LETTER
Hypolipidemic Drugs in Coronary Artery Disease
William L. Isley, MD
1 June 1997 | Volume 126 Issue 11 | Page 916
TO THE EDITOR:
Pasternak and colleagues [1] address the important question of the need for combination therapy in patients with coronary heart disease and "normal" cholesterol values. However, they imply in their introduction and discussion that the amount of low-density lipoprotein (LDL) cholesterol lowering achieved is similar for all currently approved 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins). Specifically, the authors ignore the well-known dose-response curves of these agents, as shown in two studies they cite in their article. The EXCEL (Expanded Clinical Evaluation of Lovastatin) study [2] clearly shows that lovastatin has an increasing effect as doses are increased from 20 mg daily (mean LDL cholesterol lowering, 24%) to 80 mg daily (mean LDL cholesterol lowering, 40%). Similarly, Stein and colleagues [3] showed mean LDL cholesterol lowering of 32% with a simvastatin dosage of 20 mg/d and of 40% with a dosage of 40 mg/d. (Pasternak and colleagues incorrectly give the results for cholestyramine alone as the results for resin plus simvastatin therapy.) The authors would probably have seen less need for combination therapy if they had used another statin at a dosage that would have achieved more LDL cholesterol lowering.
Of more significance is the unanswered question of whether combination therapy with agents that have complementary roles (such as statins, which primarily affect LDL cholesterol levels, and niacin, which primarily affects very low density lipoprotein and high-density lipoprotein cholesterol [HDL] levels) has any advantage for clinical end points over monotherapy, which primarily targets LDL cholesterol concentrations (as mandated by the National Cholesterol Education Program [4]). The Scandinavian Simvastatin Survival Study (4S) [5] seems to indicate that, at least in patients with moderate hypercholesterolemia, marked LDL cholesterol reduction (mean decrease of 35% over 5.4 years) accompanied by a modest increase in HDL cholesterol levels and decrease in triglyceride levels has significant benefits with regard to coronary events, coronary mortality, and all-cause mortality. It is possible that patients whose LDL cholesterol level is less severely elevated may require different lipid intervention strategies to achieve a similar outcome.
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Author and Article Information
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University of Missouri-Kansas City, Kansas City, MO
1. Pasternak RC, Brown LE, Stone PH, Silverman DI, Gibson CM, Sacks FM. Effect of combination therapy with lipid-reducing drugs in patients with coronary heart disease and "normal" cholesterol levels. A randomized, placebo-controlled trial. The Harvard Atherosclerosis Reversibility Project (HARP) Study Group. Ann Intern Med. 1996; 125:529-40.
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. Arch Intern Med. 1991; 151:43-9.
3. Stein E, Kreisberg R, Miller V, Mantell G, Washington L, Shapiro DR, et al. Effects of simvastatin and cholestyramine in familial and nonfamilial hypercholesterolemia. Multicenter Group I. Arch Intern Med. 1990; 150:341-5.
4. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA. 1993; 269:3015-22.
5. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease. The Scandinavian Simvastatin Survival Study (4S). Lancet. 1994; 344:1383-9.
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