Postponement of Death by Pharmacological Heart Failure Treatment: A Meta-Analysis of Randomized Clinical Trials

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  • Morten Rix Hansen
  • Asbjørn Hróbjartsson, Odense University Hospital, University of Southern Denmark, Odense
  • ,
  • Lars Videbæk, Odense University Hospital
  • ,
  • Zandra Nymand Ennis, University of Southern Denmark, Odense
  • ,
  • Manan Pareek
  • Niels Herluf Paulsen, University of Southern Denmark, Odense
  • ,
  • Martin Broe, University of Southern Denmark, Odense
  • ,
  • Morten Olesen, University of Southern Denmark, Odense
  • ,
  • Anton Pottegård, University of Southern Denmark, Odense
  • ,
  • Per Damkier, University of Southern Denmark, Odense
  • ,
  • Jesper Hallas, University of Southern Denmark, Odense

Background: Outcome postponement has been proposed as an effect measure for preventive drug treatment. It describes the average delay of the investigated unwanted clinical event, achieved by taking medication. The objective was to estimate postponement of death for the following heart failure medications compared to placebo: beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), ARB added to ACE inhibitors, aldosterone antagonists, ivabradine, and renin antagonists. Methods: We searched Medline and Embase from inception of databases until October 2017. Eligibility criteria were randomized placebo-controlled heart failure trials, including at least 1000 participants, with survival as a prespecified outcome and a minimum trial duration of 1 year. We calculated the outcome postponement by modeling the area between survival curves. This area was modeled on the basis of the hazard ratio or relative risk, the rate of mortality in the placebo group, and the trial duration. All results were standardized to a 3-year trial duration to ensure comparability between treatments. Results: We identified 14 eligible trials, with a total of 52,014 patients. The results in terms of postponement of all-cause mortality was: beta-blockers 43.7 days (95% confidence interval [95% CI], 20.8-66.5), ACE inhibitors 41.0 days (95% CI, 18.8-63.3), and aldosterone-antagonists 41.3 days (95% CI, 14.3,68.4). Conclusion: The modeled outcome postponement estimates reiterate beta-blockers, ACE inhibitors, and aldosterone antagonists as the mainstay of heart failure treatment. Furthermore, ivabradine or ARBs added to ACE inhibitors results in no statistically significant gain in survival.

Original languageEnglish
JournalAmerican Journal of Medicine
Volume133
Issue6
Pages (from-to)e280-e289
Number of pages10
ISSN0002-9343
DOIs
Publication statusPublished - Jun 2020

    Research areas

  • Effect measure, Heart failure, Meta-analysis, Outcome postponement, Randomized Controlled Trial

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