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

Am J Med. 2020 Jun;133(6):e280-e289. doi: 10.1016/j.amjmed.2019.11.015. Epub 2020 Mar 13.


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.

Keywords: Effect measure; Heart failure; Meta-analysis; Outcome postponement; Randomized Controlled Trial.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use*
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Cardiovascular Agents / therapeutic use*
  • Cause of Death
  • Drug Therapy, Combination
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Humans
  • Ivabradine / therapeutic use*
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Survival Rate*


  • Adrenergic beta-Antagonists
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Cardiovascular Agents
  • Mineralocorticoid Receptor Antagonists
  • Ivabradine