Background: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) remains uncertain. We compared short-term (<6-month) DAPT followed by aspirin or P2Y12 inhibitor monotherapy; mid-term (6-month) DAPT; 12-month DAPT; and extended-term (>12-month) DAPT after PCI with DES. Methods: Twenty-four randomized controlled trials were selected using Medline, Embase, Cochrane library, and online databases through September 2019. The co-primary endpoints were myocardial infarction (MI) and major bleeding, which constituted the net clinical benefit. A frequentist network meta-analysis was conducted with random effects model. Results: In 79,073 patients, at a median follow-up of 18 months, extended-term DAPT was associated with a reduced risk of MI compared with 12-month DAPT (absolute risk difference [ARD], -3.8 incident cases per 1000 person-years; relative risk (RR), 0.68 [95% CI, 0.54-0.87]), mid-term DAPT (ARD, -4.6 incident cases per 1000 person-years; RR, 0.61 [0.45-0.83]), and short-term DAPT followed by aspirin monotherapy (ARD, -6.1 incident cases per 1000 personyears; RR, 0.55 [0.37-0.83]), or P2Y12 inhibitor monotherapy (ARD, -3.7 incident cases per 1000 person-years; RR, 0.69 [0.51-0.95]). Conversely, extended-term DAPT was associated with a higher risk of major bleeding compared with all other DAPT groups. Compared with 12-month DAPT, no significant differences in the risks of ischemic endpoints or major bleeding were observed with mid-term or short-term DAPT followed by aspirin monotherapy, except that shortterm DAPT followed by P2Y12 inhibitor monotherapy was associated with a reduced risk of major bleeding. There were no significant differences with respect to mortality between the different DAPT strategies. In acute coronary syndrome (ACS), extended-term compared with 12-month DAPT was associated with a reduced risk of MI without significant increase in the risk of major bleeding. Conclusions: The present network meta-analysis suggests that compared with 12-month DAPT, short-term DAPT followed by P2Y12 inhibitor monotherapy reduces major bleeding after PCI with DES, while extended-term DAPT reduces myocardial infarction at the expense of more bleeding events.

This systematic review examines the level and prevalence of spin in presenting findings that are not statistically significant in published reports of cardiovascular randomized clinical trials (RCTs).

No abstract

Background:The effects of omega-3 fatty acids (FAs), such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, on cardiovascular outcomes are uncertain. We aimed to determine the effectiveness of omega-3 FAs on fatal and non-fatal cardiovascular outcomes and examine the potential variability in EPA vs. EPA +DHA treatment effects. Methods: We searched EMBASE, PubMed, ClinicalTrials.gov, and Cochrane library databases through June 7, 2021. We performed a meta-analysis of 38 randomized controlled trials of omega-3 FAs, stratified by EPA monotherapy and EPA+DHA therapy. We estimated random-effects rate ratios (RRs) with (95% confidence intervals) and rated the certainty of evidence using GRADE. The key outcomes of interest were cardiovascular mortality, non-fatal cardiovascular outcomes, bleeding, and atrial fibrillation (AF). The protocol was registered in PROSPERO (CRD42021227580). Findings: In 149,051 participants, omega-3 FA was associated with reducing cardiovascular mortality (RR, 0.93 [0.88-0.98]; p = 0.01), non-fatal myocardial infarction (MI) (RR, 0.87 [0.81À0.93]; p = 0.0001), coronary heart disease events (CHD) (RR, 0.91 [0.87À0.96]; p = 0.0002), major adverse cardiovascular events (MACE) (RR, 0.95 [0.92À0.98]; p = 0.002), and revascularization (RR, 0.91 [0.87À0.95]; p = 0.0001). The meta-analysis showed higher RR reductions with EPA monotherapy (0.82 [0.68À0.99]) than with EPA + DHA (0.94 [0.89À0.99]) for cardiovascular mortality, non-fatal MI (EPA: 0.72 [0.62À0.84]; EPA+DHA: 0.92 [0.85À1.00]), CHD events (EPA: 0.73 [0.62À0.85]; EPA+DHA: 0.94 [0.89À0.99]), as well for MACE and revascularization. Omega-3 FA increased incident AF (RR, 1.26 [1.08À1.48]). EPA monotherapy vs. control was associated with a higher risk of total bleeding (RR: 1.49 [1.20À1.84]) and AF (RR, 1.35 [1.10À1.66]). Interpretation: Omega-3 FAs reduced cardiovascular mortality and improved cardiovascular outcomes. The cardiovascular risk reduction was more prominent with EPA monotherapy than with EPA+DHA.

Background In 1993, the US Food and Drug Administration established guidelines to increase diversity by sex and race/ethnicity of participants in clinical trials supporting novel drug approvals. In this study we investigated the 10‐year trends of participation of women and minorities in pivotal trials supporting approval of new molecular entities in cardiometabolic drugs from January 2008 to December 2017. Methods and Results A list of new molecular entities was abstracted from publicly available data at Drugs@Fda . Sex and race/ethnicity data were collected from trial publications. Linear regression analysis was performed to assess the relation between drug approval year and proportion of women and minorities enrolled. Thirty‐five novel cardiovascular (n=24) and diabetes mellitus (n=11) drugs were approved by the US Food and Drug Administration during the study period. The median number of participants supporting each drug was 5930 (interquartile range, 3175–10 942). Women represented 36% (n=108 052) of trial participants (n=296 163). Women were underrepresented compared with their proportion of the disease population in trials of coronary heart disease (participation‐to‐prevalence ratio, 0.52), heart failure (participation‐to‐prevalence ratio, 0.58), and acute coronary syndrome (participation‐to‐prevalence ratio, 0.68). Among trial participants, 81% were white, 4% black, 12% Asian, and 11% Hispanic/Latino. There was no significant association between enrollment of women ( P =0.29) or underrepresented minorities ( P =0.45) with the drug approval year. Conclusions Over the past decade (2008–2017), women and minorities, particularly blacks, have continued to be inadequately represented in pivotal cardiometabolic clinical trials that support US Food and Drug Administration approval of new molecular entities. This may have major implications in determining efficacy of such therapies in these groups, and may impair generalizability of trial results to routine clinical practice.

Background Atherosclerotic cardiovascular disease ( ASCVD ) accounts for approximately one third of deaths in women. Although there is an established relationship between positive patient experiences, health‐related quality of life, and improved health outcomes, little is known about gender differences in patient‐reported outcomes among ASCVD patients. We therefore compared gender differences in patient‐centered outcomes among individuals with ASCVD . Methods and Results Data from the 2006 to 2015 Medical Expenditure Panel Survey, a nationally representative US sample, were used for this study. Adults ≥18 years with a diagnosis of ASCVD , ascertained by International Classification of Diseases, Ninth Revision ( ICD‐9) codes and/or self‐reported data, were included. Linear and logistic regression were used to compare self‐reported patient experience, perception of health, and health‐related quality of life by gender. Models adjusted for demographics, socioeconomic status, and comorbidities. There were 21 353 participants included, with >10 000 (47%‐weighted) of the participants being women, representing ≈11 million female adults with ASCVD nationwide. Compared with men, women with ASCVD were more likely to experience poor patient–provider communication (odds ratio 1.25 [95% confidence interval 1.11–1.41]), lower healthcare satisfaction (1.12 [1.02–1.24]), poor perception of health status (1.15 [1.04–1.28]), and lower health‐related quality of life scores. Women with ASCVD also had lower use of aspirin and statins, and greater odds of ≥2 Emergency Department visits/y. Conclusions Women with ASCVD were more likely to report poorer patient experience, lower health‐related quality of life, and poorer perception of their health when compared with men. These findings have important public health implications and require more research towards understanding the gender‐specific differences in healthcare quality, delivery, and ultimately health outcomes among individuals with ASCVD .

IMPORTANCE Interpreting randomized clinical trials (RCTs) and their clinical relevance is challenging when P values are either marginally above or below the P = .05 threshold. OBJECTIVE To use the concept of reverse fragility index (RFI) to provide a measure of confidence in the neutrality of RCT results when assessed from the clinical perspective.

IMPORTANCE Randomized clinical trials (RCTs) of lipid-lowering therapies form the evidence base for national and international guidelines. However, concerns exist that women and older patients are underrepresented in RCTs. OBJECTIVE To determine the trends of representation of women and older patients (Ն65 years) in RCTs of lipid-lowering therapies from 1990 to 2018. DATA SOURCES The electronic databases of MEDLINE and ClinicalTrials.gov were searched from January 1990 through December 2018. STUDY SELECTION RCTs of lipid-lowering therapies with sample sizes of at least 1000 patients and follow-up periods of at least 1 year were included. DATA EXTRACTION AND SYNTHESIS Two independent investigators abstracted the data on a standard data collection form. MAIN OUTCOMES AND MEASURES Patterns of representation of women and older adults were examined overall in lipid-lowering RCTs and according to RCT-level specific characteristics. The participation-to-prevalence ratio (PPR) metric was used to estimate the representation of women compared with their share of disease burden. RESULTS A total of 60 RCTs with 485 409 participants were included. The median (interquartile range) number of participants per trial was 5264 (1062-27 564). Overall, representation of women was 28.5% (95% CI, 24.4%-32.4%). There was an increase in the enrollment of women from the period 1990 to 1994 (19.5%; 95% CI, 18.4%-20.5%) to the period 2015 to 2018 (33.6%; 95% CI, 33.4%-33.8%) (P for trend = .01). Among common limiting factors were inclusion of only postmenopausal women or surgically sterile women (28.3%; 95% CI, 18.5%-40.7%) or exclusion of pregnant (23.3%; 95% CI, 14.4%-35.4%) and lactating (16.6%; 95% CI, 9.3%-28.1%) women. Women were underrepresented compared with their disease burden in lipid RCTs of diabetes (PPR, 0.74), heart failure (PPR, 0.27), stable coronary heart disease (PPR, 0.48), and acute coronary syndrome (PPR, 0.51). Only 23 RCTs with 263 628 participants reported the proportion of older participants. Overall representation of older participants was 46.7% (95% CI, 46.5%-46.9%), which numerically increased from 31.6% (95% CI, 30.8%-32.3%) in the period 1995 to 1998 to 46.2% (95% CI, 46.0%-46.5%) in the period 2015 to 2018 (P for trend = .43). A total of 53.0% (95% CI, 41.8%-65.3%) and 36.6% (95% CI, 25.6% to 49.3%) trials reported outcomes according to sex and older participants, respectively, which did not improve over time. (continued) Key Points Question Are women and older participants adequately represented in randomized clinical trials of lipidlowering therapy? Findings In this systematic review of 60 trials with 485 409 participants that were conducted between 1990 and 2018, there was a modest increase in the enrollment of women (from 19.5% to 33.6%) and older participants (from 31.6% to 46.2%); however, overall representation was low (28.5% women and 46.7% older adults). Women were underrepresented in trials compared with their relative disease burden. Meaning The results of this study suggest that despite ongoing ef...