Risk of Statins
Risk of Statins
Abstract & Commentary
By Michael H. Crawford, MD, Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer.
Synopsis: Available statins are associated with a small increased risk of hepatotoxicity, but not muscle toxicity or drug discontinuation for adverse effects.
Source: Kashani A, et al. Risks Associated with Statin Therapy. Circulation. 2006;114:2788-2797.
Despite well-proven effectiveness, statin therapy is underutilized. This may be due to perceived risks by physicians and patients. Thus, Kashani and colleagues prepared a meta analysis of 35 randomized controlled trials of 74,102 patients using 6 statins currently on the market. Four cerivastatin trials were analyzed separately, since it is no longer on the market. Study inclusion characteristics included documented hyperlipidemia, double-blind, > 100 patients per arm, statin monotherapy vs placebo, and full documentation of adverse events.
Risk of myalgias (risk difference / 1,000 patients = 2.7, 95% CI -3.2 to 8.7) creatine kinase elevation (RD = 0.2, CI -0.6 to 0.9) rhabdomyolysis (RD 0.4, CI -0.1 to 0.9) and drug discontinuation for any adverse event (RD -0.5, CI -4.3 to 3.3) were not significantly different between statin and placebo. However, the risk of transaminase elevations was higher on statins (RD 4.2, CI 1.5 to 6.9). Liver toxicity reached statistical significance in the fluvastatin and lovastatin individual trials. Individual comparisons showed a higher incidence of muscle toxicity with rosuvastatin, but this was not significant. Cerivastatin showed a significant increase in rhabdomyolysis (RD 12.4, CI 5.4 to 19.3, p < 0.01), but not myalgias or creatine kinase elevations. The authors concluded that available statins are associated with a small increased risk of hepatotoxicity, but not muscle toxicity or drug discontinuation for adverse effects. Cerivastatin was the only agent that showed an increase in rhabdomyolysis and it has been withdrawn from the market.
Commentary
This study is of particular interest to me because I have found considerable patient resistance to statin therapy. Maybe this is just another "California values" issue, but I suspect many have had the same problem. The internet must be full of horror stories about statins, and my patients tell me that their herbal medicine retailers rail against them in favor of the "natural" compounds they sell. Thus, this article is very reassuring and I can counter my reluctant patients with data in over 74,000 statin users. The muscle toxicity issue is really put to rest by this study; the available statins just don't significantly affect the muscles. Also, as they point out, rhabdomyolysis is rare and usually associated with drug-to-drug interactions. It was reassuring to see that cerivastatin did significantly increase rhabdomyolysis; justifying its withdrawal from the market. Transaminitis was increased to about 4/1,000 patients treated with statins, but this is most often asymptomatic and reversible. Liver failure is rare, if present. Therefore, this analysis supports the conclusion of the ACC / AHA / NHLBI guidelines that screening liver enzymes and creatine kinase only be performed if patients have symptoms.
There are some limitations to the study. Clinical trial populations are usually younger and healthier than the average patient populations. How the latter are affected by statins is unknown. There is limited data on rosuvastatin since it is relatively new. There is little data on drug-to-drug interactions such as statins and fibrates. Reports of statins causing memory loss and other neurologic symptoms could not be analyzed because of insufficient data. Finally, relative risk of adverse effects at different doses could not be evaluated. This is an important point because many believe from experience that adverse effects are more common with higher doses and often abate with dose reductions, without having to stop the statin completely. More data on this observation would be useful. In the final analysis, this study confirms the safety of these highly effective agents.
Available statins are associated with a small increased risk of hepatotoxicity, but not muscle toxicity or drug discontinuation for adverse effects.Subscribe Now for Access
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