Adoption of Spironolactone Therapy for Older Patients With Heart Failure and Left Ventricular Systolic Dysfunction in the United States, 1998–2001

Abstract

Background-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. Methods and Results-This is a study of serial cross-sectional samples of Medicare beneficiaries Ն65 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) and the second sample after (July 2000 to June 2001, nϭ9468) 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 Ͼ7-fold (3.0% to 21.3% PϽ0.0001) 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 Ն5.0 mmol/L, to 14.1% with a serum creatinine value Ն2.5 mg/dL, and to 17.3% with severe renal dysfunction (estimated glomerular filtration rate Ͻ30 mL · min Ϫ1 · 1.73 m Ϫ2 ). 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. Conclusions-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.

Persistent Use of Evidence-Based Pharmacotherapy in Heart Failure Is Associated With Improved Outcomes

“…Risk of renal side effects and hyperkalemia in older patients could explain low persistence for treatment with RASi or spironolactone, as well as for combination treatment with RASi and spironolactone in this population. 12 Notably, an increased number of concomitant medications was associated with persistence of treatment, an important finding because treatment of HF often involves polypharmacy. Also, increased severity of HF did not worsen persistence, in contrast to studies that demonstrated risk-treatment mismatch in the pharmacotherapy of HF.…”

“…In the Randomized Aldactone Evaluation Study (RALES), spironolactone treatment reduced mortality in severe HF by 30%. 11 But later studies have demonstrated increased risk of hyperkalemia 12,19 and increased mortality associated with spironolactone treatment in chronic HF, 25 which could explain why the benefit of spironolactone treatment is not reflected in increased mortality in nonpersistent patients.…”

Trimethoprim–sulfamethoxazole and risk of sudden death among patients taking spironolactone

“…1,2 Although spironolactone is generally well tolerated, hyperkalemia is a potentially life-threatening adverse effect of the drug in clinical practice. [3][4][5] Strategies for mitigating the risk of serious hyperkalemia include cautious dosing of spironolactone, close monitoring of electrolyte levels and avoidance of other drugs that cause hyperkalemia.…”

ACC/AHA 2008 Performance Measures for Adults With ST-Elevation and Non–ST-Elevation Myocardial Infarction

“…Accordingly, the writing committee felt that initiation of aldosterone blockade as a layered therapy (in patients treated with ACEI and beta-blockers) may be most appropriate in the early postdischarge setting. Finally, the writing committee also had some concerns about recent evidence in regard to the use of aldosterone blockade in patients with contraindications to this therapy, 60 which in some cases puts patients at risk for hyperkalemia. The committee believed that, in addition to an outpatient measure for the use of aldosterone antagonists, a parallel measure of inappropriate use may be warranted.…”