REPLY
Injury, Death, and Cholesterol
Peter Cummings, MD, MPH, and
Bruce M. Psaty, MD, PhD
1 November 1994 | Volume 121 Issue 9 | Pages 719-720
IN RESPONSE:
Our meta-analysis of primary prevention trials of cholesterol-lowering interventions in men showed the relative risk for death from injury among treated men compared with that of controls to be 1.42 (95% CI, 0.94 to 2.15) [1]. Although Dr. Muldoon disagrees with our inclusion of the EXCEL trial [2] and exclusion of the Veterans Affairs trial [3], these choices are of little practical importance. Including the Veterans Affairs trial and excluding the EXCEL trial produces essentially the same estimate of effect, as reported in the second line of Dr. Muldoon's Table 1; that is, our findings are substantially in agreement with those of Dr. Muldoon.
Dr. Muldoon seems to agree that the best data from the WHO clofibrate trial are those reported from the intention-to-treat analysis [4]. When Muldoon and colleagues [5] published their meta-analysis in 1990, the intention-to-treat results were not available. It is not clear why he continues to use the older WHO data in some of the calculations. We believe that the results most free of bias are based on intention-to-treat analyses.
We share Dr. Muldoon's concern about the possible adverse effects of cholesterol-lowering therapy and state in our review [1] that his meta-analysis [5] helped to focus attention on this topic. Although we found a slightly smaller estimate of effect (and a wider confidence interval) than he did, we concluded that cholesterol-lowering interventions in primary prevention trials are associated with an increase in the risk for death from injury among men. We are not certain whether this association is due to chance or to an adverse effect of cholesterol-lowering therapy. The results of several large trials of cholesterol-lowering interventions will be presented before the turn of the century, and, if deaths from injury are adequately reported, this question may soon be clarified.
1. Cummings P, Psaty BM. The association between cholesterol and death from injury. Ann Intern Med. 1994; 120:848-55.
2. Bradford RH, Shear CL, Chremos AN, Dujovne C, Downton M, Franklin FA, et al. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia. Ann Intern Med. 1993; 118:850-5.
3. Dayton S, Pearce ML, Hashimoto S, Dixon WJ, Tomiyasu U. A controlled clinical trial of a diet high in unsaturated fat in preventing complications of atherosclerosis. Circulation. 1969; 39-40(Suppl II):1-63.
4. Heady JA, Morris JN, Oliver MF. WHO clofibrate/cholesterol trial: clarifications (Letter). Lancet. 1992; 340:1405-6.
5. Muldoon MF, Manuck SM, Matthews KM. Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials. BMJ. 1990; 301:309-14.
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