1. Home>
2. Specialties>
3. General Medicine>
4. Summary and Comment

Are Lower LDL Targets Beneficial in Patients with Stable CHD?

Aggressive LDL lowering appears to provide cardiovascular benefit, but in this study it was also associated with higher noncardiovascular mortality.

In light of data from several recent trials, the National Cholesterol Education Panel (NCEP) recently added an optional LDL goal of <70 mg/dL in patients at "very high risk," such as those with acute coronary syndromes, and those with established cardiovascular disease plus multiple major or poorly controlled risk factors (Journal Watch Sep 7 2004). But does this target make sense for all patients with stable coronary heart disease? In this manufacturer-sponsored trial, investigators randomized 10,001 patients with clinically evident CHD and LDL cholesterol levels of <130 mg/dL to receive either 10 mg or 80 mg of atorvastatin daily.

The 10-mg dose lowered LDL to a mean of 101 mg/dL, while the 80-mg dose resulted in a mean level of 77 mg/dL. The incidence of persistent elevations on liver function tests was higher in the 80-mg group (1.2% vs. 0.2%). After a median follow-up of 4.9 years, the incidence of major cardiovascular events (death from CHD, nonfatal nonprocedural myocardial infarction, stroke, or resuscitation after cardiac arrest) was 8.7% in the 80-mg group and 10.9% in the low-dose group, a significant difference. Overall mortality did not significantly differ between groups.

Comment: These data suggest that more aggressive lowering of LDL benefits patients with stable coronary heart disease -- at least in terms of risk for stroke and MI. An editorialist cautions that, while cardiovascular mortality was lower in the high-dose group, noncardiovascular mortality was higher. This could be a chance finding, and the study was not powered to find differences in mortality, but he advocates for more safety data before widespread adoption of the new LDL target. In the meantime, clinicians will have to weigh the demonstrated benefits of aggressive therapy against remaining uncertainties.

— Kirsten E. Fleischmann, MD, MPH

Published in Journal Watch General Medicine April 1, 2005

Citation(s):

La Rosa JC et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005 Apr 7; 352:1425-35. (early release version: http://content.nejm.org/cgi/content/short/NEJMoa050461)

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

Pitt B. Low-density lipoprotein cholesterol in patients with stable coronary heart disease -- Is it time to shift our goals? N Engl J Med 2005 Apr 7; 352:1483-4. (early release version: http://content.nejm.org/cgi/content/short/NEJMe058052)

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