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LDL After ACS: Is Lower Better?

For acute coronary syndrome patients in the PROVE-IT trial, the answer was yes.

Current guidelines recommend a target LDL-cholesterol level of less than 100 mg/dL for patients with coronary artery disease. In a multicenter, international, randomized trial, supported by the maker of pravastatin, researchers compared two LDL-lowering strategies: a 100-mg/dL target with 40 mg/day of pravastatin and a 70-mg/dL target with 80 mg/day of atorvastatin. Subjects were 4162 acute coronary syndrome (ACS) patients (mean age, 58; 22% women) with total-cholesterol levels of 240 mg/dL or lower.

Median LDL levels in both groups were 106 mg/dL at randomization (about a week after the ACS event). During 2 years of follow-up, levels declined to 95 mg/dL with standard-dose pravastatin and to 62 mg/dL with high-dose atorvastatin.

Two-year incidence of the primary endpoint -- death, MI, rehospitalization for documented unstable angina, revascularization 30 days postrandomization, or stroke -- was significantly lower with atorvastatin (22.4%) than with pravastatin (26.3%). A similar difference was found for the incidence of MI, revascularization , or death from coronary heart disease (19.7% vs. 22.3%). Compared with pravastatin recipients, atorvastatin recipients had significantly lower rates of revascularization (14% lower), recurrent unstable angina (29% lower), and all-cause mortality (28% lower). Patients younger than 65 and those with baseline LDL 125 mg/dL showed the greatest benefits with atorvastatin. Alanine aminotransferase (ALT) elevations were significantly more common with high-dose atorvastatin (3.3%) than with low-dose pravastatin (1.1%). Drug-discontinuation rates were similar in the two groups.

Comment: This study, known as PROVE-IT, provides convincing evidence that aggressive statin treatment after an ACS event yields better outcomes than standard treatment does. For every 25 ACS patients who received high-dose atorvastatin, one primary-endpoint event was avoided. This is a dramatic benefit that offsets the slightly higher rate of ALT elevation with the more intensive therapy. A point worth emphasizing is that moderate therapy with one drug (pravastatin) was tested against intensive therapy with another (atorvastatin); the study design would have been stronger if a moderate level of atorvastatin therapy also had been tested. Nevertheless, the findings should influence practice for patients who would have been eligible for the study.

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology April 16, 2004

Citation(s):

Cannon CP et al. for the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004 Apr 8; 350:1495-504.

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• Medline abstract (Free)

Topol EJ. Intensive statin therapy -- A sea change in cardiovascular prevention. N Engl J Med 2004 Apr 8; 350:1562-4.

• Original article (Subscription may be required)
• Medline abstract (Free)