Clinical and neurohormonal effects of nicardipine hydrochloride in patients with severe chronic heart failure receiving angiotensin-converting enzyme inhibitor therapy.
It has been proposed that worsening of heart failure with dihydropyridines, such as nicardipine, is related to the activation of the neuroendocrine system. To test this, we evaluated 20 patients with severe heart failure (mean age, 55 +/- 13 years; New York Heart Association functional class III; left ventricular ejection fraction, 18% +/- 8% on maintenance therapy with captopril, digoxin, and diuretics) who were randomized to nicardipine (60 or 90 mg/d) or placebo during a 4-month double-blind protocol. The following measurements were obtained at baseline, monthly, and at 4 months or last follow-up visit: rest and exercise radionuclide ventriculography, maximal treadmill time, 6-minute walking test distance, serum norepinephrine and aldosterone concentrations, and plasma renin activity. During the follow-up period, worsening of heart failure occurred in 6 patients in the nicardipine group and in 2 patients in the placebo group (p = 0.06). The maximal treadmill time for a 6-minute walking distance and exercise radionuclide ejection fraction at the last follow-up visit did not change in patients who did not deteriorate with heart failure in the placebo or nicardipine groups as compared with baseline values. In this study group of patients with severe heart failure receiving therapy with digoxin, captopril, and diuretics, nicardipine was associated with worsening heart failure without an apparent activation of the neurohormones. However, because of the small number of patients and a significant number of patients who deteriorated during the follow-up period, no definitive conclusions can be made.
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Northwestern University Medical School, Division of Cardiology, 250 East Superior Street, Wesley 524, Chicago, IL 60611, USA.
Hall
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Reddy
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Gheorghiade
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D000368:Aged; D000450:Aldosterone / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002216:Captopril / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000627:therapeutic use; D004077:Digoxin / Q000627:therapeutic use; D018450:Disease Progression; D004232:Diuretics / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005080:Exercise Test; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009490:Neurosecretory Systems / Q000187:drug effects*; D009529:Nicardipine / Q000627:therapeutic use*; D009638:Norepinephrine / Q000097:blood; D012083:Renin / Q000097:blood; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000187:drug effects; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D004232:Diuretics; D000450:Aldosterone; D004077:Digoxin; D002216:Captopril; D009529:Nicardipine; D012083:Renin; D009638:Norepinephrine