigned 7213 patients with an acute coronary syndrome for whom PCI was anticipated to receive either bivalirudin or unfractionated heparin. Patients in the bivalirudin group were subsequently randomly assigned to receive or not to receive a post-PCI bivalirudin infusion. Primary outcomes for the comparison between bivalirudin and heparin were the occurrence of major adverse cardiovascular events (a composite of death, myocardial infarction, or stroke) and net adverse clinical events (a composite of major bleeding or a major adverse cardiovascular event). The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events., Results: The rate of major adverse cardiovascular events was not significantly lower with bivalirudin than with heparin (10.3% and 10.9%, respectively; relative risk, 0.94; 95% confidence interval [CI], 0.81 to 1.09; P=0.44), nor was the rate of net adverse clinical events (11.2% and 12.4%, respectively; relative risk, 0.89; 95% CI, 0.78 to 1.03; P=0.12). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events (11.0% and 11.9%, respectively; relative risk, 0.91; 95% CI, 0.74 to 1.11; P=0.34)., Conclusions: In patients with an acute coronary syndrome, the rates of major adverse cardiovascular events and net adverse clinical events were not significantly lower with bivalirudin than with unfractionated heparin. The rate of the composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion. (Funded by the Medicines Company and Terumo Medical; MATRIX ClinicalTrials.gov number, NCT01433627.).

Aims: In the present study, we investigated the prognostic value of radial artery intima-media thickness (rIMT) in patients with suspected coronary artery disease (CAD). Carotid artery intima-media thickness is a well-known surrogate marker of atherosclerosis. Recently, using very high-resolution ultrasound, we showed rIMT can be imaged with great precision and is related to various cardiovascular risk factors., Methods and Results: We recruited a total of 416 patients (62 ± 9 years, 44% male) with suspected CAD, referred to myocardial perfusion scintigraphy (MPS). Among these patients, 133 underwent coronary angiography on clinical indication. Two-dimensional images of carotid and radial arteries were acquired bilaterally (using 8 and 55 MHz ultrasound, respectively). All patients were followed regarding major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, stroke, and coronary revascularization. A group of 20 healthy subjects (aged 61 ± 3, 50% male) were recruited for reference. During 3 years of follow-up, 77 MACE occurred. Patients with MACE exhibited significantly thicker rIMT vs. those without (0.35 ± 0.06 vs. 0.32 ± 0.07 mm, P < 0.001). Increased rIMT was associated with an increased occurrence of significant coronary artery narrowing, diagnosed by coronary angiography (P = 0.028). Patients with rIMT values above the median had a nearly three-fold increased risk for MACE (hazard ratio 2.8, 95% confidence interval 1.6-4.8). In multivariate analysis, rIMT (P = 0.011) remained a significant predictor of MACE, along with type II diabetes (P = 0.012), body mass index (P = 0.024), and MPS-verified ischaemia (P < 0.001)., Conclusion: Radial artery IMT, assessed by very high-resolution ultrasound, confers prognostic information in patients with suspected CAD., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Aims: The obesity paradox refers to the epidemiological evidence that obesity compared with normal weight is associated with counter-intuitive improved health in a variety of disease conditions. The aim of this study was to investigate the relationship between body mass index (BMI) and mortality in patients with acute coronary syndromes (ACSs)., Methods and Results: We extracted data from the Swedish Coronary Angiography and Angioplasty Registry and identified 64 436 patients who underwent coronary angiography due to ACSs. In 54 419 (84.4%) patients, a significant coronary stenosis was identified, whereas 10 017 (15.6%) patients had no significant stenosis. Patients were divided into nine different BMI categories. The patients with significant stenosis were further subdivided according to treatment received such as medical therapy, percutaneous coronary intervention (PCI), or coronary artery by-pass grafting. Mortality for the different subgroups during a maximum of 3 years was compared using Cox proportional hazards regression with the lean BMI category (21.0 to <23.5 kg/m(2)) as the reference group. Regardless of angiographic findings [significant or no significant coronary artery disease (CAD)] and treatment decision, the underweight group (BMI <18.5 kg/m(2)) had the greatest risk for mortality. Medical therapy and PCI-treated patients with modest overweight (BMI category 26.5-<28 kg/m(2)) had the lowest risk of mortality [hazard ratio (HR) 0.52; 95% CI 0.34-0.80 and HR 0.64; 95% CI 0.50-0.81, respectively]. When studying BMI as a continuous variable in patients with significant CAD, the adjusted risk for mortality decreased with increasing BMI up to ~35 kg/m(2) and then increased. In patients with significant CAD undergoing coronary artery by-pass grafting and in patients with no significant CAD, there was no difference in mortality risk in the overweight groups compared with the normal weight group., Conclusion: In this large and unselected group of patients with ACSs, the relation between BMI and mortality was U-shaped, with the nadir among overweight or obese patients and underweight and normal-weight patients having the highest risk. These data strengthen the concept of the obesity paradox substantially.

Background: Many patients who suffer from acute chest pain are transported by ambulance. It is not known how often treatment prior to hospital admission is optimal and how optimal pain-relieving treatment is defined. It is often difficult to delineate pain from anxiety., Aim: To describe various aspects of chest pain in the pre-hospital setting with the emphasis on a) treatment and b) presumed acute coronary syndrome., Methods: In the literature search, we used PubMed and the appropriate key words. We included randomised clinical trials and observational studies., Results: Four types of drug appear to be preferred: 1) narcotic analgesics, 2) nitrates, 3) beta-blockers and 4) benzodiazepines. Among narcotic analgesics, morphine has been associated with the relief of pain at the expense of side-effects. Alfentanil was reported to produce more rapid pain relief. Nitrates have been associated with the relief of pain with few side-effects. Beta-blockers have been reported to increase the relief of pain when added to morphine. The combination of beta-blockers and morphine has been reported to be as effective as beta-blockers alone in pain relief, but this combination therapy was associated with more side-effects. Experience from anxiety-relieving drugs such as benzodiazepines is limited. It is not known how these 4 drugs should be combined. The results indicate that various pain-relieving treatments might modify the disease., Conclusion: Our knowledge of the optimal treatment of chest pain and associated anxiety in the pre-hospital setting is insufficient. Recommendations from existing guidelines are limited. Large randomised clinical trials are warranted., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: The comparative efficacy and safety of prasugrel and ticagrelor in patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) remain unclear. We aimed to investigate the association of treatment with clinical outcomes.Methods: In the SWEDEHEART (Swedish Web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies) registry, all patients with MI treated with PCI and discharged on prasugrel or ticagrelor from 2010 to 2016 were included. Outcomes were 1-year major adverse cardiac and cerebrovascular events (MACCE, death, MI or stroke), individual components and bleeding. Multivariable adjustment, inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were used to adjust for confounders.Results: We included 37 990 patients, 2073 in the prasugrel group and 35 917 in the ticagrelor group. Patients in the prasugrel group were younger, more often admitted with ST elevation MI and more likely to have diabetes. Six to twelve months after discharge, 20% of patients in each group discontinued the P2Y12 receptor inhibitor they received at discharge. The risk for MACCE did not significantly differ between prasugrel-treated and ticagrelor-treated patients (adjusted HR 1.03, 95% CI 0.86 to 1.24). We found no significant difference in the adjusted risk for death, recurrent MI or stroke alone between the two treatments. There was no significant difference in the risk for bleeding with prasugrel versus ticagrelor (2.5% vs 3.2%, adjusted HR 0.92, 95% CI 0.69 to 1.22). IPTW and PSM analyses confirmed the results.Conclusion: In patients with MI treated with PCI, prasugrel and ticagrelor were associated with similar efficacy and safety during 1-year follow-up. [ABSTRACT FROM AUTHOR]

Background: Premature coronary artery disease (CAD) is a major cause of mortality and morbidity. Increased low-density lipoprotein-cholesterol (LDL-C) level is a major risk factor for CAD and thus the main target for its prevention. Familial Hypercholesterolemia (FH) is a genetic inherited disorder characterized by high LDL-C, and subsequent premature CAD development. Early drug treatment with lipid-lowering medications in FH prevents cardiovascular disease onset.   The FH prevalence in the Northern European general population is 0.3%, and it is estimated that it explains 20% of premature CAD cases in individuals with familial clustering. Despite the wide number of papers showing the prevalence of clinical FH in cardiovascular disease, the prevalence of genetic FH in individuals with premature CAD is not yet well known. Here, we examined the prevalence of genetically determined FH in individuals with premature CAD. Patients and methods: 66 patients who underwent coronary angiography with suspected premature acute coronary syndrome (age <50 years for men and <55 years for women) underwent genetic screening to identify FH-causing mutations. All patients underwent physical and clinical examinations. Information about family and personal history, drug therapy and habits were also collected. Results: We found FH-causative mutations in 3/66 (4.5%) screened individuals with premature CAD. When considering individuals with confirmed CAD after coronary angiography, the FH mutation prevalence was 6.1% (3/49). After excluding individuals with classical risk factors for CAD other than hypercholesterolemia, the FH mutation prevalence raised to 15.8% (3/19). Conclusion: In conclusion, we found that individuals with premature CAD have a more than 15-fold increased prevalence of FH mutations compared to the general population. [ABSTRACT FROM AUTHOR]

Aims Ticagrelor reduces ischaemic events and mortality in acute coronary syndrome (ACS) vs. clopidogrel. We wished to study clinical outcomes in a large real-world population post-ACS. Methods and results We performed a prospective cohort study in 45 073 ACS patients enrolled into Swedish Web system for Enhancement and Development of Evidence-based care in Heart Disease Evaluated According to Recommended Therapies who were discharged on ticagrelor (N = 11 954) or clopidogrel (N = 33 119) between 1 January 2010 and 31 December 2013. The primary outcome was a composite of all-cause death, re-admission with myocardial infarction (MI) or stroke, secondary outcomes as the individual components of the primary outcome, and re-admission with bleeding. The risk of the primary outcome with ticagrelor vs. clopidogrel was 11.7 vs. 22.3% (adjusted hazard ratio (HR) 0.85 [95% confidence interval: 0.78-0.93]), risk of death 5.8 vs. 12.9% (adjusted HR 0.83 [0.75-0.92]), and risk of MI 6.1 vs. 10.8% (adjusted HR 0.89 [0.78-1.01]) at 24 months. Re-admission with bleeding with ticagrelor vs. clopidogrel occurred in 5.5 vs. 5.2% (adjusted HR 1.20 [1.04-1.40]). In a subset of patients undergoing percutaneous coronary intervention (PCI) on ticagrelor vs. clopidogrel the PCI-related in-hospital bleeding was 3.7 vs. 2.7% (adjusted odds ratio, OR, 1.57 [1.30-1.90]). Conclusion Ticagrelor vs. clopidogrel post-ACS was associated with a lower risk of death, MI, or stroke, as well as death alone. Risk of bleeding was higher with ticagrelor. These real-world outcomes are consistent with randomized trial results. [ABSTRACT FROM AUTHOR]

Background: In this paper, we report about new insights regarding clinical course, long-term outcome, ethnic/genetic predisposition and cardio-circulatory status in the large stress-induced cardiomyopathy (SIC) cohort from Sweden. Methods and Results: We have included 115 consecutive SIC patients between January 2005 and January 2010 at SahIgrenska University Hospital in Gothenburg. Hemodynamic status and sympathetic nerve activity were evaluated and compared with those of healthy controls. Mean age was 64, and 14% were males. Thirty-day and 3-year mortality was 6 and 10%, respectively. Eleven percent had ischemic heart disease, 3% developed thromboembolic complications, 6% had cardiac arrest and 14% developed cardiogenic shock. The great majority of SIC patients (93%) were ethnic Swedes. In three families, several close relatives developed SIC. Fourteen percent developed two or more episodes of SIC. Hemodynamic evaluation has shown subnormal systemic vascular resistance, 22% lower sympathetic activity and preserved cardiac output in SIC patients: Conclusions: SIC affects both men and women of different ages and is associated with significant shortand long-term mortality. There is a strong signal for the presence of ethnic/genetic predisposition to develop SIC. Sympathetic activity and systemic vascular resistance are lower in SIC patients, suggesting that SIC is a cardio-circulatory phenomenon. [ABSTRACT FROM AUTHOR]

Stress-induced cardiomyopathy (SIC) is a novel syndrome with a substantial morbidity and mortality rate. It has become an important differential diagnosis in patients with acute chest pain. The characteristic hallmark of SIC is a development of extensive but reversible left ventricular dysfunction which may cause fulminant heart failure, cardiogenic shock and literally heart rupture leading to death. In spite of the rapidly increasing number of patients, a lot of elementary facts are unknown in regard to epidemiology, pathophysiology, prognosis and optimal treatment. Substantial evidence has been accumulated in the literature during the last couple of years that renders the SIC diagnostic criteria proposed from Mayo Clinic obsolete. In this paper we offer a new set of clinical criteria which we believe better defines the SIC syndrome. Based on the data from the newly established national SIC registry in Sweden, we estimate that as many as 1500--2000 patients annually develop the advanced stage of SIC in our country. It is plausible to assume that the true incidence of SIC is generally much higher if we accept the fact that subclinical and milder forms of SIC in the population do not come to medical attention and that SIC is often mistaken for an acute coronary syndrome. SIC may therefore be the most common form of non-ischemic cardiomyopathy in Sweden and elsewhere. [ABSTRACT FROM AUTHOR]

The pleiotropic action of ticagrelor, with effects in addition to platelet inhibition, has been shown to improve endothelial function in patients with coronary artery disease. These positive effects are possibly adenosine mediated. This study investigated the association of ticagrelor therapy and coronary artery flow reserve in survivors of myocardial infarction (MI). This was an exploratory, cross-sectional, open substudy of PROFLOW. High-risk individuals with a history of MI were identified. Coronary flow reserve (CFR) was measured non-invasively in the left anterior descending artery using transthoracic Doppler echocardiography. Coronary flow velocity was measured at rest and at maximal flow after induction of hyperaemia by intravenous infusion of adenosine at 140 μg/kg/min. Patients receiving ticagrelor (n=75) were compared with those not receiving ticagrelor (n=506), using simple and multiple linear regression models. Most patients in both groups were treated with aspirin (97% in the ticagrelor and 94% in the non-ticagrelor group). Adjustment for traditional risk factors was conducted. The mean age at study inclusion was 68.5±6.8 years, and most patients were male (81.8%). The simple linear regression analysis showed ticagrelor treatment to be significantly associated with increased CFR: ticagrelor 2.95±0.76 (mean±SD), non-ticagrelor 2.70±0.77, (coefficient 0.25; 95% CI 0.063–0.438; p=0.009). This association was significant in two of the three multiple linear regression models with increasing numbers of variables: Model 1 (0.28; 0.06–0.50; p=0.014), Model 2 (0.26; 0.03–0.48; p=0.025), and borderline significant in Model 3 (0.21; –0.01 to 0.43; p=0.058). Ticagrelor treatment was associated with increased CFR in this high-risk population. Increased CFR may be a clinically important therapeutic effect of ticagrelor in addition to platelet inhibition. [ABSTRACT FROM AUTHOR]

Background/aim Sudden cardiac arrest (SCA) has a substantial mortality rate and the acute coronary syndrome constitutes the major cause. Post-resuscitation electrocardiogram ST-elevation SCA (STE-SCA) is a strong indication for emergency coronary angiography, but the role of early angiography and PCI in patients without ST-elevation (NSTE-SCA) remains to be established. This paper aimed to describe this patient group and evaluate the prognostic effect of early PCI in a large nationwide cohort of NSTE-SCA patients undergoing coronary angiography. Methods Data from SCAAR (Swedish Coronary Angiography and Angioplasty Registry) and RIKS-HIA (Register of Information and Knowledge about Swedish Heart Intensive Care Admissions) on 4308 SCA patients in Sweden between 2005 and 2016 were descriptively analyzed and related to mortality within 30-days in both unadjusted and adjusted analyses using Cox proportional hazard models. Results NSTE-SCA patients had more often serious comorbidities than STE-SCA patients. Among NSTE-SCA patients, 36.4% had no significant coronary artery stenosis while severe coronary stenosis (≥90%) was present in 43.9% (1271/2896). In NSTE-SCA patients with significant stenosis (≥90%), PCI was performed in 59.2% (753/1271) with an increased unadjusted 30-day mortality (40.9% vs. 32.7%; p = .011). However, after adjustments for confounders, no difference in mortality was observed (hazard ratio 1.07; 95% CI 0.84–1.36; p = .57). Conclusion In resuscitated SCA patients without ST-elevation who underwent coronary angiography, this large retrospective study found severe coronary artery stenosis in 43.9% but found no clear benefit of early PCI. Prospective randomized controlled trials are needed to accurately define the role of coronary angiography and PCI in post-resuscitation care. [ABSTRACT FROM AUTHOR]

Introduction: An elevated admission plasma glucose (APG) during an acute coronary syndrome (ACS) often reflects undetected diabetes (DM). We investigate the prognostic impact of APG in patients with ACS treated with early PCI and new generation drug-eluting stents. Methods: Patients (n=5309) with established DM and patients without previously known DM with a reported APG, included in the VALIDATE trial 2014-2016, were followed for 4-MACE (mortality, myocardial infarction, stroke, heart failure) within 180 days. Event rates were analyzed by glucose categories. Known DM was defined as reported DM and/or DM treatment at discharge. Patients without DM were categorized by APG into four categories according to WHO criteria for hyperglycemia and DM; I: APG <6.1 mmol/L, II: 6.1-6.9 mmol/L, III: 7.0-11.0 mmol/L, IV: >11.0 mmol/L. Odds ratios (OR) were calculated in a logistic regression model adjusting for age, gender, previous myocardial infarction and indication for PCI (STEMI or non-STEMI). Results: Mean age was 67 ±11 years. Mean APG was 11.6 ±4.8 and 7.0 ±1.7 mmol/L in those with and without DM, respectively. Among those without DM 26.5% (n=1406) had glucose levels in group I, 19.7% (n=1048) in group II, 30.4% (n=1616) in group III and 2.2% (n=115) in group IV. Previously known DM was present in 21.2% (n=1124). 4-MACE increased by increasing APG levels (Figure, p-value for trend <0.001) while bleeding complications did not differ significantly (9.1%, 8.5%, 8.4%, 12.2% and 8.5% respectively). After adjustment, 4-MACE OR (95% CI) was highest for group IV 3.59 (1.99-6.50) compared to the lowest APG group. Randomization to bivalirudin vs. heparin did not influence the composite endpoint of bleeding, myocardial infarction or death in the DM group (p-value 0.82 for interaction) nor 4-MACE; OR 0.81 (95% CI 0.50-1.28, p-value 0.36 for interaction). Conclusions: In a well-treated contemporary population of ACS patients 32.6% of those without DM had elevated APG levels and with greater risk for clinical events already within 180 days. Event rate increased by increasing APG levels. These findings highlight the importance of searching for undetected DM in the setting of ACS and that new treatment strategies are warranted to improve outcome. [ABSTRACT FROM AUTHOR]