Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular disease

Fixed-dose combination (FDC) therapy, also known as polypill therapy, targets risk factors for atherosclerotic cardiovascular disease (ASCVD) and has been proposed as a strategy to reduce global ASCVD burden. Here we conducted a systematic search for relevant studies from 2016-2022 to assess the effects of FDC therapy for prevention of ASCVD. The studies selected include randomized trials evaluating FDC therapy with at least one blood pressure-lowering drug and one lipid-lowering drug. The study data were independently extracted, the quality of evidence was appraised by multiple reviewers and effect estimates were pooled using a fixed-effect meta-analysis when statistical heterogeneity was low to moderate. The main outcomes of the analysis were all-cause mortality, fatal and nonfatal ASCVD events, adverse events, systolic blood pressure, low-density lipoprotein cholesterol and adherence. Among 26 trials (n = 27,317 participants, 43.2% female and mean age range 52.9-76.0), FDC therapy was associated with lower low-density lipoprotein cholesterol and systolic blood pressure, with higher rates of adherence and adverse events in both primary and mixed secondary prevention populations. For studies with a mostly primary prevention population, FDC therapy was associated with lower risk of all-cause mortality by 11% (5.6% versus 6.3%; relative risk (risk ratio) of 0.89; 95% confidence interval 0.78 to 1.00; I² = 0%; four trials and 16,278 participants) and risk of fatal and nonfatal ASCVD events by 29% (6.1% versus 8.4%; relative risk (risk ratio) of 0.71; 95% confidence interval 0.63 to 0.79; I² = 0%; five trials and 15,503 participants). One adequately powered trial in an exclusively secondary prevention population showed that FDC therapy reduced the risk of major adverse cardiovascular events by 24%. These findings support adoption and implementation of polypills to lower risk for all-cause mortality and ASCVD.