Editor's Message  |   July 2003
Editor's Message
Author Notes
  • Dr Butler is director of medical education at St John Oakland Hospital in Madison Heights, Mich, and an associate professor of medicine at Michigan State University–College of Osteopathic Medicine in East Lansing. 
Article Information
Cardiovascular Disorders / Preventive Medicine
Editor's Message   |   July 2003
Editor's Message
The Journal of the American Osteopathic Association, July 2003, Vol. 103, Cov2. doi:
The Journal of the American Osteopathic Association, July 2003, Vol. 103, Cov2. doi:
With numerous trials completed to date evaluating the role of statin therapy in the reduction of cardiovascular risk, one might ask what else physicians need to know about treatment with these drugs. Although most trials have generally identified fairly large relative risk reductions associated with active lipid-lowering therapy, careful review of these studies reveals that much is left to be learned and many questions remain—questions that may have a direct impact on physicians' ability to provide high-quality, safe, and cost-effective care to their patients. 
Perhaps foremost is the need to determine the mechanisms by which statins confer benefit to patients. On the surface, this should seem obvious. As potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA), statins consistently lower low-density lipoprotein cholesterol (LDL-C) concentrations. Failure to lower LDL-C concentrations has resulted in no apparent benefit from therapy.1 
Clear correlations, however, do not always exist between the magnitude of change in LDL-C levels and the degree of cardiovascular risk reduction associated with statin therapy.2 In addition, some investigators have failed to identify a relationship between baseline levels of LDL-C and the magnitude of treatment benefit.1-4 Furthermore, in a recent post hoc analysis of one primary prevention trial, subjects randomly assigned to treatment with pravastatin sodium were found to have had greater reductions in cardiovascular event rates than were predicted by post-treatment LDL-C levels and the Framingham risk equation.1 
These observations require explanations beyond LDL-C reduction to understand the full benefit of statin therapy. It is becoming clear that statins have pleotrophic effects, influencing many aspects of atherosclerotic plaque development and stabilization.5 
These observations have led to an expansion of our current models of risk assessment to include new and emerging risk factors. 
It is also increasingly important for clinicians to understand that although statin therapy has consistently been shown to result in significant relative reductions in cardiovascular risk, absolute benefits have not always been robust. A clear example can be seen in the recently published Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA) trial.3 The ASCOT-LLA performed a second randomization to either atorvastatin calcium or placebo in 10,305 hypercholesterolemic subjects who were previously enrolled into one of two arms of antihypertensive therapy within the larger ASCOT.6 Although the cholesterol reduction arm of the trial was terminated early because of a highly significant 36% relative risk reduction in the atorvastatin-treated group, statin treatment resulted in only a small absolute increase of 95% to 97% in the probability of remaining free from a myocardial infarction for 5 years.7 Another expression of the absolute benefit would be to say that approximately 90 patients with well-controlled hypertension would need to be treated with atorvastatin for 3.3 years to prevent one additional nonfatal or fatal myocardial infarction. Patients, physicians, and society will need to determine if treatment effects of this magnitude are worth the effort. 
This supplement of the JAOA includes articles derived from a series of presentations made during the 2002 American Osteopathic Association satellite symposium Clinical Pathways: The Role of Statins in the Treatment of Dyslipidemia. In the first article, Larry L. Carr, DO, of Bay Medical Center in Bay City, Mich, provides an overview of the symposium. The second article, by Michael B. Clearfield, DO, of the University of North Texas Health Science Center at Fort Worth—Texas College of Osteopathic Medicine, provides a thorough review and interpretation of the key lipid-lowering trials done to date, reviews the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III, ATP III),8 and discusses the emerging role of inflammatory markers in assessment of cardiovascular risk. Robert J. Chilton, DO, of the University of North Texas Health Science Center at San Antonio, provides the final article, which directs the reader to the developing body of evidence supporting the nonlipid-lowering benefits of statin therapy. 
Clinicians who spend time in careful review of these articles by leading authors in the osteopathic medical profession will be well rewarded. 
West of Scotland Coronary Prevention Study Group. Influence of pravastatin and plasma lipids on clinical events in the West of Scotland Coronary Prevention Study (WOSCOPS). Circulation. .(1998). ;97:1440-1445.
Heart Protection Study Collaborative Group. MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomized placebo-controlled trial. Lancet. . 2002;360:7-22.
Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, et al, for the ASCOT Investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. .(2003). ;361:1149-1158.
ALLHAT Collaborative Research Group. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomised to pravastatin vs usual care. JAMA. .(2002). ;288:2998-3007.
Forrester JS. Prevention of plaque rupture: a new paradigm of therapy. Ann Intern Med. .(2002). ;137:823-833.
Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, et al. Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. J Hypertens. . 2001;6:1139-1147.
Lindholm LH, Samuelsson O. What are the odds at ASCOT today? Lancet. . 2003;361:1144-1145.
Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. . 2001;285:2486-2497.