Letter by Brewster and van Montfrans Regarding Article, “Risks Associated With Statin Therapy: A Systematic Overview of Randomized Clinical Trials”
To the Editor:
Kashani et al1 report that in randomized trials, statin therapy (with the exclusion of cerivastatin) did not result in significant absolute increases in myalgias (risk difference per 1000 patients, 2.7 (95% CI, −3.2 to 8.7), or mild creatine kinase (CK) elevations 0.2 (95% CI, −0.6 to 0.9). The authors used data from published trials to reach this conclusion.
However, Kashani et al did not take into account that many statin trials disclose that eligible patients with muscle complaints, previous adverse responses to cholesterol-lowering therapy, or even a mild asymptomatic elevation of CK (>1.5 to 6.0 times the upper limit of normal) are not randomized.2–5
On the basis of the complete exclusion criteria, up to 76% of the screened participants in statin trials are not randomized and excluded.2–5 Thus, the incidence of hyperCKemia with the use of statins that emerges from these trials may mainly concern subjects in the lower part of the CK distribution, with a low a priori risk to develop highly elevated CK levels.
The exclusion of these patients before randomization may lead to biased reports on the frequency of occurrence of side effects with statin use. This should be acknowledged to be a limitation when adverse effects associated with statins are assessed in published trials.
Kashani A, Phillips CO, Foody JM, Wang Y, Mangalmurti S, Ko DT, Krumholz HM. Risks associated with statin therapy: a systematic overview of randomized clinical trials. Circulation. 2006; 114: 2788–2797.
LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, Gotto AM, Greten H, Kastelein JJ, Shepherd J, Wenger NK; Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005; 352: 1425–1435.
Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, Ford I, Gaw A, Hyland M, Jukema JW, Kamper AM, Macfarlane PW, Meinders AE, Norrie J, Packard CJ, Perry IJ, Stott DJ, Sweeney BJ, Twomey C, Westendorp RG; PROSPER Study Group. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002; 360: 1623–1630.