Author + information
- Received September 4, 2010
- Revision received October 19, 2010
- Accepted October 28, 2010
- Published online April 19, 2011.
- David J. Holland, BScApp⁎,
- Dharam J. Kumbhani, MD, SM†,
- Salim H. Ahmed, MD† and
- Thomas H. Marwick, MBBS, PhD†,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Thomas H. Marwick, Cardiovascular Medicine J1-5, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195
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.
Continuing Medical Education (CME) is available for this article.
The authors have reported that they have no relationships to disclose.
- Received September 4, 2010.
- Revision received October 19, 2010.
- Accepted October 28, 2010.
- American College of Cardiology Foundation