Daily Cardiology Research Analysis

BACKGROUND: Catheter-based closure of the left atrial appendage is an alternative to oral anticoagulation for stroke prevention in patients with atrial fibrillation. The effectiveness of this strategy, as compared with physician-directed best medical care, in patients at high risk for stroke and bleeding is unknown. METHODS: In this multicenter randomized trial conducted in Germany, we assigned patients with atrial fibrillation and a high risk of stroke and bleeding to undergo left atrial appendage closure or to receive physician-directed best medical care (including direct oral anticoagulants, if eligible). The primary end point, tested for noninferiority, was a composite of stroke (ischemic or hemorrhagic), systemic embolism, major bleeding, or cardiovascular or unexplained death, assessed in a time-to-event analysis. The noninferiority margin was a hazard ratio of 1.3. RESULTS: A total of 912 adult patients underwent randomization. The primary end-point analysis included 446 patients who were assigned to undergo left atrial appendage closure (device group) and 442 who were assigned to physician-directed best medical care (medical-therapy group). The mean (±SD) age was 77.9±7.1 years; 38.6% of the patients were women, the mean CHA CONCLUSIONS: Among patients with atrial fibrillation at high risk for stroke and bleeding, left atrial appendage closure was not noninferior to physician-directed best medical care with regard to a composite end point of stroke, systemic embolism, major bleeding, or cardiovascular or unexplained death. (Funded by the German Center for Cardiovascular Research; CLOSURE-AF ClinicalTrials.gov number, NCT03463317.).

IMPORTANCE: Premature onset of menopause is associated with increased short-term risk of coronary heart disease (CHD), but the associated long-term CHD risk and whether this differs by self-identified race are not known. OBJECTIVE: To calculate lifetime risk estimates of incident CHD and to estimate years lived free of and with CHD by premature menopause status stratified by self-identified race. DESIGN, SETTING, AND PARTICIPANTS: This prospective population-based cohort study was conducted with 163 600 person-years of follow-up, from 1964 to 2018. Individual-level data from postmenopausal women (aged 55-69 years) who self-identified their race as Black or White across 6 US cohorts were included. All participants were free of CHD at baseline and had data on menopausal status and CHD outcomes. Individuals who self-reported surgically induced menopause were excluded. EXPOSURE: Premature onset of natural menopause (age <40 years). MAIN OUTCOME AND MEASURES: The primary outcome was CHD (fatal and nonfatal myocardial infarction). The following analyses were performed: (1) modified Kaplan-Meier analysis to estimate lifetime risks, (2) adjusted competing Cox models to estimate joint cumulative risks for CHD or non-CHD death, and (3) Irwin restricted mean survival time to estimate mean years lived free of CHD and with CHD. RESULTS: Of the 3522 Black women and 6514 White women included, mean (SD) age at baseline was 61.2 (4.3) years and 60.0 (4.4) years, respectively. Premature natural menopause occurred more frequently in Black women (545 [15.5%]) compared with White women (313 [4.8%]). Premature menopause was associated with a higher lifetime risk of incident CHD, with hazard ratios of 1.41 (95% CI, 1.04-1.90) for Black women and 1.39 (95% CI, 1.03-1.87) for White women. Mean years lived free of CHD were 18.2 years (95% CI, 17.5-18.9) for Black women with premature menopause compared to 19.1 years (95% CI, 18.8-19.4) for Black women without premature menopause; a similar pattern was seen in White women with and without premature menopause, but neither met statistical significance. CONCLUSIONS AND RELEVANCE: In this cohort study, premature menopause was associated with 40% higher lifetime risk of CHD in Black and White women. This suggests that premature onset of menopause is an important risk-enhancing factor for lifetime risk and should be routinely assessed in clinical practice to consider intensification of preventive efforts.

BACKGROUND: Clopidogrel may have ischemic benefit over aspirin as long-term monotherapy in patients receiving percutaneous coronary intervention. METHODS: Both the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy-2) and STOPDAPT-2 ACS (Short and Optimal Duration of Dual Antiplatelet Therapy-2 Study for the Patients With Acute Coronary Syndrome) were multicenter, open-label, adjudicator-blinded, randomized clinical trials in Japan, with the same protocol except that the STOPDAPT-2 ACS enrolled patients with acute coronary syndrome, exclusively. The patients after percutaneous coronary intervention with cobalt-chromium everolimus-eluting stents were randomized into 1-month dual antiplatelet therapy followed by clopidogrel monotherapy (clopidogrel group) or 12-month dual antiplatelet therapy followed by aspirin monotherapy (aspirin group). Follow-up duration was 5 years. The clinical effect between clopidogrel and aspirin monotherapy was compared by the 1-year landmark analysis in the STOPDAPT-2 ACS and STOPDAPT-2 total cohort, a pooled cohort of the 2 trials. The primary end point was the composite of cardiovascular end point (cardiovascular death, myocardial infarction, stroke, or definite stent thrombosis) and bleeding end point (Thrombolysis in Myocardial Infarction major/minor). The major secondary end points were each of the cardiovascular composite end point and the bleeding end point. RESULTS: Of 2986 patients (clopidogrel group: 1492, aspirin group: 1494) in the 5-year analysis of the STOPDAPT-2 ACS, 2875 (96.3%) completed follow-up. By the 1-year landmark analysis, clopidogrel group was superior to aspirin group for both the primary end point (6.18% and 8.27%; hazard ratio, 0.75 [95% CI, 0.57-0.997]; CONCLUSIONS: Clopidogrel monotherapy was superior to aspirin monotherapy for cardiovascular outcomes beyond 1 year after percutaneous coronary intervention, without increased bleeding risk. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02619760 and NCT03462498.