Veterans Administration Cooperative Study on Vasodilator Therapy of Heart Failure: influence of prerandomization variables on the reduction of mortality by treatment with hydralazine and isosorbide dinitrate.

The Veterans Administration Cooperative Study on Vasodilator Therapy of Heart Failure was designed to determine whether vasodilator drugs could alter the survival of patients with chronic congestive heart failure treated with digoxin and diuretics. Among the 642 patients entered into the study, 273 were randomly assigned to placebo, 186 were randomly assigned to the combination of hydralazine and isosorbide dinitrate, and 183 patients were randomly assigned to prazosin; all patients were followed for periods ranging from 6 months to 5.7 years. Treatment with hydralazine-nitrate produced a 28% reduction in mortality compared with that in patients receiving placebo (95% confidence interval, 3% to 46%), whereas prazosin exerted no apparent beneficial effect. Data were further examined to determine if any baseline variables had an impact on the response to treatment. Mortality in the placebo group was higher in those with coronary artery disease, with a history of antiarrhythmic drug use, and with values lower than the median for ejection fraction and exercise tolerance. A reduction in mortality with hydralazine-isosorbide dinitrate was observed in all of the above pairs of subgroups as well as in those above and below 60 years of age and those with and without a history of hypertension or excess alcohol ingestion. The benefit of hydralazine and isosorbide dinitrate was particularly prominent in younger patients with a lower ejection fraction and those with a history of hypertension and without an alcoholic history.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study.

To evaluate the effects of vasodilator therapy on mortality among patients with chronic congestive heart failure, we randomly assigned 642 men with impaired cardiac function and reduced exercise tolerance who were taking digoxin and a diuretic to receive additional double-blind treatment with placebo, prazosin (20 mg per day), or the combination of hydralazine (300 mg per day) and isosorbide dinitrate (160 mg per day). Follow-up averaged 2.3 years (range, 6 months to 5.7 years). Mortality over the entire follow-up period was lower in the group that received hydralazine and isosorbide dinitrate than in the placebo group. This difference was of borderline statistical significance. For mortality by two years, a major end point specified in the protocol, the risk reduction among patients treated with both hydralazine and isosorbide dinitrate was 34 percent (P less than 0.028). The cumulative mortality rates at two years were 25.6 percent in the hydralazine--isosorbide dinitrate group and 34.3 percent in the placebo group; at three years, the mortality rate was 36.2 percent versus 46.9 percent. The mortality-risk reduction in the group treated with hydralazine and isosorbide dinitrate was 36 percent by three years. The mortality in the prazosin group was similar to that in the placebo group. Left ventricular ejection fraction (measured sequentially) rose significantly at eight weeks and at one year in the group treated with hydralazine and isosorbide dinitrate but not in the placebo or prazosin groups. Our data suggest that the addition of hydralazine and isosorbide dinitrate to the therapeutic regimen of digoxin and diuretics in patients with chronic congestive heart failure can have a favorable effect on left ventricular function and mortality.

Diagnosis of aortic stenosis in older age groups using external carotid pulse recording and phonocardiography.

Measurements made from carotid pulse tracings and phonocardiograms are helpful in the prediction of severe aortic stenosis in young patients. In the elderly, however, analysis of the carotid pulse tracing and, in particular, its maximum rate of rise has proved unreliable because the range of normal values for this age group has not been established. Consequently, we studied 44 young normal and 44 older normal subjects, 15 older patients with systolic hypertension, and 36 older patients with significant aortic stenosis. Measurements obtained from the carotid pulse included the left ventricular ejection time, upstroke time, half-rise time, and the maximum rate of rise. The peak of the systolic murmur in aortic stenosis was measured phonocardiographically from the Q wave of the simultaneously recorded electrocardiogram (QP interval). The results confirm that the maximum rate of rise of the carotid pulse of normal older subjects is much more rapid than that of young subjects. Among elderly patients with aortic stenosis, the maximum rate of rise falls within the range of the normal young. Measurement of the half-rise time is imprecise, and there is considerable overlap with the normal. This is also true of left ventricular ejection time. The upstroke time is unreliable because of wave distortion produced by the arteriosclerotic vascular bed. The two most valuable and easily recorded measurements are the maximum rate of rise and the QP interval. A maximum rate of rise of more than 1000 mmHg/s and a QP interval of less than 220 ms argue strongly against the diagnosis of severe aortic stenosis. These measurements provide a simple, non-invasive means of avoiding left heart catheterisation in older subjects suspected of having severe aortic stenosis.