PMID- 33766629
OWN - NLM
STAT- MEDLINE
DCOM- 20220209
LR  - 20220209
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 169
DP  - 2021 Jul
TI  - Combination pharmacotherapies for cardiac reverse remodeling in heart failure 
      patients with reduced ejection fraction: A systematic review and network 
      meta-analysis of randomized clinical trials.
PG  - 105573
LID - S1043-6618(21)00157-2 [pii]
LID - 10.1016/j.phrs.2021.105573 [doi]
AB  - Pharmacotherapies, including angiotensin-converting enzyme inhibitors (ACEIs), 
      angiotensin receptor II blockers (ARBs), beta-blockers (BBs), mineralocorticoid 
      receptor antagonists (MRAs) and angiotensin receptor blocker-neprilysin inhibitor 
      (ARNI), have played a pivotal role in reducing in-hospital and mortality in heart 
      failure patients with reduced ejection fraction (HFrEF). However, effects of the 
      five drug categories used alone or in combination for cardiac reverse remodeling 
      (CRR) in these patients have not been systematically evaluated. A Bayesian 
      network meta-analysis was conducted based on 55 randomized controlled trials 
      published between 1989 and 2019 involving 12,727 patients from PubMed, EMBASE, 
      Cochrane Library, and Clinicaltrials.gov. The study is registered with PROSPERO 
      (CRD42020170457). Our primary outcomes were CRR indicators, including changes of 
      left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume 
      (LVEDV) and end-systolic volume (LVESV), indexed LVEDV (LVEDVI) and LVESV 
      (LVESVI), and left ventricular end-diastolic dimension (LVEDD) and end-systolic 
      dimension (LVESD); Secondary outcomes were functional capacity comprising New 
      York Heart Association (NYHA) class and 6-min walking distance (6MWD); cardiac 
      biomarkers involving B type natriuretic peptide (BNP) and N-terminal pro-BNP 
      (NT-proBNP). The effect sizes were presented as the mean difference with 95% 
      credible intervals. According to the results, all dual-combination therapies 
      except ACEI+ARB were significantly more associated with LVEF or NYHA improvement 
      than placebo, ARB+BB and ARNI+BB were the top two effective dual-combinations in 
      LVEF improvement (+7.59% [+4.27, +11.25] and +7.31% [+3.93, +10.97] 
      respectively); ACEI+BB was shown to be superior to ACEI in reducing LVEDVI and 
      LVESVI (-6.88 mL/m(2) [-13.18, -1.89] and -10.64 mL/m(2) [-18.73, -3.54] 
      respectively); ARNI+BB showed superiority over ACEI+BB in decreasing the level of 
      NT-proBNP (-240.11 pg/mL [-456.57, -6.73]). All tri-combinations were 
      significantly more effective than placebo in LVEF improvement, and ARNI+BB+MRA 
      ranked first (+21.13% [+14.34, +28.13]); ACEI+BB+MRA was significantly more 
      associated with a decrease in LVEDD than ACEI (-6.57 mm [-13.10, -0.84]). A 
      sensitivity analysis ignoring concomitant therapies for LVEF illustrated that all 
      the five drug types except ARB were shown to be superior to placebo, and ARNI 
      ranked first (+4.83% [+1.75, +7.99]). In conclusion, combination therapies exert 
      more benefits on CRR for patients with HFrEF. Among them, ARNI+BB, ARB+BB, 
      ARNI+BB+MRA and ARB+BB+MRA were the top two effective dual and triple 
      combinations in LVEF improvement, respectively; The new "Golden Triangle" of 
      ARNI+BB+MRA was shown to be superior to ACEI+BB+MRA or ARB+BB+MRA in LVEF 
      improvement.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Bao, Jieli
AU  - Bao J
AD  - The Institute of Cardiovascular Disease Research, Xuzhou Medical University, 
      Xuzhou, Jiangsu, PR China; The Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou, Jiangsu, PR China.
FAU - Kan, Rongsheng
AU  - Kan R
AD  - The Institute of Cardiovascular Disease Research, Xuzhou Medical University, 
      Xuzhou, Jiangsu, PR China.
FAU - Chen, Junhong
AU  - Chen J
AD  - The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, PR China.
FAU - Xuan, Haochen
AU  - Xuan H
AD  - The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, PR China.
FAU - Wang, Chaofan
AU  - Wang C
AD  - The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, PR China.
FAU - Li, Dongye
AU  - Li D
AD  - The Institute of Cardiovascular Disease Research, Xuzhou Medical University, 
      Xuzhou, Jiangsu, PR China; The Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou, Jiangsu, PR China. Electronic address: Dongyeli@xzhmu.edu.cn.
FAU - Xu, Tongda
AU  - Xu T
AD  - The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, PR China.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Systematic Review
DEP - 20210322
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Cardiotonic Agents)
SB  - IM
MH  - Cardiotonic Agents/administration & dosage/pharmacology/*therapeutic use
MH  - Drug Therapy, Combination
MH  - Heart Failure/*drug therapy/physiopathology
MH  - Humans
MH  - Network Meta-Analysis
MH  - Randomized Controlled Trials as Topic
MH  - Stroke Volume/*drug effects
MH  - Ventricular Remodeling/*drug effects
OTO - NOTNLM
OT  - Bisoprolol (PubChem CID: 2405)
OT  - Cardiac reverse remodeling
OT  - Enalapril (PubChem CID: 5388962)
OT  - Heart failure
OT  - LCZ 696 (PubChem CID: 78070868)
OT  - Network meta-analysis
OT  - Pharmacotherapies
OT  - Spironolactone (PubChem CID: 5833)
OT  - Valsartan (PubChem CID: 60846)
EDAT- 2021/03/27 06:00
MHDA- 2022/02/10 06:00
CRDT- 2021/03/26 06:09
PHST- 2020/12/31 00:00 [received]
PHST- 2021/03/15 00:00 [revised]
PHST- 2021/03/18 00:00 [accepted]
PHST- 2021/03/27 06:00 [pubmed]
PHST- 2022/02/10 06:00 [medline]
PHST- 2021/03/26 06:09 [entrez]
AID - S1043-6618(21)00157-2 [pii]
AID - 10.1016/j.phrs.2021.105573 [doi]
PST - ppublish
SO  - Pharmacol Res. 2021 Jul;169:105573. doi: 10.1016/j.phrs.2021.105573. Epub 2021 
      Mar 22.