Letter by Koh and Quon Regarding Article, “Evidence Mandating Earlier and More Aggressive Treatment of Hypercholesterolemia”
To the Editor:
Aggressive intervention to lower low-density lipoprotein cholesterol (LDL-C) with statins significantly reduces cardiovascular risk. Steinberg et al1 posited that the results of the 5-year statin trials seriously underestimate the ultimate potential of cholesterol-lowering therapy, and they strongly recommended more aggressive use of lipid-lowering regimens. However, the safety of statins at high dosages, particularly with respect to cancer, is controversial.2 The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study reports fewer patients with ischemic cardiovascular events but higher incidence of cancer in the simvastatin–ezetimibe treatment group, with mean age 67.7 years (mean serum LDL-C decreased from 140 to 53 mg/dL for 5 years).3 This is consistent with epidemiological studies associating low cholesterol levels with a higher incidence of cancer. Indeed, increased cancer deaths may offset lower cardiac mortality associated with reduced cholesterol.2 Statin use per se is not associated with increased risk of cancer.4 Inverse associations exist between cancer incidence and LDL-C levels (not percent or absolute LDL-C reduction).2
Achieving LDL-C targets using statins alone may not be as beneficial as attaining these levels by other means. It may be prudent to reduce LDL-C levels to ≈70 mg/dL with statins alone only in patients with very high cardiovascular risk. In light of the pleiotropic effects of statins, combination therapy may be an important consideration for a majority of patients.5
Overall mortality rates are determined by more than a single biomarker. In addition, the mechanisms by which a biomarker is altered may contribute importantly to the clinical outcome.
Steinberg D, Glass CK, Witztum JL. Evidence mandating earlier and more aggressive treatment of hypercholesterolemia. Circulation. 2008; 118: 672–677.
Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E, Gohlke-Bärwolf C, Holme I, Kesäniemi YA, Malbecq W, Nienaber CA, Ray S, Skjaerpe T, Wachtell K, Willenheimer R; SEAS Investigators. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008; 359: 1343–1356.