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(Circulation. 2007;115:576-583.)
© 2007 American Heart Association, Inc.

Heart Failure

Effect of High-Dose Atorvastatin on Hospitalizations for Heart Failure

Subgroup Analysis of the Treating to New Targets (TNT) Study

Kiran K. Khush, MD; David D. Waters, MD; Vera Bittner, MD; Prakash C. Deedwania, MD; John J.P. Kastelein, MD; Sandra J. Lewis, MD; Nanette K. Wenger, MD

From the Divisions of Cardiology, University of California, San Francisco School of Medicine, San Francisco, Calif (K.K.K., D.D.W.); Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham (V.B.); UCSF School of Medicine, Fresno, Calif (P.C.D.); Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands (J.J.P.K.); Portland Cardiovascular Institute, Portland, Ore (S.J.L.); and Emory University School of Medicine, Atlanta, Ga (N.K.W.).

Correspondence to David D. Waters, MD, Division of Cardiology, Room 5G1, San Francisco General Hospital, 1001 Potrero Ave, San Francisco, CA 94965. E-mail dwaters{at}medsfgh.ucsf.edu

Received March 8, 2006; accepted November 3, 2006.

Background— Statins reduce the rate of major cardiovascular events in high-risk patients, but their potential benefit as treatment for heart failure (HF) is less clear.

Methods and Results— Patients (n=10 001) with stable coronary disease were randomized to treatment with atorvastatin 80 or 10 mg/d and followed up for a median of 4.9 years. A history of HF was present in 7.8% of patients. A known ejection fraction <30% and advanced HF were exclusion criteria for the study. A predefined secondary end point of the study was hospitalization for 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). The treatment effect of the higher dose was more marked in patients with a history of HF: 17.3% versus 10.6% in the 10- and 80-mg arms, respectively (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 and 2.0% in the 10-mg group (hazard ratio, 0.87; 95% confidence interval, 0.64 to 1.16; P=0.34). Only one third of patients hospitalized for HF had evidence of preceding angina or myocardial infarction during the study period. Blood pressure was almost identical during follow-up in the treatment groups.

Conclusions— Compared with a lower dose, intensive treatment with atorvastatin in patients with stable coronary disease significantly reduces hospitalizations for HF. In a post hoc analysis, this benefit was observed only in patients with a history of HF. The mechanism accounting for this benefit is unlikely to be due primarily to a reduction in interim coronary events or differences in blood pressure.

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