Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1199-1209 |
| Number of pages | 11 |
| Journal | Nature Medicine |
| Volume | 30 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2024 |
Funding
We thank the investigators of the PolyIran-Liver trial for sharing selected disaggregated data to allow our team to standardize definitions of ASCVD events in this systematic review and meta-analysis. We thank A. Hively for his contributions in manuscript reviewing. The study received no funding. A.A. is supported by the NIH/NHLBI grant K99HL157687 and has received funding from grant 2020144 from the Doris Duke Charitable Foundation. M.D.H. has received travel support from the World Heart Federation. M.D.H. and A.R. have an appointment at The George Institute for Global Health, which has a patent, license and has received investment funding with intent to commercialize fixed-dose combination therapy through its social enterprise business, George Medicines. George Health Enterprises Pty Ltd, the social enterprise arm of the George Institute for Global Health (TGIGH), has received investment to develop fixed-dose combination products containing aspirin, statin and BP-lowering drugs. The George Institute for Global Health holds and have filed applications for combination products for the treatment of hypertension and diabetes, and A.R. is listed as one of the inventors (granted: US 10,369,15; US 10,799,487; US 10,322,117; US 11,033,544; and US 11,478,462 and pending: US 17/932,982; US 18/446,268; US 17/598,122; and US 17/317,614). A.R. is seconded part-time to George Medicines Pty Ltd, a subsidiary of George Health Enterprises. A.R. does not have a personal financial interest in these patents or products. M.D.H. and A.A. have pending patents for heart failure polypills. The other authors declare no competing interests.
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
