Impact of Spironolactone on Longitudinal Changes in Health-Related Quality of Life in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial

Abstract

Background— Heart failure (HF) with preserved ejection fraction patients have equally impaired health-related quality of life (HRQL) compared with those with HF with reduced ejection fraction, but limited studies have evaluated the impact of therapies on changes in HRQL. Methods and Results— Patients ≥50 years of age, with symptomatic HF and left ventricular ejection fraction ≥45%, were enrolled in Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) and randomized to spironolactone or placebo. Patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ), which was the primary HRQL instrument, and EQ5D visual analog scale at baseline, 4 months, 12 months, and annually thereafter. McMaster Overall Treatment Evaluation was assessed at 4 and 12 months to assess global change scores. Change scores (+SD) were calculated to determine between-group differences, and multivariable repeated-measures models were created to identify other factors associated with change scores. Paired KCCQ data were available for 91.7% of 3445 TOPCAT patients. By 4 months, the mean change in KCCQ was 7.7±16 and mean change in EQ5D visual analog scale was 4.7±16. Adjusted mean changes in KCCQ for the spironolactone group were significantly better than those for the placebo group at 4-month (1.54 better; P =0.002), 12-month (1.35 better; P =0.02), and 36-month (1.86 better; P =0.02) visits. No between-group differences in EQ5D visual analog scale change scores or McMaster Overall Treatment Evaluation were noted. Older age, obesity, current smoking, New York Heart Association class III/IV, and comorbid illnesses were associated with declines in KCCQ scores. Use of spironolactone was an independent predictor of improved KCCQ scores. Conclusions— In symptomatic HF with preserved ejection fraction patients, use of spironolactone was associated with an improvement in HF-specific HRQL. Several modifiable risk factors were associated with HRQL deterioration. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00094302.

Association of Serial Kansas City Cardiomyopathy Questionnaire Assessments With Death and Hospitalization in Patients With Heart Failure With Preserved and Reduced Ejection Fraction

“…14 There was no significant reduction in the primary outcome with spironolactone, when added to standard medical therapy in the overall population, although there was a significant improvement in the KCCQ Overall Summary score (KCCQ-os). 5 In TOPCAT, however, there were concerns about the validity of data from patients enrolled in Russia and Georgia (48.7% of trial population, 15,16 so we decided, a priori , to exclude patients from Russia and Georgia (n=1,678) in the current analyses, leaving a final analytic cohort from TOPCAT of 1,372 patients (Figure 1). …”

Endothelial mineralocorticoid receptor contributes to systolic dysfunction induced by pressure overload without modulating cardiac hypertrophy or inflammation

“…However, secondary and post hoc analyses revealed that MR antagonism improved quality of life in patients with HFpEF (Lewis et al. 2016) and reduced hospitalization and mortality in those enrolled in the Americas (rather than Eastern Europe) (Pfeffer et al. 2015; Bristow et al.…”

Targeting Obesity and Diabetes to Treat Heart Failure with Preserved Ejection Fraction

“…Surprisingly, the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study, a large randomized, double-blind clinical trial of spironolactone versus placebo in patients with symptomatic HFpEF, did not achieve a significant reduction in the primary composite outcome of time to cardiovascular death from cardiovascular causes, aborted cardiac arrest, or hospitalization for management of HF; however, TOPCAT did demonstrate that spironolactone decreases HF hospitalizations in HFpEF patients (118). Use of spironolactone for HFpEF was associated with an improvement in HF-specific health-related quality of life (119) and, in a separate study, improved exercise tolerance (120). Actually, the beneficial effects of spironolactone in HFpEF may be more significant.…”