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


Journal

The American journal of medicine
ISSN: 1555-7162
Titre abrégé: Am J Med
Pays: United States
ID NLM: 0267200

Informations de publication

Date de publication:
06 2020
Historique:
received: 18 10 2019
revised: 02 11 2019
accepted: 03 11 2019
pubmed: 17 3 2020
medline: 15 8 2020
entrez: 17 3 2020
Statut: ppublish

Résumé

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. 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. 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). 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.

Sections du résumé

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.

Identifiants

pubmed: 32173347
pii: S0002-9343(19)31091-5
doi: 10.1016/j.amjmed.2019.11.015
pii:
doi:

Substances chimiques

Adrenergic beta-Antagonists 0
Angiotensin Receptor Antagonists 0
Angiotensin-Converting Enzyme Inhibitors 0
Cardiovascular Agents 0
Mineralocorticoid Receptor Antagonists 0
Ivabradine 3H48L0LPZQ

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

e280-e289

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Morten Rix Hansen (MR)

Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark; Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark; Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark. Electronic address: mrix@health.sdu.dk.

Asbjørn Hróbjartsson (A)

Center for Evidence-Based Medicine, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Odense Explorative Patient Data Network (OPEN), Odense University Hospital, Odense, Denmark.

Lars Videbæk (L)

Department of Cardiology, Odense University Hospital, Odense, Denmark.

Zandra Nymand Ennis (ZN)

Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.

Manan Pareek (M)

Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark; Department of Cardiology, North Zealand Hospital, Hillerød, Denmark; Department of Internal Medicine, Yale New Haven Hospital, New Haven, Conn.

Niels Herluf Paulsen (NH)

Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.

Martin Broe (M)

Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.

Morten Olesen (M)

Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.

Anton Pottegård (A)

Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.

Per Damkier (P)

Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

Jesper Hallas (J)

Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark; Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.

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