What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Heart failure with preserved ejection fraction (n=53878). Intervention: Pharmacologic interventions vs. Diuretic or placebo. Primary outcome: All-cause mortality (RR 0.99, 95% CI 0.92-1.06, p=0.70).

What question did this study set out to answer?

To determine the effects of pharmacologic interventions on exercise capacity, diastolic function, and mortality in heart failure with preserved ejection fraction.

May 15, 2026

Effects of Treatment on Exercise Tolerance, Cardiac Function, and Mortality in Heart Failure With Preserved Ejection Fraction

Key Result

Pharmacotherapy in heart failure with preserved ejection fraction did not improve all-cause mortality in randomized trials (RR 0.99; 95% CI 0.92-1.06; p=0.70), though it improved exercise tolerance.

Key Points

To determine the effects of pharmacologic interventions on exercise capacity, diastolic function, and mortality in heart failure with preserved ejection fraction.
Conducted a meta-analysis of trials comparing trial drug to diuretic or placebo
Assessed exercise tolerance using treadmill time, measured diastolic function by E/A ratio
Included data from 53,878 patients across 30 reports, with 18 randomized controlled trials.
In randomized trials, exercise tolerance improved with combined therapy (weighted MD = 51.5; p < 0.001)
No change in E/A ratio measurements was observed (weighted MD = -0.01; p = 0.54)
All-cause mortality was not significantly improved by therapy (RR: 0.99; p = 0.70), although observational reports showed a reduction (RR: 0.80; p = 0.27) before adjustment.

Study Design

Type

Meta-Analysis (n=53,878)

Structured PICO

Do pharmacologic interventions reduce mortality or improve exercise tolerance and diastolic function in patients with heart failure with preserved ejection fraction?

Population

53,878 patients with heart failure with preserved ejection fraction pooled from 30 published reports (18 randomized controlled trials n=11,253 and 12 observational studies n=42,625)

Intervention

Pharmacologic interventions (trial drug)

Comparator

Diuretic or placebo

Outcome

모든 원인에 의한 사망률hard clinical

In a meta-analysis of HFpEF trials, pharmacotherapy improved exercise tolerance but failed to demonstrate a significant reduction in all-cause mortality.

Main Result

Effect estimate: RR 0.99 (95% CI 0.92-1.06)

p-value: p=0.70

Abstract

OBJECTIVES: We sought to determine whether pharmacologic interventions changed exercise capacity, diastolic function, and mortality in a meta-analysis of trials in heart failure with preserved ejection fraction. BACKGROUND: Treatment strategies for heart failure with preserved ejection fraction remain unproven despite several large-scale trials. METHODS: Trials were included in the systematic review where clear comparisons between trial drug and diuretic or placebo were available. Exercise tolerance was assessed by treadmill time, and changes in diastolic function were quantified by transmitral flow (E/A ratio). The primary outcome was all-cause mortality. Weighted mean differences (MDs) and relative risks (RRs), along with their corresponding 95% confidence intervals (CIs), were computed using random-effects models for continuous and dichotomous variables, respectively. The impact of potential covariates was assessed by meta-regression. RESULTS: Data from 53,878 patients enrolled in 30 published reports were collated, including 18 randomized controlled trials (n = 11,253) and 12 observational studies (n = 42,625). In the randomized controlled trials, exercise tolerance was improved by combined therapy (n = 183; weighted MD = 51.5; 95% CI: 27.3 to 75.7; p < 0.001), whereas E/A ratio was not (n = 472; weighted MD = -0.01, 95% CI: -0.02 to 0.02; p = 0.54) even after accounting for baseline E/A (p = 0.87). Over a mean follow-up of 18.6 months, all-cause mortality was not improved by therapy in randomized controlled trials (RR: 0.99, 95% CI: 0.92 to 1.06; p = 0.70), despite accounting for baseline ejection fraction (p = 0.72). In observational reports, there was a reduction in all-cause mortality with therapy in the unadjusted analyses (RR: 0.80, 95% CI: 0.66 to 0.97; p = 0.27), but not after adjustment for clinical and demographic data (RR: 0.93, 95% CI: 0.84 to 1.02; p = 0.10). CONCLUSIONS: Pharmacotherapy of heart failure with preserved ejection fraction demonstrates a quantifiable improvement in exercise tolerance but not mortality.

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