Compliance with the prescription of recommended medical therapy in trials comparing six versus 12 months or longer dual antiplatelet therapy: A systematic review and meta-analysis

Abstract

Certain randomized controlled trials suggested that six months’ dual antiplatelet therapy (DAPT) might be equally effective and probably a safer approach compared with 12 months’ therapy following percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). These findings have influenced current professional guidelines which now endorse DAPT for 6–12 months following DES based PCI. However, the impact of concomitant guideline directed medical therapy (GDMT) such as statins, beta-blockers, angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs)) on study outcomes in such trials is often overlooked. In a recent meta-analysis of five revascularization trials, compliance with GDMT was shown to be suboptimal and was significantly lower after coronary artery bypass grafting than PCI. Based on these observations, we conducted a meta-analysis to compare the differences in GDMT in trials comparing six months’ versus 12 months’ DAPT after PCI. Four trials reporting concurrent GDMT (statins, beta-blockers and ACEI/ARB) at least at baseline or discharge were selected using MEDLINE, EMBASE and CENTRAL (inception–10 October 2018) (Table 1). Compliance rates for individual therapies were calculated as percent of subjects prescribed each drug at baseline or discharge. The ‘‘compliance gap’’ was obtained by calculating the difference in compliance rates of study groups. The estimates were reported as random effects risk differences with 95% confidence intervals. Q statistics and I statistics were used to assess heterogeneity. Quality assessment of trials was done on Cochrane risk of bias tool. The literature search, data extraction and bias risk assessment was done by two authors (SUK and MSK) independently. Moment of methods meta regression analysis was conducted between GDMT and all-cause mortality and cardiovascular outcomes. Statistical significance was set at 5%. Comprehensive Meta-Analysis (version 3) was used for meta-analysis. Over all compliance with GDMT at baseline was 84.0% (75–90%; p< 0.001). Statins had the highest compliance rates: 90.7% (80.8–95.7%, p< 0.001), followed by ACEI/ARB: 81.5% (75.5–86.3%, p< 0.001) and beta-blockers: 79.8% (70.5–86.7%, p< 0.001). There was a slight reduction in prescription rates of medical therapy at discharge: GDMT: 77.5% (69.6–83.9%, p< 0.001], statins: 87.8% (83.9–90.9%, p< 0.001), beta-blockers: 71.9% (69.6–83.9%, p< 0.001(ACEI/ARB: 72.4% (60.9–81.5%, p< 0.001). The compliance rates for proton pump inhibitors (PPIs) at baseline: 31.5% (21.5–43.6%, p< 0.001) and discharge: 34.6% (32.5–36.7%, p< 0.001) were lowest. There were no significant differences between compliance rates of medical therapy among six versus 12 months’ DAPT groups (Figure 1). Hence, the absolute difference in GDMT did not result in significant change in all-cause mortality (slope: 0.00009, p1⁄4 0.58), myocardial infarction (slope: 0.00017, p1⁄4 0.49), stroke (slope: 0.00014, p1⁄4 0.43) and stent thrombosis (slope: 0.00006, p1⁄4 0.62). Overall GDMT compliance in both arms of these trials was better than compliance rates reported in meta-analysis of revascularization trials ( 53% to 67%). The comparable compliance rates in both the groups also validate the impression that cardiovascular