Supplementary Material for: Fixed-dose Combination (Polypill) for Myocardial Infarction Prevention: A Meta-analysis of Randomized Controlled Trials

Aims: Myocardial infarction (MI) is one of the leading causes of death from cardiovascular diseases (CVD). Despite various drugs and treatments, the outcomes have often been unsatisfactory. The purpose of this meta-analysis aims to analyze the effects of polypill intervention on the incidence of MI and the related risk factors, blood pressure and blood lipids. Methods: We conducted a systematic search of appropriate randomized controlled trials (RCTs) in various databases, utilizing preset search terms. Then, we performed a meta-analysis of individual participant data, including studies that investigated the effectiveness of polypill (a fixed-dose combination drug) as compared to usual care in preventing MI. The primary outcomes are MI, CVD mortality, MACE and all-cause mortality. Secondary outcomes include blood pressure levels (systolic blood pressure (SBP), diastolic blood pressure (DBP)) and serum lipid levels (total cholesterol (TC), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL). Results: A total of 14 trials (N = 59,346) were included, with a mean age of 63.2 ± 10.0 years. The results showed that compared to the usual care group, polypill group was associated with a significant reduction of the incidence of MI (OR = 0.76; 95% CI: 0.59 to 0.99; p = 0.04) and MACE (OR = 0.79; 95%CI: 0.65 to 0.97; p = 0.03). The risk reduction for CVD mortality (OR = 0.85; 95%CI :0.65 to 1.11; p = 0.20) and all-cause mortality (OR = 0.99; 95%CI: 0.95 to 1.03; p = 0.59) did not reach statistical significance contrast with the usual care group. Participants who were in polypill group was observed that the change of SBP level (SMD = -0.13; 95%CI: -0.25 to 0.00; p = 0.04), DBP level (SMD = -0.13; 95%CI: -0.19 to -0.06; p = 0.00) and LDL level (SMD = -0.21; 95%CI: -0.36 to -0.06; p = 0.01) reached statistical significance. However, the change of HDL level (SMD = -0.01; 95%CI: -0.06 to 0.04; p = 0.62) and TC level (SMD = -0.15; 95%CI: -0.32 to 0.01; p = 0.06) did not show remarkable difference. Conclusion: These findings suggested that polypill not only is highly effective for preventing MI and reducing the incidence of MACE, but also can lower blood pressure levels and blood lipid levels.