LETTER TO THE EDITOR
Reply
Frank M. Sacks, MD*
* Harvard School of Public Health, Department of Nutrition, 665 Huntington Ave., Boston, Massachusetts, USA
fsacks{at}hsph.harvard.edu
I thank Dr. Davidson for clarifying some of the estimates for low density lipoprotein (LDL) reduction that I computed for statin and ezetimibe doses (1). Although we do have treatment goals for LDL cholesterol (LDL-C), it is worth emphasizing that it is risk reduction that is the ultimate goal. The additional risk reduction expected from two doublings of a statin dose or from ezetimibe remains modest in typical patients, about 15% for a patient with a pretreatment LDL-C of 190 mg/dl, and 12% when the pretreatment LDL-C is 140 mg/dl. This reflects the modest efficacy of ezetimibe, a 14% lowering of LDL-C shown in Dr. Davidson’s excellent study (2), and of two doublings of statin doses. This magnitude is consistent with much of the literature on the drug. The added value in terms of risk reduction appears rather modest and needs to be balanced against the cost, lack of long-term outcome data, and need for other medications, particularly in older patients.
My perspective is that the benefits and safety of statin therapy are very well established, and I favor its use across the approved dose ranges. I am finding ezetimibe useful in combination with 40 mg or 80 mg of a statin in patients with moderate to severe hypercholesterolemia for whom more substantial risk reduction should occur from additional LDL reduction. I am much less convinced that adverse effects of statin therapy truly occur in more than a very few patients. I base this on results of trials that compare adverse effects reported during statin therapy with those during placebo treatment in tens of thousands of patients (3,4). Myalgia is a common feature of the human condition, inexorably increasing with aging. When patients complain of myalgias while taking statins, it is important to ensure that it fits the clinical features of statin-myopathy, following the accepted guidelines for this diagnosis (5). Whether ezetimibe or other nonstatin LDL-lowering drugs like colesevelam offer a useful alternative in "statin intolerant" patients remains to be determined.
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1. Sacks FM. Low-density lipoprotein lowering therapy: an analysis of the options. J Am Coll Cardiol. 2002;40:2135–2138[Free Full Text]
2. Davidson MH, McGarry T, Bettis R, et al. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. J Am Coll Cardiol. 2002;40:2125–2134[Abstract/Free Full Text]
3. Pfeffer MA, Keech A, Sacks FM, et al. Safety and tolerability of pravastatin in long-term clinical trials. Prospective Pravastatin Pooling (PPP) Project. Circulation. 2002;105:2341–2346[Abstract/Free Full Text]
4. Heart Protection Study Collaborative Group. MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20,356 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7–22[CrossRef][Medline]
5. Pasternak RC, Smith SC Jr, Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant C. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. J Am Coll Cardiol. 2002;40:568–573
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