Spironolactone for heart failure - Diegori.it

More documents

Recommendations

Info

Spironolactone for heart failure13/06/2011 17:04transplantation.Potassium > 5.0 mmol/l or creatinine > 2.5 mg/dl.Primary hepatic failure; active cancer.Concommitent therapyTreatment with digitalis and vasodilators was allowed.Treatment with potassium sparing diuretics was not permitted.Potassium supplementation was not recommended unless serum potassium was less than3.5 mmol/l.InterventionPatients were randomized to either 25 mg of spironolactone daily or placebo. This dose couldbe increased to 50 mg daily after 8 weeks if there was evidence for progression of heart failure inthe absence of hyperkalemia.The dose could be decreased to every other day if hyperkalemia developed, but it wasrecommended that the dose of ACE inhibitors be decreased first. Study medication could bewithheld for medical reasons, including hyperkalemia or creatinine > 4.0 mg/dl.Follow-upClinical and laboratory evaluation were carried out every four weeks for the first twelve weeks,every 3 months for the rest of the first year and every 6 months thereafter. An additional serumpotassium measurement was performed at 9 weeks in those patients in whom the dose wasincreased at 8 weeks.AnalysisThe primary endpoint was all-cause mortality, analyzed by intention to treat.Secondary endpoints included cardiac mortality, hospitalization for cardiac causes, death orhospitalization for cardiac causes and change in NYHA class.Predefined subgroups for analysis of efficacy were ejection fraction, cause of heart failure,serum creatinine, age, use of ACE inhibitor and digoxin.ResultsPatientsA total of 1663 patients from 195 centers were randomized (822 to spironolactone, 841 toplacebo), between March 24, 1995 and December 31, 1996. Analysis was terminated on August24, 1998 (16 months early) after interim analysis demonstrated efficacy of the study drugexceeding preset limits.http://www.journalclub.org/vol2/a72.htmlPage 2 of 8
Spironolactone for heart failure13/06/2011 17:04The groups were well matched at baseline. Pertinent characteristics included (approximateaverage of both groups, unless otherwise indicated):Age 65; white 86%; male 73%BP 122/75; heart rate 81NYHAClass III: placebo - 69%; spironolactone - 72% (not significantly different)Class IV: placebo - 31%; spironolactone - 27% (nsd)LV ejection fraction: 25.5%; cause of CHF ischemic in 55%MedicationsAll were on loop diuretics95% were on an ACEI. Mean dose of captopril was 62 mg, of enalapril 15 mg, oflisinopril 14 mg.Digitalis 74%Aspirin 37%Beta blockers 10%Potassium supplements 28%Discontinuation of treatment occurred in 200 patients in the placebo group and in 214 in thespironolactone group (for lack of response, adverse effects or administrative reasons).Mean follow-up was 24 months.SurvivalCause of death Spironolactone Placebo RR and P-valueAll-cause 284 (35%) 386 (46%) 0.70; p 1.2 mg/dl), use of digitalis, use of ACEI, sex, median serum potassium (< or > 4.2 mmol/l),NYHA class (III or IV), beta-blocker use, and use of potassium supplements.HospitalizationA total of 336 patients in the placebo group (40%) were hospitalized for cardiac causes, vs. 260in the spironolactone group (32%), for a RR of 0.70 (p
Page 1: Spironolactone for heart failure13/
Page 5 and 6: Spironolactone for heart failure13/
Page 7 and 8: Spironolactone for heart failure13/

Spironolactone for heart failure - Diegori.it

Create successful ePaper yourself

Delete template?

Save as template?