Quiz Ref ID Consistent evidence has shown that statins reduce total cardiovascular events, and that further lowering of low-density lipoprotein cholesterol (LDL-C) levels by intensifying statin therapy, adding ezetimibe, or adding a proprotein convertase subtilisin/kexin type 9 (PCSK9)-inhibiting monoclonal antibody provides incremental additional reduction in cardiovascular risk.^1-6 However, there is less consistency in the magnitude of the reductions in individual mortality and cardiovascular end points among the various trials. Total and cardiovascular mortality benefits were observed in several placebo-controlled statin cardiovascular outcomes trials as well as in meta-analyses of statin trials.^1,7-9 In contrast, no reduction in cardiovascular mortality was observed in 5-year trials of moderate- vs high-intensity statin therapy or in trials of ezetimibe or evolocumab added to background statin therapy.^2,3,10-12 Understanding differences in treatment effects across clinical trials may influence estimates of treatment benefit, have an important effect on guideline recommendations and clinical trial design, and has already had a significant influence on cost-effectiveness analyses and accessibility decisions.^13-15

Guidelines recommend statins as first-line therapy for dyslipidemia. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new lipid-lowering approach. To assess the efficacy and safety of PCSK9 antibodies in adults with hypercholesterolemia. MEDLINE, PubMed Central, and Google Scholar; conference proceedings; and the ClinicalTrials.gov registry through 4 April 2015. Phase 2 or 3 randomized, controlled trials (RCTs) comparing treatment using PCSK9 antibodies with no anti-PCSK9 therapy in adults with hypercholesterolemia. Two investigators independently extracted data on study characteristics and lipid and clinical outcomes, and rated risk of bias of trials. Prespecified primary end points were all-cause and cardiovascular mortality. Twenty-four RCTs comprising 10 159 patients were included. Compared with no antibody, treatment with PCSK9 antibodies led to marked reductions in low-density lipoprotein cholesterol levels (mean difference, −47.49% [95% CI, −69.64% to −25.35%]; P < 0.001] and other atherogenic lipid fractions, and it reduced all-cause mortality (odds ratio [OR], 0.45 [CI, 0.23 to 0.86]; P = 0.015; heterogeneity P = 0.63; I² = 0%) and cardiovascular mortality (OR, 0.50 [CI, 0.23 to 1.10]; P = 0.084; heterogeneity P = 0.78; I² = 0%). The rate of myocardial infarction was significantly reduced with use of PCSK9 antibodies (OR, 0.49 [CI, 0.26 to 0.93]; P = 0.030; heterogeneity P = 0.45; I² = 0%), and increases in the serum creatine kinase level were reduced (OR, 0.72 [CI, 0.54 to 0.96]; P = 0.026; heterogeneity P = 0.65; I² = 0%). Serious adverse events did not increase with administration of PCSK9 antibodies. Results were derived from study-level data rather than patient-level data, and clinical outcome data are rare. PCSK9 antibodies seem to be safe and effective for adults with dyslipidemia. CRC 1116 Masterswitches in Myocardial Ischemia, German Research Council DFG.

Objective To assess the benefits and risks of short term (12 months) dual antiplatelet therapy (DAPT) versus standard 12 month therapy, following percutaneous coronary intervention with drug eluting stents. Design Meta-analysis of randomised controlled trials. Data sources PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Scopus, Web of Science, Cochrane Library, and major congress proceedings, searched from 1 January 2002 to 16 February 2015. Review methods Trials comparing short term (12 months) DAPT regimens with standard 12 month duration of therapy. Primary outcomes were cardiovascular mortality, myocardial infarction, stent thrombosis, major bleeding, and all cause mortality. Results 10 randomised controlled trials (n=32 287) were included. Compared to 12 month DAPT, a short term course of therapy was associated with a significant reduction in major bleeding (odds ratio 0.58 (95% confidence interval 0.36 to 0.92); P=0.02) with no significant differences in ischaemic or thrombotic outcomes. Extended versus 12 month DAPT yielded a significant reduction in the odds of myocardial infarction (0.53 (0.42 to 0.66); P<0.001) and stent thrombosis (0.33 (0.21 to 0.51); P<0.001), but more major bleeding (1.62 (1.26 to 2.09); P<0.001). All cause but not cardiovascular death was also significantly increased (1.30 (1.02 to 1.66); P=0.03). Conclusions Compared with a standard 12 month duration, short term DAPT (12 months) could be considered. The increase in all cause but not cardiovascular death with extended DAPT requires further investigation.

Background—: Heart failure with reduced ejection fraction caused by ischemic heart disease is associated with increased morbidity and mortality. It remains unclear whether revascularization by either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) carries benefits or risks in this group of stable patients compared with medical treatment. Methods and Results—: We performed a meta-analysis of available studies comparing different methods of revascularization (PCI or CABG) against each other or medical treatment in patients with coronary artery disease and left ventricular ejection fraction ≤40%. The primary outcome was all-cause mortality; myocardial infarction, revascularization, and stroke were also analyzed. Twenty-one studies involving a total of 16 191 patients were included. Compared with medical treatment, there was a significant mortality reduction with CABG (hazard ratio, 0.66; 95% confidence interval, 0.61–0.72; P <0.001) and PCI (hazard ratio, 0.73; 95% confidence interval, 0.62–0.85; P <0.001). When compared with PCI, CABG still showed a survival benefit (hazard ratio, 0.82; 95% confidence interval, 0.75–0.90; P <0.001). Conclusions—: The present meta-analysis indicates that revascularization strategies are superior to medical treatment in improving survival in patients with ischemic heart disease and reduced ejection fraction. Between the 2 revascularization strategies, CABG seems more favorable compared with PCI in this particular clinical setting.