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Lower LDL Target for Stable CHD Patients?

The National Cholesterol Education Program has introduced an optional LDL-cholesterol goal of <70 mg/dL for patients at very high risk for coronary heart disease, even when baseline levels are <100 mg/dL (Journal Watch Cardiology Sep 3 2004). Adding to the ongoing debate, researchers have conducted a manufacturer-sponsored, double-blind, international trial in which 10,001 patients (mean age, 61; 81% men; 94% white) with clinically evident stable CHD were randomized to receive daily atorvastatin at either 10 mg (LDL goal, 100 mg/dL) or 80 mg (LDL goal, 75 mg/dL). Patients were randomized only if 8-week run-in treatment with open-label 10-mg atorvastatin achieved an LDL level <130 mg/dL.

A significant difference in LDL level emerged between high-dose and low-dose recipients by 12 weeks after randomization, and it was maintained throughout the 5-year study (mean, 77 mg/dL vs. 101 mg/dL, respectively). The incidence of major cardiovascular events was significantly lower in the high-dose group than in the low-dose group (8.7% vs. 10.9%), with significant differences in nonfatal MI (4.9% vs. 6.2%) and stroke (2.3% vs. 3.1%) and a borderline significant difference in CHD death (2.0% vs. 2.5%). Findings were consistent regardless of age and sex.

The high-dose group had significantly higher rates of drug discontinuation (7.2% vs. 5.3% in the low-dose group) and abnormal liver-function tests (1.2% vs. 0.2%) and a borderline significantly higher incidence of death from noncardiovascular causes (3.2% vs. 2.5%). All-cause mortality incidence was nearly identical in the two groups (about 5.7%). Five cases of rhabdomyolysis were reported: two in the high-dose group, three in the low-dose group.

Comment: These findings in stable CHD patients lend support to the case for lower LDL targets. However, the higher incidence of death from noncardiovascular causes in the high-dose group (although perhaps due to chance) prompts an editorialist to call for further research to establish the safety and effectiveness of 80-mg atorvastatin and to ask whether other means of achieving very low LDL levels could prove safer. Another important caveat is that the study subjects, selected for having achieved LDL levels <130 mg/dL while on 10-mg atorvastatin, might have been a group particularly responsive to this statin.

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology December 30, 2005

Citation(s):

LaRosa JC et al. for the Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005 Apr 7; 352:1425-35.

• 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.

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