Spironolactone and Outcomes in Older Patients with Heart Failure and Reduced Ejection Fraction

Abstract

Background: The efficacy of mineralocorticoid receptor antagonists or aldosterone antagonists in heart failure with reduced ejection fraction (HFrEF) is well known. Less is known about their effectiveness in real-world older patients with HFrEF.

Methods: Of the 8206 patients with heart failure and ejection fraction ≤35% without prior spironolactone use in the Medicare-linked OPTIMIZE-HF registry, 6986 were eligible for spironolactone therapy based on serum creatinine criteria (men ≤2.5 mg/dL, women ≤2.0 mg/dL) and 865 received a discharge prescription for spironolactone. Using propensity scores for spironolactone use, we assembled a matched cohort of 1724 (862 pairs) patients receiving and not receiving spironolactone, balanced on 58 baseline characteristics (Creatinine Cohort: mean age, 75 years, 42% women, 17% African American). We repeated the above process to assemble a secondary matched cohort of 1638 (819 pairs) patients with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m² (eGFR Cohort: mean age, 75 years, 42% women, 17% African American).

Results: In the matched Creatinine Cohort, spironolactone-associated hazard ratios (95% confidence intervals) for all-cause mortality, heart failure readmission, and combined endpoint of heart failure readmission or all-cause mortality were 0.92 (0.81-1.03), 0.87 (0.77-0.99), and 0.87 (0.79-0.97), respectively. Respective hazard ratios (95% confidence intervals) in the matched eGFR Cohort were 0.87 (0.77-0.98), 0.92 (0.80-1.05), and 0.91 (0.82-1.02).

Conclusions: These findings provide evidence of consistent, albeit modest, clinical effectiveness of spironolactone in older patients with HFrEF regardless of renal eligibility criteria used. Additional strategies are needed to improve the effectiveness of aldosterone antagonists in clinical practice.

Keywords: Ejection fraction; Heart failure; Mortality; Readmission; Spironolactone.

Figure 1.

Flow chart displaying assembly of propensity score-matched Creatinine Cohort (serum creatinine ≤2.5mg/dL for men and ≤2.0mg/dL for women) and eGFR Cohort (estimated glomerular filtration rate ≥30 mL/min/1.73 m²) of patients with heart failure, left ventricular ejection fraction ≤35%, with no prior spironolactone therapy

Figure 2.

Love plot displaying absolute standardized differences for 58 baseline characteristics between patients receiving and not receiving a discharge prescription for spironolactone, before and after propensity score matching. Data based on patients with heart failure, left ventricular ejection fraction ≤35%, no prior spironolactone therapy, and serum creatinine ≤2.5mg/dL for men and ≤2.0mg/dL for women. A standardized difference of 0% indicates no residual bias and values <10% indicate inconsequential bias (ACE=angiotensin-converting enzyme; ARB=angiotensin receptor blockers; BP=blood pressure; CCB= calcium channel blocker; COPD=chronic obstructive pulmonary disease)

Figure 3.

Kaplan Meier plots for outcomes by discharge prescription for spironolactone in patients with heart failure, left ventricular ejection fraction ≤35%, no prior spironolactone therapy, and serum creatinine ≤2.5mg/dL for men and ≤2.0mg/dL for women (CI= confidence interval)

Figure 4.

Subgroup analyses for the combined endpoint by discharge prescription for spironolactone in 1724 propensity score-matched patients with heart failure, left ventricular ejection fraction ≤35%, no prior spironolactone therapy, and serum creatinine ≤2.5mg/dL for men and ≤2.0mg/dL for women

Figure 5.

Kaplan Meier plots for outcomes by discharge prescription for spironolactone in patients with heart failure, left ventricular ejection fraction ≤35%, no prior spironolactone therapy, and estimated glomerular filtration rate ≥30 mL/min/1.73 m² (CI=confidence interval)