Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Lowering LDL cholesterol levels reduced fatal coronary events in patients with acute MI and average cholesterol levels

ACP J Club. 1997 Mar-Apr;126:29. doi:10.7326/ACPJC-1997-126-2-029


Source Citation

Sacks FM, Pfeffer MA, Moye LA, et al., for the Cholesterol and Recurrent Events Trial Investigators. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996 Oct 3;335:1001-9.


Abstract

Objective

To evaluate the effectiveness of lowering low-density lipoprotein (LDL) cholesterol levels in preventing coronary events after myocardial infarction (MI) in patients with average cholesterol levels.

Design

Randomized, double-blind, placebo-controlled trial with a median 5-year follow-up.

Setting

13 centers in Canada and 67 centers in the United States.

Patients

4159 patients between the ages of 21 and 75 years (mean age 59 y, 86% men) who had had an acute MI within the past 3 to 20 months; had plasma total cholesterol levels < 6.20 mmol/L, LDL cholesterol levels between 2.97 and 4.50 mmol/L, fasting triglyceride levels < 4.0 mmol/L, fasting glucose levels ≤ 12.2 mmol/L, and left ventricular ejection fractions ≥ 25%; and had no symptomatic congestive heart failure.

Intervention

2081 patients were allocated to pravastatin, 40 mg/d, and 2078 patients to matching placebo.

Main outcome measures

Fatal coronary events or nonfatal MI.

Main results

During follow-up, the LDL cholesterol level was 28% lower in the pravastatin group than in the placebo group (P < 0.001). 212 patients (10%) in the pravastatin group died of coronary heart disease (CHD) or had a nonfatal MI compared with 274 patients (13%) in the placebo group (P = 0.003). {This absolute risk reduction (ARR) of 3% means that 34 patients would need to be treated (NNT) with pravastatin (compared with placebo) to prevent 1 additional death from CHD or nonfatal MI, 95% CI 20 to 95; the relative risk reduction (RRR) was 23%, CI 9% to 35%.}* 294 patients (14%) in the pravastatin group had coronary artery bypass grafting or angioplasty compared with 391patients (19%) in the placebo group (P < 0.001). Also, patients in the pravastatin group had a lower incidence of stroke than did patients in the placebo group (2.6% vs 3.8%, P = 0.03) {ARR 1.2%; NNT 87, CI 44 to 1059; RRR 31%, CI 3% to 51%}.* No differences existed between the treatment groups for death from noncardiovascular causes. The effect of pravastatin was greater in women than in men (P = 0.05) and in patients with higher pretreatment LDL cholesterol levels (P = 0.03).

Conclusion

Lowering LDL cholesterol levels with pravastatin reduced the incidence of fatal coronary events and nonfatal MI in patients with acute MI and average cholesterol levels.

Source of funding: Bristol-Myers Squibb Pharmaceutical Research Institute.

For article reprint: Dr. F.M. Sacks, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. FAX 617-735-0299.

*Numbers calculated from data in article.


Commentary

Most patients who have had an MI would benefit from taking a β-blocker, an aspirin, and a statin. The magnitude of the average benefit is almost the same for all 3 interventions, although the costs are different.

The study by Sacks and colleagues was exemplary: the follow-up rate was almost 100%, minimal crossover occurred (< 8%), and > 86% of patients were still adhering to therapy after 5 years. These study results, in combination with the findings from the Scandinavian Simvastatin Survival Study (4S) Group (1), establish the benefit and safety of lowering cholesterol levels for patients who have had an MI and have a baseline LDL cholesterol level > 3.23 mmol/L (125 mg/dL). These patients represent about three quarters of all patients with MI. However, patients with more normal cholesterol values do not have the 2% to 3% reduction in vascular events for every 1% reduction in cholesterol levels, as is seen in patients with high cholesterol levels. In fact, the treatment benefit tapers off to zero as the baseline LDL cholesterol level nears 3.23 mmol/L (125 mg/dL).

These results might support the recommendation by the National Cholesterol Education Program (NCEP) expert panel (2) to aggressively lower "average" cholesterol values in patients with known coronary artery disease, but they do not support the recommendation to use an LDL cholesterol level > 2.6 mmol/L (100 mg/dL) as the cutpoint for initiating drug therapy. Based on this study, the cutpoint for treatment should probably be raised to 3.23 mmol/L (125 mg/dL). The recommended goal of drug therapy (an LDL cholesterol level < 2.6 mmol/L [100 mg/dL]) for patients who have had an MI may also need revision.

The benefits of statins might be established, but cost is still a major concern. For drug costs of U.S. $500 000 (to treat 100 people with MI and an LDL cholesterol level between 3.23 and 3.88 mmol/L [125 to 150 mg/dL] with 40 mg/d of pravastatin for 5 years), one might expect to help 5 to 10 patients by preventing 1 to 2 deaths, 2 to 10 nonfatal MIs, 1 to 3 strokes, and 4 to 6 angioplasties or bypass surgeries.

Arthur T. Evans, MD, MPH
University of North Carolina at Chapel HillChapel Hill, North Carolina, USA


References

1. Scandinavian Simvastatin Survival Study Group. Lancet. 1994;344:1383-9.

2. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 1993;269:3015-23.