By Laurie Brunette and Asher Kimchi M.D.

San Francisco, CA - Statins are known to reduce the rate of major cardiovascular events through their lipid lowering effects, but their potential benefit as treatment for HF is largely unexplored. Kiran K. Khush et al from University of California, San Francisco School of Medicine compared the effects of two doses of the same statin formulation to determine their impact on the incidence of hospitalization for HF among the two treatment arms. This study, which was published in the February 6, 2007 issue of Circulation, found that intensive treatment with atorvastatin in patients with stable coronary artery disease significantly reduced subsequent hospitalizations for HF compared with low-dose therapy. This benefit was most pronounced in patients with a history of HF.

This study of 10,001 patients included men and women 35 to 75 years old with clinically evident coronary heart disease (CHD), defined as previous myocardial infarction (MI), prior or current angina with objective evidence of CHD, or a history of coronary revascularization. A history of HF was present in 7.8% of patients. At the start of the study, patients discontinued use of any lipid-lowering drugs. Patients entered the trial if their LDL cholesterol was <130 mg/dL after an 8-week run-in trial on 10 mg/d atorvastatin. These patients were randomly assigned to double-blind therapy with either 10-mg (low-dose) or 80-mg (high-dose) atorvastatin daily. The median follow-up period was 4.9 years. A primary efficacy outcome was the occurrence of a major cardiovascular event, defined as nonfatal, non-procedure related MI, resuscitated cardiac arrest, stroke, or CHD death. A secondary efficacy outcome was defined as hospitalization for a primary diagnosis of HF.

The incidence of hospitalization for HF was 2.4% in the 80-mg arm and 3.3% in the 10-mg arm (hazard ratio, 0.74; 95% confidence interval, 0.59 to 0.94; P=0.0116). In patients with a previous history of HF, the benefits of the higher dose were much more pronounced. Among these patients, the incidence of hospitalization for HF was 10.6% in the 80-mg arm and 17.3% in the 10-mg arm (hazard ratio, 0.59; 95% confidence interval, 0.4 to 0.88; P=0.009). Among patients without a history of HF, the rates of hospitalization for HF were much lower: 1.8% in the 80-mg group versus 2.0% in the 10-mg group (hazard ratio, 0.87; 95% confidence interval, 0.64 to 1.16; P=0.34). Thus, the absolute risk reduction in hospitalization for HF for the high-dose group was much greater in patients with a history of HF than without. For each 1 mg/dL reduction in LDL cholesterol, the risk of hospitalization for HF decreased by 0.6% (P=0.007). Of those patients with antecedent myocardial ischemia or MI, only 15.7% experienced their MI or angina in the 3 months preceding HF hospitalization. A significant difference between the blood pressure responses between the 2 treatment groups was not detected.

This study concludes that high-dose compared with low-dose atorvastatin significantly reduced the incidence of hospitalization for HF in patients with stable CHD. This benefit was most pronounced in patients with a history of HF and is unlikely due primarily to a reduction in interim coronary events or differences in blood pressure. The mechanism behind this dose-related effect remains unknown, but may be do to other factors besides the lipid-lowering effects of the statin therapy.

Co-authors: David D. Waters, MD; Vera Bittner, MD; Prakash C. Deedwania, MD; John J.P. Kastelein, MD; Sandra J. Lewis, MD; Nanette K. Wegner, MD