Statin-related adverse events: A meta-analysis

doi:10.1016/j.clinthera.2006.01.005

Clinical Therapeutics

Volume 28, Issue 1, January 2006, Pages 26-35

https://doi.org/10.1016/j.clinthera.2006.01.005 Get rights and content

Abstract

Background:

The absolute frequencies of adverseevents (AEs) between statins and placebo are very low in clinical trials, making clinical interpretation and application difficult.

Objectives:

This meta-analysis was intended to synthesize the collective AE data observed in prospective randomized clinical trials to facilitate clinical interpretation.

Methods:

Using the search terms atorvastatin, simvastatin,pravastatin, rosuvastatin, fluvastatin, lovastatin, prospective trial, and randomized trial, the MEDLINE/EMBASE and the Cochrane Collaboration databases were reviewed for prospective randomized primary and secondary prevention trials of statin monotherapy. Nonrandomized uncontrolled studies and those missing AE data were excluded. The Mantel-Haenszel test for fixed and random effects was used to calculate odds ratios (ORs) and log ORs.

Results:

Eighteen trials including 71,108 persons, and 301,374 person-years of follow-up were represented in this analysis. There were 36,062 persons receiving a statin and 35,046 receiving a placebo. Statin therapy increased the risk of any AE by 39% (OR = 1.4; 95% CI, 1.09–1.80; P = 0.008; NNH [number needed to harm] = 197) compared with placebo. Statins were associated with a 26% reduction in the risk of a clinical cardiovascular event (OR = 0.74; 95% CI, 0.69–0.80; P < 0.001; number needed to treat = 27). Treating 1000 patients with a statin would prevent 37 cardiovascular events, and 5 AEs would be observed. Serious events (creatine phosphokinase >10 times the upper limit of normal or rhabdomyolysis) are infrequent (NNH = 3400) and rhabdomyolysis, although serious, is rare (NNH = 7428). Atorvastatin was associated with the greatest risk of AEs and fluvastatin with the least risk. Simvastatin, pravastatin, and lovastatin had similar odds of AEs. Nonurgent AEs such as myalgia and liver function elevations were responsible for approximately two thirds of AEs reported in trials.

Conclusions:

Statin therapy was associated withgreater odds of AEs compared with placebo but with substantial clinical benefit. Similar rates of serious AEs were observed between statin and placebo.

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Review ArticleStatin-related adverse events: A meta-analysis

Abstract

Background:

Objectives:

Methods:

Results:

Conclusions:

Lancet

Am J Cardiol

Atherosclerosis

J Am Coll Cardiol

Am J Cardiol

Lancet

Lancet

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the NationalCholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)

JAMA

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Circulation

Statin-associated myopathy

JAMA

Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: The MIRACL study: A randomized controlled trial

JAMA

Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: A prospective, randomized, double-blindtrial

Circulation

Review Article
Statin-related adverse events: A meta-analysis