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LDL After ACS: Is Lower Better?

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, suggests 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 benefit 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. Since PROVE-IT, results have been published from the A to Z trial, in which 4497 high-risk ACS patients were randomized to either early, intensive simvastatin therapy (40 mg/day for 1 month, 80 mg/day thereafter) or a conservative strategy (placebo for 4 months, 20 mg/day of simvastatin thereafter). In A to Z, the intensive strategy showed only trends toward outcome benefits over the conservative strategy (Journal Watch Cardiology Oct 29 2004). Forthcoming trials that compare different doses of the same statin started at the same time will help to clarify the value of early, intensive statin therapy after an ACS event.

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology December 31, 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)