Yazgi Habib, Mattikalli Shivani, Fang Brian, Heselton Hannah, Ssentongo Paddy, Farbaniec Michael
Department of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, United States.
Division of Infectious Diseases, Department of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, United States.
Front Cardiovasc Med. 2025 Jun 9;12:1558579. doi: 10.3389/fcvm.2025.1558579. eCollection 2025.
Cardiovascular disease is the leading cause of mortality and morbidity worldwide, and polypills have established efficacy in preventing poor outcomes. However, evidence on the optimal polypill combination is lacking. The objective of the study is to estimate the optimal polypill combination that maximizes cardiovascular outcomes.
MEDLINE/PubMed, Scopus, and Cochrane Database of Systematic Reviews databases were searched from January 1, 1960, to March 30, 2025. Studies that provided data on the association between polypill and cardiovascular outcomes were included. We estimated the effect of various polypill combinations by random-effects meta-analyses using the generic inverse variance method. Subgroup and meta-regression analyses were conducted to explore potential effect modification in the association between polypill combinations and cardiovascular outcomes.
Thirty studies comprising 35,833 individuals met the inclusion criteria from 6 continents. The estimated pooled effects of polypill use on major adverse cardiovascular events (MACE), cardiovascular death, and all-cause mortality were RR 0.78 (95% CI, 0.63-0.97), 0.75 (95% CI, 0.63-0.89), 0.88 (95% CI, 0.79-0.98), respectively. The pooled relative risk of MACE outcome was 21% lower in combination of 4 or more pills [0.79 (95% CI, 0.55-1.15), = 6 studies] vs. to 22% and 3 or less combination of medication classes (RR: 0.78 95% CI: 0.70-0.86), = 4 studies). Polypill combinations containing moderate or high-intensity statins were associated with lower risk of MACE outcomes RR 0.79 95% CI: 0.70-0.97), = 2 studies compared to combinations with low-intensity statins RR 0.78 95% CI: 0.59-1.03, = 8). All polypills for MACE outcomes contained RAAS inhibitors. Calcium channel blockers, RAAS inhibitors and diuretics-containing polypills were associated with the highest reduction in blood pressure. Certainty of evidence for MACE ranged from low to high, with most trials rated as moderate to high.
In this meta-analysis, polypills with 3 cardiovascular classes that contain a high-intensity statins, aspirin and RAAS inhibitors appeared to have greater reduction in MACE outcomes. The presence of a diuretic and a calcium channel blocker in the polypill was associated with greater reductions in systolic and diastolic blood pressure.
心血管疾病是全球死亡和发病的主要原因，而复方制剂在预防不良结局方面已证实有效。然而，关于最佳复方制剂组合的证据尚缺。本研究的目的是评估能使心血管结局最大化的最佳复方制剂组合。
检索了MEDLINE/PubMed、Scopus和Cochrane系统评价数据库，时间范围为1960年1月1日至2025年3月30日。纳入提供复方制剂与心血管结局之间关联数据的研究。我们采用通用逆方差法通过随机效应荟萃分析估计各种复方制剂组合的效果。进行亚组分析和meta回归分析以探讨复方制剂组合与心血管结局之间关联中的潜在效应修饰。
来自6个大洲的30项研究（共35,833名个体）符合纳入标准。复方制剂使用对主要不良心血管事件（MACE）、心血管死亡和全因死亡率的估计合并效应分别为RR 0.78（95%CI，0.63 - 0.97）、0.75（95%CI，0.63 - 0.89）、0.88（95%CI，0.79 - 0.98）。4种或更多药物组合的MACE结局合并相对风险比2种或更少药物类别组合低21%[0.79（95%CI，0.55 - 1.15），n = 6项研究]，而2种或更少药物类别组合的RR为0.78（95%CI：0.70 - 0.86），n = 4项研究）。与低强度他汀类药物组合[RR 0.78（95%CI：0.59 - 1.03），n = 8项研究]相比，含中等或高强度他汀类药物的复方制剂组合与较低的MACE结局风险相关[RR 0.79（95%CI：0.70 - 0.97），n = 2项研究]。所有用于MACE结局的复方制剂都含有肾素 - 血管紧张素 - 醛固酮系统（RAAS）抑制剂。含钙通道阻滞剂、RAAS抑制剂和利尿剂的复方制剂与血压降低幅度最大相关。MACE结局的证据确定性从低到高不等，大多数试验评级为中等至高。
在这项荟萃分析中，包含高强度他汀类药物、阿司匹林和RAAS抑制剂的3种心血管药物类别的复方制剂似乎能更大程度降低MACE结局。复方制剂中存在利尿剂和钙通道阻滞剂与收缩压和舒张压的更大降低相关。
