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Timothy J. Wilt, MD, MPH; Hanna E. Bloomfield, MD, MPH; Roderick MacDonald, MS; David Nelson, PhD; Indulis Rutks, BS; Michael Ho, MD; Gregory Larsen, MD; Anthony McCall, MD, PhD; Sandra Pineros, MPH; Anne Sales, PhD

Arch Intern Med. 2004;164:1427-1436.

Background  We conducted a meta-analysis of patients with coronary heart disease (CHD) to determine the effectiveness of statin therapy; whether effectiveness varied according to patient characteristics, outcomes, or pretreatment low-density lipoprotein cholesterol (LDL-C) levels; and the optimal LDL-C goal and the level at which to initiate statin therapy.

Methods  Randomized trials or systematic reviews for secondary prevention of CHD with statin therapy published between January 1966 and December 2002 were identified through MEDLINE and the Cochrane Library. Studies were included if they randomly assigned adults with CHD to statin therapy or control, enrolled at least 100 individuals per arm, reported clinical outcomes and LDL-C levels, and were published as full studies in English. Two reviewers abstracted data using a prospectively designed protocol.

Results  Twenty-five studies enrolling 69 511 individuals were included. Participants in 19 placebo-controlled trials had a mean age of 63 years and a mean pretreatment LDL-C level of 149 mg/dL (3.85 mmol/L); 23% were women. Statin therapy reduced CHD mortality or nonfatal myocardial infarction 25% (relative risk [RR], 0.75; 95% confidence interval [CI], 0.71-0.79), all-cause mortality 16% (RR, 0.84; 95% CI, 0.79-0.89), and CHD mortality 23% (RR, 0.77; 95% CI, 0.71-0.83). Beneficial effects were seen in women and the elderly. There were no data to determine whether lowering the LDL-C level to less than 100 mg/dL (<2.59 mmol/L) was superior to lowering it to 100 to 130 mg/dL (2.59-3.36 mmol/L). Meta-regression analyses revealed risk reductions for CHD mortality or nonfatal myocardial infarction and major vascular events across available pretreatment LDL-C levels.

Conclusion  Statin therapy reduces mortality and morbidity in adults with CHD, even at pretreatment LDL-C levels as low as 100 mg/dL (2.59 mmol/L).

From the Center for Chronic Disease Outcomes Research, Minneapolis VA Medical Center, Minneapolis, Minn (Drs Wilt, Bloomfield, and Nelson and Messrs MacDonald and Rutks); Cardiology and Health Services Research, Denver VA Medical Center, Denver, Colo (Dr Ho); Department of Cardiology, Portland VA Medical Center, Portland, Ore (Dr Larsen); Department of Internal Medicine, University of Virginia Health System, Charlottesville (Dr McCall); and Ischemic Heart Disease Quality Enhancement Research Initiative, VA Puget Sound Health Care System, Seattle, Wash (Ms Pineros and Dr Sales). The authors have no relevant financial interest in this article.

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