Effect of Statins on All-Cause Mortality in Adults: A Systematic Review and Meta-Analysis of Propensity Score-Matched Studies

Abstract

Statins are lipid-lowering medications used for the prevention of cardiovascular disease (CVD), but the pleiotropic effects of statins might be beneficial in other chronic diseases. This meta-analysis investigated the association between statin use and mortality in different chronic conditions. Eligible studies were real-world studies that compared all-cause mortality over at least 12 months between propensity score-matched statin users and non-users. Overall, 54 studies were included: 21 in CVD, 6 in chronic kidney disease, 6 in chronic inflammatory diseases, 3 in cancer, and 18 in other diseases. The risk of all-cause mortality was significantly reduced in statin users (hazard ratio: 0.72, 95% confidence interval: 0.66–0.76). The reduction in mortality risk was similar in CVD studies (0.73, 0.66–0.76) and non-CVD studies (0.70, 0.67–0.79). There were no significant differences in the risk reduction between cohorts with different diseases (p = 0.179). The greatest mortality reduction was seen in studies from Asia (0.61, 0.61–0.73) and the lowest in studies from North America (0.78, 0.73–0.83) and Australia (0.78, 0.62–0.97). There was a significant heterogeneity (I2 = 95%, tau2 = 0.029, p < 0.01). In conclusion, statin use was associated with a significantly reduced risk of all-cause mortality in real-world cohorts with CVD and non-CVD.

Long-Term Mortality Prediction with Pooled Cohort Equations: Implications for Lipid-Lowering Therapy

“…Statins have been widely used as the primary lipid-lowering drugs. Several clinical trials and metaanalysis have demonstrated their beneficial effects on all-cause mortality and cardiovascular mortality in individuals with or without cardiovascular disease 11,[13][14][15]17,[21][22][23] . Consistent with this, we found that lipid-lowering therapy was significantly associated with a 30% reduction in allcause mortality and a 35% reduction in cardiovascular mortality in matched individuals with comparable 10-year risk of ASCVD.…”

Application of a novel index for understanding vascular health following pharmacological intervention in a pre-clinical model of metabolic disease

“…These results suggest that multiple treatments may be required for realizing optimal outcomes, or that the benefits derived from pharmacological agents with pleiotropic effects such as atorvastatin ( Frisbee et al, 2018 ), and to some extent anti-hypertensive agents ( Frisbee et al, 2018 ), may allow for a greater maintenance of vascular health beyond that which would be expected from simple risk factor reduction alone. Recent study involving machine learning approaches have suggested these outcomes may be realized in chronic metabolic disease, where chronic interventions with pharmacological agents with beneficial impacts in addition to risk factor reduction were highly effective at improving functional outcomes that may not have been associated with the intended use of the drug ( Nowak et al, 2022 ).…”

Pharmacological Utility of PPAR Modulation for Angiogenesis in Cardiovascular Disease

“…They lower cholesterol through inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-reductase [117]. Statin use is associated with a significantly reduced risk of all-cause mortality in cohorts with cardiovascular and noncardiovascular disease, including cancer [118]. Not only antiatherogenic and anti-inflammatory actions of statins have been associated with the activation of PPARα and γ ( [119][120][121][122], but also cardioprotective statin effects, such as the inhibition of cardiac hypertrophy and fibrosis, can be attributed to PPARα and γ modulation [123][124][125].…”