title: Effects of treatment on exercise tolerance, cardiac function, and mortality in heart failure with preserved ejection fraction. A meta-analysis.
abstract: OBJECTIVE
  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.
authors.affiliation: School of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Holland
authors.forename: Dharam J
authors.initials: DJ
authors.lastname: Kumbhani
authors.forename: Salim H
authors.initials: SH
authors.lastname: Ahmed
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Marwick
mesh_terms: D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D017079:Exercise Tolerance / Q000187:drug effects / Q000502:physiology*; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome
chemical_list: D002317:Cardiovascular Agents