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Effects of Lovastatin and Pravastatin on Coronary Artery Disease
- Howard N. Hodis, MD;
- Linda Cashin-Hemphill, MD; and
- Wendy J. Mack, PhD
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IN RESPONSE:
We thank Dr. Goldstein for his careful review of our work and for bringing attention to several important issues.
However, we do not agree that patients in the MARS trial [1] and the Pravastatin Multinational Study trial [2] were “comparable”. These studies report results in two distinctly different populations. Compared with patients in the MARS trial, those in the Pravastatin Multinational Study had greater low-density lipoprotein (LDL) cholesterol levels (181 compared with 157 mg/dL) and a lower mean age. The latter study also included more women, more patients with hypertension (uncontrolled hypertension was an exclusion criterion in the MARS trial), a greater number of current cigarette smokers, and fewer persons with a previous myocardial infarction. The only similar factor, angina pectoris, was significantly greater in patients receiving placebo in the Pravastatin Multinational Study. The only angiographic trials to show significant event reduction with lipid-lowering therapies enrolled patients with higher baseline LDL cholesterol levels (180 mg/dL in the Program on the Surgical Control of Hyperlipidemic Study [POSCH], 190 mg/dL in the Familial Atherosclerosis Treatment Study (FATS), and 190 mg/dL in the St. Thomas' Atherosclerosis Regression Study (STARS).
Selection criteria for the two studies differed. The MARS trial used angiographically defined coronary artery disease criteria and excluded patients with left-main disease and those requiring coronary artery bypass surgery [1]. Patients in the Pravastatin Multinational Study were selected for an elevated cholesterol level and two additional coronary disease risk factors. Therefore, underlying status of the coronary arteries, including the extent and severity of disease, was probably dissimilar in these two patient groups. The Pravastatin Multinational Study, designed for efficacy and safety, included a mixed population of patients with and without coronary disease. It is therefore not valid to compare events between these two studies.
Further, we do not agree with Dr. Goldstein that no favorable effect on events was seen in the MARS trial. Consistent with other coronary angiographic trials, this study showed a 29% (P = 0.22) reduction in coronary events with a decrease in LDL cholesterol levels over a 2-year period [1]. Because neither MARS nor the Pravastatin Multinational Study was designed to show a reduction in events, caution should be exercised until large-scale trials designed to do so are completed. We have shown highly significant reductions in coronary events in long-term follow-up of the Cholesterol Lowering Atherosclerosis Study, which examined a cohort similar to that of the MARS trial [3]. Therefore, long-term follow-up of coronary angiographic trials is indicated as an alternative to large-scale trials.
We agree with Dr. Goldstein that different agents may differentially affect end points and clinical events. We have shown that after LDL cholesterol is reduced, other factors (such as triglyceride-rich lipoproteins) assume control of atherogenesis [4, 5]. Therefore, it is not unreasonable to assume that agents that beneficially affect other atherogenic factors may lead to further reduction of coronary artery disease progression as well as coronary events.
Howard N. Hodis, MD
Linda Cashin-Hemphill, MD
Wendy J. Mack, PhD
University of Southern California School of Medicine; Los Angeles, CA 90033
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
