Published Online
on February 5, 2007

A more recent version of this article appeared on February 13, 2007

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Submitted on July 27, 2006
Accepted on November 20, 2006

Effects of Intensive Versus Moderate Lipid-Lowering Therapy on Myocardial Ischemia in Older Patients With Coronary Heart Disease. Results of the Study Assessing Goals in the Elderly (SAGE)

Prakash Deedwania MD^*, Peter H. Stone MD, C. Noel Bairey Merz MD, Juan Cosin-Aguilar MD, Nevres Koylan MD, Don Luo PhD, Pamela Ouyang MBBS, Ryszard Piotrowicz MD, Karin Schenck-Gustafsson MD, PhD, Philippe Sellier MD, James H. Stein MD, Peter L. Thompson MD, and Dan Tzivoni MD

From the UCSF School of Medicine, San Francisco, and Veterans Administration Central California Healthcare System (VACCHCS), Fresno, Calif (P.D.); the Brigham and Women’s Hospital (P.H.S.), Boston, Mass; the Cedars-Sinai Medical Center and the David Geffen School of Medicine at UCLA (C.N.B.M.), Los Angeles, Calif; the Hospital La Fe. Centro de Investigacion (J.C.-A.), Valencia, Spain; the Istanbul University (N.K.), Istanbul Faculty of Medicine, Istanbul, Turkey; Pfizer Inc. (D.L.), New York, NY; the Johns Hopkins Bayview Medical Center (P.O.), Johns Hopkins University, Baltimore, Md; the Instytut Kardiologii (R.P.), Warsaw, Poland; the Karolinska University Hospital (K.S.-G.), Stockholm, Sweden; the Hôpital Broussais-HEGP (P.S.), AP-HP Paris, France; the University of Wisconsin Medical School (J.H.S.), Madison, Wis; the University of Western Australia and Sir Charles Gairdner Hospital (P.L.T.), Perth, Australia; and the Shaare Zedek Medical Center (D.T.), Jerusalem, Israel.

^* To whom correspondence should be addressed. E-mail: deed{at}fresno.ucsf.edu.

Background--Clinical trials have demonstrated that, compared with placebo, intensive statin therapy reduces ischemia in patients with acute coronary syndromes and in patients with stable coronary artery disease. However, no studies to date have assessed intensive versus moderate statin therapy in older patients with stable coronary syndromes.

Methods and Results--A total of 893 ambulatory coronary artery disease patients (30% women) 65 to 85 years of age with 1 episode of myocardial ischemia that lasted 3 minutes during 48-hour ambulatory ECG at screening were randomized to atorvastatin 80 mg/d or pravastatin 40 mg/d and followed up for 12 months. The primary efficacy parameter (absolute change from baseline in total duration of ischemia at month 12) was significantly reduced in both groups at month 3 and month 12 (both P<0.001 for each treatment group) with no significant difference between the treatment groups. Atorvastatin-treated patients experienced greater low-density lipoprotein cholesterol reductions than did pravastatin-treated patients, a trend toward fewer major acute cardiovascular events (hazard ratio, 0.71; 95% confidence interval, 0.46, 1.09; P=0.114), and a significantly greater reduction in all-cause death (hazard ratio, 0.33; 95% confidence interval, 0.13, 0.83; P=0.014).

Conclusions--Compared with moderate pravastatin therapy, intensive atorvastatin therapy was associated with reductions in cholesterol, major acute cardiovascular events, and death in addition to the reductions in ischemia observed with both therapies. The contrast between the therapies’ differing efficacy for major acute cardiovascular events and death and their nonsignificant difference in efficacy for reduction of ischemia suggests that low-density lipoprotein cholesterol-lowering thresholds for ischemia and major acute cardiovascular events may differ. The Study Assessing Goals in the Elderly (SAGE) demonstrates that older men and women with coronary artery disease benefit from intensive statin therapy.

Key words: atherosclerosis • electrocardiography • hypercholesterolemia • ischemia • statins

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