American Heart Association Scientific Sessions: Isosorbide Dinitrate/Hydralazine Combination for African-American Patients with Heart Failure
Speaker: Ann L. Taylor, MD, Professor of Medicine and Associate Dean for Faculty Affairs, University of Minnesota Medical School, Minneapolis, Minnesota
The addition of a nitric oxide-enhancing, fixed-dose combination of isosorbide dinitrate plus hydralazine (ISDN/HYD) (BiDil®, NitroMed) to standard therapy for heart failure increases survival significantly compared with standard therapy alone.
A total of 1,050 African-American patients with New York Heart Association (NYHA) class III or IV heart failure with dilated ventricles were enrolled into the African-American Heart Failure Trial (A-HeFT). They were randomly assigned to receive a fixed dose of ISDN/HYD or placebo. The initial dose of ISDN/HYD was 37.5 mg/20 mg three times daily. The dose was then increased to two tablets three times a day, for a total dose of 225 mg/120 mg, depending on the absence of drug-induced side effects. cheap generic viagra
The primary endpoint was a composite score made up of weighted values for death from any cause, a first hospitalization for heart failure during the 18-month follow-up period, and a change in quality of life at six months.
On the unanimous recommendation of the independent data and safety monitoring board, the study was terminated early on July 19, 2004, after 1,050 of the planned 1,100 patients had undergone randomization as a result of the significantly higher mortality rate in the placebo group compared with the ISDN/HYD group. When the trial was halted, the mortality rate was 10.2% in the placebo group (54 patients had died), compared with 6.2% in the ISDN/HYD group (32 patients had
died), for a significant 43% improvement in survival (P = .01). The mean duration of follow-up was 10 months.
The rate for a first hospitalization was reduced by 33% in the active-treatment group; the actual rates for a first hospitalization were 16.4% for the treated patients and 22.4% for those taking placebo. Median quality-of-life scores also improved more in the ISDN/HYD patients than in the placebo group, with questionnaire scores of -5.6 ± 20.6 versus -2.7 ± 21.2, respectively. (Lower scores indicated a better quality of life.)
Isotope versus Vasodilator Therapy During Hospitalization for Heart Failure
Speaker: Uri Elkayam, MD, Professor of Medicine, Division of Cardiovascular Medicine, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
In an assessment of the use of isotopes and vasodilator therapy in hospitalized patients with recurrent heart failure (HF), inotropes were associated with an increased risk of death. Patients who received vasodilator medications such as nesiritide (Natrecor®, Scios) had no increased risk.
Initially, 433 patients hospitalized for recurrent HF were enrolled in the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial to determine whether pulmonary artery catheterization (PAC) would improve clinical outcomes in these patients. Patients were randomly assigned to guided therapy using PAC plus clinical assessment or clinical assessment alone.
The use of PAC to lower pulmonary capillary wedge pressure (PCWP) without a specified treatment regimen had no impact on mortality and hospitalization. Whereas the routine use of PAC in hospitalized patients with recurrent HF is not generally indicated, it may result in greater functional improvement. It appears reasonable, therefore, to use PAC to tailor therapy in patients with persistent symptoms of HF.
Because intravenous (IV) inotropes and vasodilators are frequently used during hospitalization for HF and may affect outcomes, predictors of inotrope and vasodilator use and subsequent events for the patients in the ESCAPE trial were identified. Isotropes were used in 43% of patients; low sodium, low blood pressure, and high cardiac filling pressures, when known, were predictors of inotrope use, and the study site was the only independent predictor. Vasodilators were used in 29% of patients, and their administration was predicted by PCWP.
After an adjustment for renal function and blood pressure was made, inotrope usage was associated with an increased risk of death, with a hazard ratio (HR) of 1.75 (P = .032) and an increased risk of death plus hospitalization, with an HR of 2.12 (P < .001). The increased six-month mortality associated with inotrope use may be a reflection of unmeasured assessment factors triggering inotrope use or a late deleterious impact of inotrope use during hospitalization.
Vasodilator use was not associated with any increase in risk, whether or not baseline variables were adjusted.