Adoption of spironolactone therapy for older patients with heart failure and left ventricular systolic dysfunction in the United States, 1998-2001
ABSTRACT Concerns have been raised about the appropriateness of spironolactone use in some patients with heart failure. We studied the adoption of spironolactone therapy after publication of the Randomized Aldactone Evaluation Study (RALES) in national cohorts of older patients hospitalized for heart failure.
This is a study of serial cross-sectional samples of Medicare beneficiaries > or =65 years old discharged after hospitalization for the primary diagnosis of heart failure and with left ventricular systolic dysfunction. The first sample was discharged before (April 1998 to March 1999, n=9758) and the second sample after (July 2000 to June 2001, n=9468) publication of RALES in September 1999. We assessed spironolactone prescriptions at hospital discharge in patient groups defined by enrollment criteria for the trial. Using multivariable logistic regression, we identified factors independently associated with prescriptions not meeting these criteria. Spironolactone use increased >7-fold (3.0% to 21.3% P<0.0001) after RALES. Of patients meeting enrollment criteria, 24.1% received spironolactone, as compared with 17.4% of those not meeting the criteria. Of all prescriptions after RALES, 30.9% were provided to patients not meeting enrollment criteria. Spironolactone was prescribed to 22.8% of patients with a serum potassium value > or =5.0 mmol/L, to 14.1% with a serum creatinine value > or =2.5 mg/dL, and to 17.3% with severe renal dysfunction (estimated glomerular filtration rate <30 mL.min(-1).1.73 m(-2)). In multivariable analyses, factors associated with prescriptions not meeting enrollment criteria included advanced age, noncardiovascular comorbidities, discharge to skilled nursing facilities, and care provided by physicians without board certification.
Spironolactone prescriptions increased markedly after the publication of RALES, and many treated patients were at risk for hyperkalemia. Simultaneously, many patients who might have benefited were not treated. These findings demonstrate the importance of balancing efforts to enhance use among appropriate patients and minimizing use in patients at risk for adverse events.
SourceAvailable from: Erin M Macdonald[Show abstract] [Hide abstract]
ABSTRACT: Trimethoprim-sulfamethoxazole increases the risk of hyperkalemia when used with spironolactone. We examined whether this drug combination is associated with an increased risk of sudden death, a consequence of severe hyperkalemia. We conducted a population-based nested case-control study involving Ontario residents aged 66 years or older who received spironolactone between Apr. 1, 1994, and Dec. 31, 2011. Within this group, we identified cases as patients who died of sudden death within 14 days after receiving a prescription for trimethoprim-sulfamethoxazole or one of the other study antibiotics (amoxicillin, ciprofloxacin, norfloxacin or nitrofurantoin). For each case, we identified up to 4 controls matched by age and sex. We determined the odds ratio (OR) for the association between sudden death and exposure to each antibiotic relative to amoxicillin, adjusted for predictors of sudden death using a disease risk index. Of the 11 968 patients who died of sudden death while receiving spironolactone, we identified 328 whose death occurred within 14 days after antibiotic exposure. Compared with amoxicillin, trimethoprim-sulfamethoxazole was associated with a more than twofold increase in the risk of sudden death (adjusted OR 2.46, 95% confidence interval [CI] 1.55-3.90). Ciprofloxacin (adjusted OR 1.55, 95% CI 1.02-2.38) and nitrofurantoin (adjusted OR 1.70, 95% CI 1.03-2.79) were also associated with an increased risk of sudden death, although the risk with nitrofurantoin was not apparent in a sensitivity analysis. The antibiotic trimethoprim-sulfamethoxazole was associated with an increased risk of sudden death among older patients taking spironolactone. When clinically appropriate, alternative antibiotics should be considered in these patients. © 8872147 Canada Inc.Canadian Medical Association Journal 02/2015; 187(4). DOI:10.1503/cmaj.140816 · 5.81 Impact Factor
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ABSTRACT: The majority of randomized clinical trials in heart failure with preserved ejection fraction (HFpEF) have failed to show meaningful improvements in clinical outcomes. Recent randomized trials have shown benefits from mineralocorticoid receptor antagonists (MRAs) in the management of HFpEF. This review will focus on new evidence for MRA therapy in patients with HFpEF. Three randomized trials were reviewed: the Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial; the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial; and its echocardiography substudy. The Aldo-DHF trial showed improvements in echocardiographic measures of diastolic function. In the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist trial, hospitalization for heart failure was significantly reduced with MRA therapy with no difference in the primary outcome of cardiovascular death or hospitalization. In patients with high risk, however, there may be a reduction in cardiovascular mortality. We will also briefly discuss finerenone, a new generation MRA associated with a lower incidence of hyperkalemia. New evidence shows that MRA therapy decreases left ventricular mass and left atrial size, reduces hospitalization, and may reduce cardiovascular mortality in patients with high risk.Current Opinion in Cardiology 01/2015; 30(2). DOI:10.1097/HCO.0000000000000147 · 2.59 Impact Factor
Circulation Cardiovascular Quality and Outcomes 11/2014; DOI:10.1161/CIRCOUTCOMES.114.001500 · 5.66 Impact Factor