The Journal of Informed Pharmacotherapy 2000;1:203-204.
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Reviewer: James McCormack, Pharm.D.
Reviewer's email address: email@example.com
Reviewer's profession/specialty: Assoc. Professor, Faculty of Pharmaceutical Sciences, University of British Columbia
Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes
J. The effect of spironolactone on morbidity and mortality in patients with severe heart
failure. N Engl J Med 1999;341:709-17 . PubMed
. PubMed Citation
The objectives of this trial were to determine the benefit on morbidity and mortality of adding low dose (25-50mg/day) spironolactone to patients with severe heart failure already receiving ACE inhibitors, diuretics and digoxin.
1. Was assignment of patients randomized?
Yes, patients meeting the inclusion criteria were randomly assigned to receive 25 mg of oral spironolactone (842 patients) or placebo (841 patients) once daily. After 8 weeks the spironolactone dose could be increased to 50 mg if the patient showed signs or symptoms of progressive heart failure.The results of this trial can be applied to a wide range of patients who are at high risk for cardiovascular events.
2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?
Unable to determine. Two hundred patients in the placebo group and 214 patients in the spironolactone discontinued treatment reportedly due to lack of response, side effects, or for administrative reasons. Whether all patients were followed up at the conclusion of the study was not reported, although patients who discontinued treatment were followed with regular telephone calls to determine their vital status.
Yes. There were no differences in overall adverse effects between the groups; however, 3% more patients withdrew as a result of adverse events in the spironolactone group. There was a difference in the incidence of gynecomastia (9% spironolactone versus 1% on placebo). There was no difference in the incidence of serious hyperkalemia between the groups. Since spironolactone is available as a generic drug, the cost should not be much of an issue.
This study demonstrates that the use of spironolactone can provide a clinically important benefit to patients with Class III and IV heart failure who are already receiving standard therapy (i.e. loop diuretics, ACE inhibitors and digoxin). Given the low incidence of side effects and the low cost of spironolactone, all patients with Class III or IV heart failure should be given a trial of spironolactone. Whether patients with less severe heart failure would benefit is unknown.
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