Combination of Isosorbide Dinitrate and Hydralazine in Blacks with Heart Failure

BACKGROUND We examined whether a fixed dose of both isosorbide dinitrate and hydralazine provides additional benefit in blacks with advanced heart failure, a subgroup previously noted to have a favorable response to this therapy. METHODS A total of 1050 black patients who had New York Heart Association class III or IV heart failure with dilated ventricles were randomly assigned to receive a fixed dose ofisosorbide dinitrate plus hydralazine or placebo in addition to standard therapy for heart failure. The primary end point was a composite score made up of weighted values for death from any cause, a first hospitalization for heart failure, and change in the quality of life. RESULTS The study was terminated early owing to a significantly higher mortality rate in the placebo group than in the group given isosorbide dinitrate plus hydralazine (10.2 percent vs. 6.2 percent, P=0.02). The mean primary composite score was significantly better in the group given isosorbide dinitrate plus hydralazine than in the placebo group (-0.1±1.9 vs. -0.5±2.0, P=0.01; range of possible values, -6 to + 2), as were its individual components (43 percent reduction in the rate of death from any cause [hazard ratio, 0.57; P=0.01] 33 percent relative reduction in the rate of first hospitalization for heart failure [16.4 percent vs. 22.4 percent, P=0.001], and an improvement in the quality of life [change in score, -5.6±20.6 vs. -2.7±21.2, with lower scores indicating better quality of life; P=0.02; range of possible values, 0 to 105]). CONCLUSIONS The addition ofa fixed dose of isosorbide dinitrate plus hydralazine to standard therapy for heart failure including neurohormonal blockers is efficacious and increases survival among black patients with advanced heart failure

Arterial Smooth Muscle Effects of Aldosterone: Action on Ionic Fluxes

1. Aldosterone given acutely to male Wistar rats stimulated ouabain-sensitive and ouabain-insensitive 22Na efflux from tail arteries. 2. These effects of aldosterone seem to depend on the activation of specific mineralocorticoid receptors, as they are blocked by antimineralo-corticoid drugs. 3. The results suggest that aldosterone may have a physiological role in the control of vascular tone.</jats:p

Hemodynamic Patterns in Essential Hypertension

Hemodynamic studies, including cardiac output, arterial blood pressure, run-off index, flow cessation pressure, and blood volume, were performed in 20 normotensive control subjects, 17 labile hypertensive patients and 20 patients with fixed hypertension, 10 of them with a mild elevation of the diastolic pressure and 10 classified as severe because of a diastolic blood pressure above 110 mm. Hg. In labile hypertension cardiac output was elevated, whereas blood volume, peripheral resistance, run-off index and flow cessation pressure were normal when blood pressure was high. This hemodynamic pattern was interpreted as due to an enhanced myocardial contractile energy or a restriction of the capacity vascular bed. In mild fixed hypertension total peripheral resistance and flow cessation pressure were uniformly increased, but cardiac output and run-off index were normal. This pattern may be explained by the influence of flow autoregulation and the barostatic mechanism. In severe fixed hypertension blood volume, cardiac output, and peripheral resistance were found to be high. Renal ischemia and secondary hyperaldosteronism may determine the development of this last stage of hypertension.</jats:p