Usefulness of nicorandil in congestive heart failure

• Published in: The American journal of cardiology Vol. 65; no. 5; pp. 343 - 348
• Main Authors: Galié, Nazzareno, Varani, Elisabetta, Maiello, Luigi, Boriani, Giuseppe, Boschi, Stefano, Binetti, Giorgio, Magnani, Bruno
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.02.1990; Elsevier
• Subjects: Adult; Antianginal agents. Coronary vasodilator agents; Biological and medical sciences; Cardiovascular system; Double-Blind Method; Exercise - physiology; Exercise Test; Female; Heart Failure - drug therapy; Hemodynamics - drug effects; Humans; Male; Medical sciences; Middle Aged; Niacinamide - analogs & derivatives; Niacinamide - therapeutic use; Nicorandil; Pharmacology. Drug treatments; Randomized Controlled Trials as Topic; Time Factors; Vasodilator Agents - therapeutic use; Physical exercise; Human; Heart failure; Chemotherapy; Coronary vasodilator agent; Heart disease; Organic nitrate; Oral administration; Cardiovascular disease; Hemodynamics; Antiarrhythmia agent
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/0002-9149(90)90299-G

Rest and exercise hemodynamic and hormonal effects of nicorandil, a nicotinamide-nitrate vasodilator, were assessed in 9 patients with New York Heart Association class II or III congestive heart failure (CHF) and left ventricular ejection fraction ≤40%. Single oral doses of placebo and 40 and 60 mg of nicorandil were given in a double-blind, randomized trial. Hemodynamic measurements were assessed at rest, up to 8 hours after dose and at peak exercise performed on an upright cycloergometer 1 hour after the dose. Forearm blood flow and venous capacitance were measured by plethysmography 45 minutes after dose. Plasma noradrenaline and plasma renin activity were assessed 1 hour and 2 hours after dose, respectively. Data were analyzed by analysis of variance. Peak effects were observed between 30 and 60 minutes after dose. Mean blood pressure decreased from 86 ± 7 mm Hg after placebo to 78 ± 7 mm Hg after 40 mg (p < 0.05) and to 78 ± 7 mm Hg after 60 mg (p < 0.05) of nicorandil. Mean pulmonary artery pressure decreased from 24 ± 11 to 15 ± 17 mm Hg (p < 0.05) and to 17 ± 7 mm Hg (p < 0.05) and mean pulmonary wedge pressure decreased from 15 ± 8 to 9 ± 4 mm Hg (p < 0.05) and to 10 ± 5 min Hg (p < 0.05). The changes were significant up to 6 to 8 hours after both doses. Cardiac output increased 2 hours after dose from 4.6 ± 0.7 liters/ mm after placebo to 5.5 ± 0.8 liters/min after 60 mg (p < 0.05). At peak exercise mean pulmonary wedge pressure decreased from 29 ± 8 mm Hg after placebo to 24 ± 7 mm Hg (p < 0.05) and to 27 ± 8 mm Hg (difference not significant) after 40 and 60 mg of nicorandil. Venous capacitance increased from 2.9 ± 1.4 ml after placebo to 3.4 ± 1.3 ml after 40 mg of nicorandil (p = 0.1). Cardiac output 1 hour after the meal was 5.7 ± 1 liters/min after placebo and increased to 6.3 ± 1.5 liters/min (p < 0.05) after 40 mg and to 6.2 ± 1 liters/min (p < 0.05) after 60 mg of nicorandil. Plasma renin activity increased from 18.6 ± 29.3 ng/ml/hour after placebo to 24.3 ± 31.1 (p < 0.05) and 22 ± 31.1 ng/ml/hour (p < 0.05) after 40 and 60 mg of nicorandil. Single oral doses of nicorandil in patients with CHF induce favorable changes on rest and exercise hemodynamics up to 6 to 8 hours. An increase of renin activity is also observed.