ABSENCE OF HEMODYNAMIC TOLERANCE TO NICORANDIL IN PATIENTS WITH SEVERE CONGESTIVE-HEART-FAILURE

To evaluate whether hemodynamic tolerance develops to nicorandil, a nitrate and potassium channel opener, 14 patients with chronic heart failure (CHF) were treated with nicorandil and 11 were treated with nitroglycerin (GTN). Doses of GTN or nicorandil were titrated to achieve a greater than or equal to 20% reduction in pulmonary capillary wedge pressure (PCWP) within 1 hour, and the infusion was maintained at a constant rate for 24 hours. Both groups of patients had comparable hemodynamic parameters before drug infusions were started. The fall in PCWP was identical after 1 hour infusion of either GTN or nicorandil. In the GTN group, PCWP was not significantly different from the baseline value at 12 hours; however, in the nicorandil group, PCWP remained significantly lower than the preinfusion value for 24 hours. During the study period changes in plasma atrial natriuretic peptide (ANP) concentrations paralleled and correlated with changes in PCWP (r = 0.84, p < 0.001). These findings indicate that CHF patients develop hemodynamic tolerance to GTN within 12 hours of continuous infusion, but not to nicorandil, which remained hemodynamically effective during the 24-hour period of infusion. Furthermore, plasma ANP concentration may be a useful noninvasive index of hemodynamic tolerance during GTN or nicorandil therapy in patients with CHF.