Spironolactone for heart failure - Diegori.it

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Spironolactone for heart failure13/06/2011 17:04NYHA classChange in NYHA class Placebo SpironolactoneImproved 33% 41%Same 18% 21%Worsened or died 48% 38%Adverse effectsDuring the course of the study, the heart rate, blood pressure, weight and serum sodiumconcentrations did not differ between the two groups.In the spironolactone group, the median potassium concentration rose by 0.3 mmol/l and theserum creatinine rose by approximately 0.1 mg/dl. There was no change in the placebo group.Overall, adverse events were reported in 79% of patients taking placebo and in 82% of those onspironolactone. Discontinuation because of adverse events occurred in only 5% of placebopatients and 8% of spironolactone patients. Most of the adverse events occurred with equalfrequency in both groups, including serious hyperkalemia (10 patients in the placebo group, 14in the spironolactone group).The only adverse effect which happened significantly more often in patients in thespironolactone group was gynecomastia or breast pain, which occurred in 10% of men in thisgroup, vs 1% in the placebo group.Author's discussionThe authors note that the beneficial effects of spironolactone on morbidity and mortalitydemonstrated in this study were observed after 2 to 3 months of treatment and persistedthroughout the study.Recent research has shown that aldosterone can cause myocardial and vascular fibrosis, directvascular damage, baroreceptor dysfunction and can prevent the uptake of norepinephrine by themyocardium. The authors speculate that the beneficial effects of aldosterone receptor blockadeon progressive heart failure and sudden death are in part due to blocking these effects ofaldosterone. The beneficial effects were seen in patients who were almost all receiving ACEinhibitors; this implies that the reduction of aldosterone production by blockade of theangiotensin system alone is not sufficient to prevent the ill effects of aldosterone in heart failure.Although some of the effects of spironolactone could be due to natriuresis and retention ofpotassium, the authors point out that there was no evidence of a significant hemodynamic effectof spironolactone and they do not consider the rise in serum potassium in spironolactone treatedpatients to be clinically significant.Significant hyperkalemia was rare, which the authors attribute to the relatively low dose ofspironolactone used (mean dose 26 mg) and to the exclusion of patients with elevated serumhttp://www.journalclub.org/vol2/a72.htmlPage 4 of 8
Spironolactone for heart failure13/06/2011 17:04creatinine or potassium at baseline. Although gynecomastia and breast pain were significantproblems in men treated with spironolactone, they only led to discontinuation of the drug in 2%of men and may well be a much lesser problem with newer aldosterone receptor blockers thatare under investigation.CommentThis study of spironolactone in patients with severe congestive heart failure revealed a significantreduction (by about 30% relative risk) in death and hospitalizations among treated patients. Thesepatients were receiving reasonable therapy with diuretics, ACE inhibitors and digitalis, and, althoughonly 10% were on beta-blockers, the benefit was, if anything, greater in this subgroup. The results ofthe study should be applicable to a fairly large segment of patients with severe CHF, since theexclusion criteria should not rule out the majority of patients in clinical practice.The authors do not state whether or not baseline aldosterone levels were obtained in these patients. Ifthey were, it would be interesting to see whether the benefit of spironolactone was concentrated inpatients with higher aldosterone levels. If so, the drug could be targetted to those who would benefitthe most.I was initially surprised to see a major pharmaceutical company like Searle sponsoring a trial of suchan old drug, but Searle is also developing a newer aldosterone receptor blocker, eplerenone, whichmay cause less gynecomastia. Whether or not this newer drug will be as effective in CHF remains tobe seen.September 7, 1999ReferencesReferences related to this article from the NLM's PubMed database.Reader CommentsSeptember 12, 1999From: Hans Liedholm [Hans.Liedholm@smi.mas.lu.se]Dear Michael,We read with interest the publication of the results of the RALES study as this adds to the knowledgeon the pharmacological treatment of severe heartfailure (1). Earlier this year two trials on treatmentwith selective beta-blockers were published (2,3). Bisoprolol (CIBIS- II study) and metoprolol(MERIT-HF trial) respectively showed a significant effect on mortality compared to placebo whenadded to conventional treatment. The impact of the results of these trials is considerable and willhttp://www.journalclub.org/vol2/a72.htmlPage 5 of 8
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