statin use

Modest Reduction in Cardiovascular Outcomes From Statins

The absolute reductions in individual cardiovascular outcomes from statins are modest compared with relative risk reductions, according to results of a meta-analysis of 21 randomized clinical trials (RCTs).

Composite outcomes are often used in trials evaluating the association between statin-induced reductions in low-density lipoprotein cholesterol (LDL-C) and decreases in deaths, myocardial infarctions (MIs), and strokes combined. As a result, the association between LDL-C reductions and decreases in individual outcomes such as MI is unclear. 

To determine the association between reductions in lipoprotein cholesterol (LDL-C) levels and decreases in individual cardiovascular outcomes, researchers reviewed 21 RCTs on the use of statins to prevent these cardiovascular outcomes when considered individually.

They identified these trials by searching PubMed and Embase from January 1987 to June 2021 for large RCTs with a planned duration of at least 2 years that reported absolute changes in levels of LDL-C after treatment with statins or placebo in adults. The primary outcome of the analysis was all-cause mortality, and secondary outcomes were myocardial infarctions (MIs) and stroke.

Considerable heterogeneity was found in the results of these trials. However, the analysis revealed an absolute risk reduction of 0.8% (95% CI, 0.4%-1.2%) for all-cause mortality, 1.3% (95% CI, 0.9%-1.7%)  for MI, and 0.4% (95% CI, 0.2%-0.6%) for stroke. A relative risk reduction of 9% (95% CI, 5%-14%) was observed for all-cause mortality, 29% (95% CI, 22%-34%) for MI, and 14% (95% CI, 5%-22%) for stroke in those randomized to statin treatment compared with controls. 

A meta-regression done to determine the effect of the magnitude of the LDL-C reduction on these outcomes produced inconclusive results.

“The results of this meta-analysis suggest that the absolute risk reductions of treatment with statins . . . are modest compared with the relative risk reductions, and the presence of significant heterogeneity reduces the certainty of the evidence,” researchers concluded.

Moreover, the absolute benefits of statins “may not be strongly mediated through the degree of LDL-C reduction” statins produce.


—Ellen Kurek



Byrne P, Demasi M, Jones M, et al. Evaluating the association between low-density lipoprotein cholesterol reduction and relative and absolute effect of statin treatment: a systematic review and meta-analysis. JAMA Intern Med. Published online March 14, 2022. Accessed March 21, 2022. doi:10.1001/jamainternmed.2022.0134