Identifying optimal doses of heart failure medications in men compared with women: a prospective, observational, cohort study.
Journal
Lancet (London, England)
ISSN: 1474-547X
Titre abrégé: Lancet
Pays: England
ID NLM: 2985213R
Informations de publication
Date de publication:
05 10 2019
05 10 2019
Historique:
received:
19
03
2019
revised:
17
06
2019
accepted:
19
06
2019
pubmed:
27
8
2019
medline:
24
10
2019
entrez:
27
8
2019
Statut:
ppublish
Résumé
Guideline-recommended doses of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), and β blockers are similar for men and women with heart failure with reduced ejection fraction (HFrEF), even though there are known sex differences in pharmacokinetics of these drugs. We hypothesised that there might be sex differences in the optimal dose of ACE inhibitors or ARBs and β blockers in patients with HFrEF. We did a post-hoc analysis of BIOSTAT-CHF, a prospective study in 11 European countries of patients with heart failure in whom initiation and up-titration of ACE inhibitors or ARBs and β blockers was encouraged by protocol. We included only patients with left ventricular ejection fraction less than 40%, and excluded those who died within the first 3 months. Primary outcome was a composite of time to all-cause mortality or hospitalisation for heart failure. Findings were validated in ASIAN-HF, an independent cohort of 3539 men and 961 women with HFrEF. Among 1308 men and 402 women with HFrEF from BIOSTAT-CHF, women were older (74 [12] years vs 70 [12] years, p<0·0001) and had lower bodyweights (72 [16] kg vs 85 [18] kg, p<0·0001) and heights (162 [7] cm vs 174 [8] cm, p<0·0001) than did men, although body-mass index did not differ significantly. A similar number of men and women reached guideline-recommended target doses of ACE inhibitors or ARBs (99 [25%] vs 304 [23%], p=0·61) and β blockers (57 [14%] vs 168 [13%], p=0·54). In men, the lowest hazards of death or hospitalisation for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and β blockers, but women showed approximately 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels. These sex differences were still present after adjusting for clinical covariates, including age and body surface area. In the ASIAN-HF registry, similar patterns were observed for both ACE inhibitors or ARBs and β blockers, with women having approximately 30% lower risk at 50% of the recommended doses, with no further benefit at higher dose levels. This study suggests that women with HFrEF might need lower doses of ACE inhibitors or ARBs and β blockers than men, and brings into question what the true optimal medical therapy is for women versus men. European Commission.
Sections du résumé
BACKGROUND
Guideline-recommended doses of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), and β blockers are similar for men and women with heart failure with reduced ejection fraction (HFrEF), even though there are known sex differences in pharmacokinetics of these drugs. We hypothesised that there might be sex differences in the optimal dose of ACE inhibitors or ARBs and β blockers in patients with HFrEF.
METHODS
We did a post-hoc analysis of BIOSTAT-CHF, a prospective study in 11 European countries of patients with heart failure in whom initiation and up-titration of ACE inhibitors or ARBs and β blockers was encouraged by protocol. We included only patients with left ventricular ejection fraction less than 40%, and excluded those who died within the first 3 months. Primary outcome was a composite of time to all-cause mortality or hospitalisation for heart failure. Findings were validated in ASIAN-HF, an independent cohort of 3539 men and 961 women with HFrEF.
FINDINGS
Among 1308 men and 402 women with HFrEF from BIOSTAT-CHF, women were older (74 [12] years vs 70 [12] years, p<0·0001) and had lower bodyweights (72 [16] kg vs 85 [18] kg, p<0·0001) and heights (162 [7] cm vs 174 [8] cm, p<0·0001) than did men, although body-mass index did not differ significantly. A similar number of men and women reached guideline-recommended target doses of ACE inhibitors or ARBs (99 [25%] vs 304 [23%], p=0·61) and β blockers (57 [14%] vs 168 [13%], p=0·54). In men, the lowest hazards of death or hospitalisation for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and β blockers, but women showed approximately 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels. These sex differences were still present after adjusting for clinical covariates, including age and body surface area. In the ASIAN-HF registry, similar patterns were observed for both ACE inhibitors or ARBs and β blockers, with women having approximately 30% lower risk at 50% of the recommended doses, with no further benefit at higher dose levels.
INTERPRETATION
This study suggests that women with HFrEF might need lower doses of ACE inhibitors or ARBs and β blockers than men, and brings into question what the true optimal medical therapy is for women versus men.
FUNDING
European Commission.
Identifiants
pubmed: 31447116
pii: S0140-6736(19)31792-1
doi: 10.1016/S0140-6736(19)31792-1
pii:
doi:
Substances chimiques
Adrenergic beta-Antagonists
0
Angiotensin Receptor Antagonists
0
Angiotensin-Converting Enzyme Inhibitors
0
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
1254-1263Investigateurs
Arthur Mark Richards
(AM)
Carolyn S P Lam
(CSP)
Inder Anand
(I)
Chung-Lieh Hung
(CL)
Lieng Hsi Ling
(LH)
Houng Bang Liew
(HB)
Calambur Narasimhan
(C)
Tachapong Ngarmukos
(T)
Sang Weon Park
(SW)
Eugenio Reyes
(E)
Bambang Budi Siswanto
(BB)
Wataru Shimizu
(W)
Shu Zhang
(S)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.