Published Online
on March 19, 2007

A more recent version of this article appeared on April 3, 2007

This Article Full Text (PDF) CME: Take the course for this article: Circulation: April 3, 2007, Volume 115, Number 13 All Versions of this Article: 115/13/1747    most recent CIRCULATIONAHA.106.644013v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Taylor, A. L. Search for Related Content PubMed PubMed Citation Articles by Taylor, A. L. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Heart Failure Hazardous Substances DB HYDRALAZINE HYDROCHLORIDE ISOSORBIDE DINITRATE Related Collections Other heart failure Congestive Other Treatment Related Article

Submitted on June 8, 2006
Accepted on November 20, 2006

Early and Sustained Benefit on Event-Free Survival and Heart Failure Hospitalization From Fixed-Dose Combination of Isosorbide Dinitrate/Hydralazine. Consistency Across Subgroups in the African-American Heart Failure Trial

Anne L. Taylor MD^*, Susan Ziesche RN, Clyde W. Yancy MD, Peter Carson MD, Keith Ferdinand MD, Malcolm Taylor MD, Kirkwood Adams MD, Adeoye Y. Olukotun MD, Elizabeth Ofili MD, S. William Tam PhD, Michael L. Sabolinski MD, Manuel Worcel MD, Jay N. Cohn MD, on behalf of the African-American Heart Failure Trial Investigators

From the Department of Medicine (A.L.T., J.N.C.), University of Minnesota, Minneapolis, Minn; Minneapolis Veterans Affairs Medical Center (S.Z.), Minneapolis, Minn; Baylor University Medical Center at Dallas (C.W.Y.), Dallas, Tex; Veterans Affairs Medical Center (P.C.), Washington, DC; Xavier University of Louisiana (K.F.), New Orleans; Association of Black Cardiologists (M.T.), Jackson, Miss; University of North Carolina (K.A.), Chapel Hill; Clinical and Regulatory Strategies, LLC (A.Y.O.), Princeton, NJ; Moorehouse School of Medicine (E.O.), Atlanta, Ga; and NitroMed, Inc (S.W.T., M.L.S., M.W.), Lexington, Mass.

^* To whom correspondence should be addressed. E-mail: taylo135{at}umn.edu.

Background--We previously reported that the fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride (FDC I/H) significantly decreased the risk of all-cause death and first hospitalization for heart failure (HF) and improved quality of life in patients with New York Heart Association class III or IV heart failure in the African-American Heart Failure Trial (A-HeFT). The current analyses further define the effect of FDC I/H on the timing of event-free survival (mortality or first hospitalization for HF) and time to first hospitalization for HF, as well as effects by subgroups and effects on cause-specific mortality.

Methods and Results--Kaplan-Meier analyses of the 1050 A-HeFT patients on standard neurohormonal blockade demonstrated that FDC I/H produced a 37% improvement in event-free survival (P<0.001) and a 39% reduction in the risk for first hospitalization for HF (P<0.001). These benefits appeared to emerge early (at 50 days of treatment) and were sustained through the duration of the trial. Subgroup analyses of treatment effect by age, sex, baseline blood pressure, history of chronic renal insufficiency, presence of diabetes mellitus, cause of HF, and baseline medication usage demonstrated consistent beneficial effect of FDC I/H on the primary composite score and event-free survival across all subgroups. Mortality from pump failure was reduced by 75% (P=0.012).

Conclusions--FDC I/H treatment of black patients with moderate to severe HF who were taking neurohormonal blockers produced early and sustained significant improvement in event-free survival and hospitalization for HF in the A-HeFT cohort, with significant reduction in mortality from cardiovascular and pump failure deaths. The treatment effects on the primary composite end point and event-free survival were consistent across subgroups.

Key words: heart failure • cardiovascular diseases • nitric oxide • African Americans • trials

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