INFLUENCE OF PRERANDOMIZATION (BASE-LINE) VARIABLES ON MORTALITY AND ON THE REDUCTION OF MORTALITY BY ENALAPRIL - VETERANS AFFAIRS COOPERATIVE STUDY ON VASODILATOR THERAPY OF HEART-FAILURE (V-HEFT-II)

Background. The effects of hydralazine plus isosorbide dinitrate were compared with those of enalapril in 804 men receiving digoxin and diur etic therapy for chronic congestive heart failure (CHF) in the Departm ent of Veterans Affairs Cooperative Vasodilator-Heart Failure Trial (V -HeFT II). Methods and Results. Patients were randomly assigned to rec eive 20 mg of enalapril or 300 mg of hydralazine plus 160 mg of isosor bide dinitrate daily. At 2 years, treatment with enalapril resulted in a significant (28%) reduction in mortality relative to the active con trol treatment. Baseline variables were examined to determine their im pact on risk of mortality and on relative response to treatment. Morta lity rates were significantly higher in patients with severe ventricul ar arrhythmias; in patients with low baseline ejection fractions, low peak oxygen consumption, and low systolic blood pressures; in patients with high cardiothoracic ratios, high scores indicating greater impai rment on a quality-of-life questionnaire, and high plasma norepinephri ne or renin levels; and in patients in New York Heart Association (NYH A) classes III and IV. Coronary artery disease, duration of CHF, and p atient age were not predictive of mortality. Enalapril reduced mortali ty significantly compared with hydralazine/isosorbide dinitrate in pat ient subgroups with high plasma renin or norepinephrine levels and in patients with low cardiothoracic ratios. Furthermore, enalapril confer red significantly greater protection from mortality than hydralazine/i sosorbide dinitrate in patients in NYHA classes I and II and in patien ts without arrhythmias or with less-than-or-equal-to 10 premature vent ricular contractions per hour. Conclusions. Of the prerandomization ch aracteristics that were predictive of mortality in patients with CHF, only neurohormone measurements, cardiothoracic ratios, arrhythmia seve rity, and NYHA class identified subgroups of patients who benefited mo st from treatment with enalapril; a treatment interaction across strat a was detected only for plasma norepinephrine and NYHA class. In no pa tient subgroup was the mortality with enalapril treatment significantl y higher than the mortality with hydralazine/isosorbide dinitrate trea tment.