The CARE trial: Statins in coronary artery disease [Classics Series]

Classics Series, Landmark Trials in Medicine

1. Statin therapy reduces the risk of coronary events in patients with known coronary heart disease and low-density lipoprotein levels >125 mg/dL.

2. The reduction in coronary events with statin therapy was found to be greater in women and patients with higher pretreatment LDL levels.

Original Date of Publication: October 1996

Study Rundown: Serum cholesterol levels have long been considered important risk factors for the development of coronary heart disease, and previous studies have demonstrated that lowering cholesterol levels in patients with high cholesterol significantly reduces the risk of coronary events. The Cholesterol and Recurrent Events (CARE) trial examined the effect of lowering low-density lipoprotein (LDL) levels on the incidence of coronary events in patients with known coronary heart disease and average cholesterol levels. The study demonstrated that treating such patients with pravastatin to lower LDL levels significantly reduced the risk of the composite endpoint of fatal coronary heart disease or nonfatal myocardial infarction when compared to placebo (RR 24%; 95%CI 9-36%). This difference was driven by a reduction in the rate of nonfatal myocardial infarctions, as there was no significant difference in mortality from coronary heart disease. Notably, women and patients with higher pretreatment LDL levels experienced significantly greater risk reductions than men and patients with lower pretreatment LDL levels, respectively. In summary, this trial supports the use of statin therapy to lower cholesterol levels patients with known coronary heart disease and LDL levels >125 mg/dL.

Click to read study in NEJM

In-Depth [randomized, controlled study]: The CARE trial randomized 4,159 patients from 80 centres across Canada and the United States. Patients were eligible if they had an acute myocardial infarction 3-20 months prior to randomization, were between 21-75 years of age, had total cholesterol levels of <240 mg/dL, had LDL cholesterol levels between 115-174 mg/dL, had fasting triglyceride levels <350 mg/dL, had fasting glucose levels <220 mg/dL (12.2 mmol/L), had left ventricular ejection fractions of ≥25%, and did not have symptomatic congestive heart failure. Patients were randomized to receive pravastatin 40 mg daily or placebo, and were followed for a median of 5.0 years. The primary endpoint was a composite of fatal coronary heart disease or nonfatal myocardial infarction.

Patients being treated with pravastatin experienced significantly lower rates of the primary endpoint as compared with patients taking placebo (RR 24%; 95%CI 9-36%). This difference was driven by a significant reduction in nonfatal myocardial infarctions (RR 23%; 95%CI 4-39%), as there was no significant difference in death from coronary heart disease. Moreover, the risk of revascularization (i.e., coronary artery bypass graft, percutaneous transluminal coronary angioplasty) was significantly lower in patients taking pravastatin (RR 27%; 95%CI 15-37%). Women experienced significantly larger reductions in the risk of coronary events as compared with men (p=0.05 for interaction between sex and outcomes). Of note, results differed according to pretreatment LDL levels. Patients with LDL >150 mg/dL experienced a larger risk reduction compared to those with LDL between 125-150 mg/dL at baseline (35% vs. 26%, p=0.03 for interaction between pretreatment LDL and risk reduction).

Image: PD

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