Sources of Heterogeneity in the Efficacy of Statins for Primary Prevention of Cardiovascular Diseases: A Systematic Review with Meta-Regression and Meta-Analysis of Within-Study Subgroup Differences
Long Y, Liu J, Cai J, Zhuang Q, Cai T, Zhou J, Chai S, Lin T, Yang Z
Cardiovascular drugs and therapy · 0 citas
Cómo se estudió
- Diseño
- Metaanálisis (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- Shenzhen Science and Technology Innovation Program
- Gobierno
- National Natural Science Foundation of China
- Gobierno
- Shenzhen Medical Research Fund
- Subvenciones
- Shenzhen Science and Technology Innovation Program (JCYJ20220530154409021)
Según 3 financiadores declarados.
Publicación
- Publicado
- 2026-05-02 · Cardiovasc Drugs Ther · vol. 40 · número 5 · págs. 2049–2060
- Editorial
- Springer Science+Business Media
- Citado
- 0 citas · más que el 24% de estudios similares · 0.0× el promedio de su campo
- Referencias
- 0 trabajos
- Acceso
- De pago
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Cancer, Lipids, and Metabolism · Meta-analysis and systematic reviews
- Palabras clave
- statins, primary prevention, cardiovascular disease, treatment effect heterogeneity, major adverse cardiovascular events, myocardial infarction, stroke, cardiovascular mortality, lipid-lowering therapy, cardiovascular risk stratification, risk of bias
- MeSH
- humans, cardiovascular diseases, hydroxymethylglutaryl-coa reductase inhibitors, treatment outcome, primary prevention, female, randomized controlled trials as topic, treatment effect heterogeneity
9 autores
- Yujun Long🇨🇳Chinese Academy of Sciences; Shenzhen Institutes of Advanced Technology; University of Chinese Academy of Sciences; Shenzhen University of Advanced Technology
- Jianzhao Liu🇨🇳Chinese Academy of Sciences; Southern University of Science and Technology; Shenzhen Institutes of Advanced Technology; Shenzhen University of Advanced Technology
- Jiaxin Cai🇨🇳University of Nottingham Ningbo China; Shenzhen University of Advanced Technology
- Qiongqi Zhuang🇨🇳Shenzhen University of Advanced Technology
- Ting Cai🇬🇧University of Oxford
- Junwen Zhou🇬🇧University of Oxford
- Sanbao Chai🇨🇳Peking University International Hospital
- Tengfei Lin🇨🇳 · autor de correspondenciaChinese Academy of Sciences; Shenzhen Institutes of Advanced Technology; Southern Medical University
- Zhirong Yang🇨🇳 · autor de correspondenciaChinese Academy of Sciences; Shenzhen Institutes of Advanced Technology; Shenzhen University of Advanced Technology
Resumen
El texto original del estudio, en el idioma en que se publicó.
Purpose
Evidence regarding sources of heterogeneity in the efficacy of statins for primary prevention of cardiovascular disease (CVD) remains limited. This study aimed to identify trial-level factors contributing to such heterogeneity.
Methods
Relevant studies were systematically identified from a previous systematic review and through searches in PubMed, Embase, and Cochrane up to 20 January 2026. The protocol was registered in PROSPERO (CRD42024579932). Randomized controlled trials (RCTs) in adults without prior CVD that investigated statin treatment were included. Risk of bias was assessed using the Cochrane Risk of Bias tool. Meta-analyses were conducted to pool risk ratios (RRs) and 95% confidence intervals (CIs) for major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, and cardiovascular death. Univariate meta-regression analyses were conducted to assess the impact of trial-level covariates on the effect sizes, expressed as the ratio of risk ratios (RRR). Within-study subgroup differences were meta-analyzed by pooling ratio of effect sizes. Meta-regression analyses were conducted using complete-case trial-level data.
Results
25 RCTs (102,667 participants) were included. Compared to no statin treatment, statin treatment was associated with a reduced risk of MACE (RR, 0.73[95% CI, 0.67 to 0.80], P < 0.001), MI (RR, 0.68[95% CI, 0.60 to 0.77], P < 0.001), stroke (RR, 0.76[95% CI, 0.65 to 0.89], P = 0.001) and cardiovascular death (RR, 0.81[95% CI, 0.71 to 0.95], P = 0.008). Univariate meta-regression indicated that higher baseline total cholesterol (RRR, 1.29 [95% CI, 1.07 to 1.57], P = 0.008), higher low-density lipoprotein cholesterol (LDL-C) (RRR, 1.31 [95% CI, 1.07 to 1.62], P = 0.010), higher triglycerides (RRR, 1.81 [95% CI, 1.17 to 2.81], P = 0.008) and lower statin intensity (RRR, 0.74 [95% CI, 0.59 to 0.94], P = 0.015) were significantly associated with reduced efficacy of statins for stroke prevention at the trial level.
Conclusions
Statin therapy demonstrated consistent efficacy in CVD prevention across diverse populations, except that baseline lipid profiles and statin intensity may represent exploratory, hypothesis-generating signals of potential effect modification for stroke prevention, warranting further investigation.
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