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4/5/2001

Early Atorvastatin Use May Cut Ischemia Risk

Kate Traynor

Early initiation of atorvastatin therapy after a myocardial infarction or episode of unstable angina may prevent new ischemic events, says a report in the April 4 Journal of the American Medical Association (JAMA) (PDF).

Patients who began taking atorvastatin before release from the hospital were 26 percent less likely than placebo users to be hospitalized for cardiac ischemia within 16 weeks after the initial event. But the likelihood of dying or of surviving a cardiac arrest or new myocardial infarction was similar in the drug and placebo groups.

Atorvastatin use did not reduce patients’ need for a cardiac revascularization procedure. The risk of stroke, a rare event in both patient groups, was halved among atorvastatin users. This positive finding, however, just passed the study's threshold for statistical significance.

Abnormal liver-function-test results were found about four times as often in patients who received the drug as in placebo users. The dosage of atorvastatin used in the study, 80 mg/day, is the highest listed in the U.S. product labeling.

The study involved 3,086 adults who were hospitalized for unstable angina or an acute myocardial infarction not characterized by electrocardiographic Q-wave abnormalities. Patients from more than 120 medical centers in the United states and 17 other countries participated in the study, called the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial.

Patients who were likely to undergo cardiac revascularization could not participate in the study. Also excluded were most patients with a total serum cholesterol level of more than 270 mg/dL and those already taking any lipid-lowering drug except for niacin, 500 mg/day.

An undetermined number of patients were screened for eligibility during their first four days in the hospital. A total of 1,548 patients were randomly assigned to take a placebo for 16 weeks, the other 1,538 took atorvastatin.

Study participants were 65 years old on average. Eighty-six percent of the patients were white, and about 35 percent were women.

Sixty-eight people in the placebo group and 64 in the atorvastatin group died during the study. A total of 130 placebo users and 95 patients in the atorvastatin group were hospitalized for symptoms of myocardial ischemia.

The combined risk of dying, surviving a myocardial infarction or cardiac arrest, or returning to the hospital because of unstable angina was lower in the atorvastatin group than in the placebo group. This finding, however, barely exceeded the threshold of significance and was only evident after five weeks of therapy.

Three patients in the placebo group and eight in the atorvastatin group could not be monitored for the full 16 weeks. Harvard Medical School clinician Frank M. Sacks, M.D., noted in an editorial (PDF) for JAMA that the statistical difference favoring atorvastatin could disappear if many of the 11 patients lost to follow-up had died or had a serious cardiac event.

Sacks also questioned the study’s use of an 80-mg daily dose of atorvastatin and said that prescribers most commonly order a dosage of 10 mg/day. An 80-mg dose, he said, is typically reserved for patients with severe hyperlipidemia.

Despite his stated misgivings about the MIRACL trial’s ability to prove that atorvastatin therapy benefited the study participants, Sacks concluded that the drug did no harm. The positive findings, he said, justify getting patients started on statin therapy while still in the hospital.

The MIRACL study was supported by a grant from Pfizer Inc., manufacturer of the Lipitor brand of atorvastatin. Sacks, the editorialist, was the principal investigator of a manufacturer-funded study assessing the lipid-lowering effects of a competing product, Bristol-Myers Squibb Co.’s pravastatin, or Pravachol.