Pharmacotherapy in patients with heart failure with reduced ejection fraction: A systematic review and meta-analysis.
10.1097/CM9.0000000000003118
- Author:
Jia TANG
1
;
Ping WANG
1
;
Chenxi LIU
1
;
Jia PENG
1
;
Yubo LIU
1
;
Qilin MA
1
Author Information
1. Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
- Publication Type:Network Meta-Analysis
- Keywords:
Cardiac reverse remodeling;
Drug combinations;
Heart failure;
Network meta-analysis
- MeSH:
Humans;
Heart Failure/physiopathology*;
Stroke Volume/physiology*;
Angiotensin Receptor Antagonists/therapeutic use*;
Angiotensin-Converting Enzyme Inhibitors/therapeutic use*;
Sodium-Glucose Transporter 2 Inhibitors/therapeutic use*;
Randomized Controlled Trials as Topic;
Mineralocorticoid Receptor Antagonists/therapeutic use*;
Adrenergic beta-Antagonists/therapeutic use*
- From:
Chinese Medical Journal
2025;138(8):925-933
- CountryChina
- Language:English
-
Abstract:
BACKGROUND:Angiotensin receptor neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) are the cornerstones in treating heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are included in HFrEF treatment guidelines. However, the effect of SGLT-2i and the five drugs on HFrEF have not yet been systematically evaluated.
METHODS:PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) from inception dates to September 23, 2022. Additional trials from previous relevant reviews and references were also included. The primary outcomes were changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter/dimension (LVEDD), left ventricular end-systolic diameter/dimension (LVESD), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI). Secondary outcomes were New York Heart Association (NYHA) class, 6-min walking distance (6MWD), B-type natriuretic peptide (BNP) level, and N-terminal pro-BNP (NT-proBNP) level. The effect sizes were presented as the mean difference (MD) with 95% confidence interval (CI).
RESULTS:We included 68 RCTs involving 16,425 patients. Compared with placebo, ARNI + BB + MRA + SGLT-2i was the most effective combination to improve LVEF (15.63%, 95% CI: 9.91% to 21.68%). ARNI + BB + MRA + SGLT-2i (5.83%, 95% CI: 0.53% to 11.14%) and ARNI + BB + MRA (3.83%, 95% CI: 0.72% to 6.90%) were superior to the traditional golden triangle ACEI + BB + MRA in improving LVEF. ACEI + BB + MRA + SGLT-2i was better than ACEI + BB + MRA (-8.05 mL/m 2 , 95% CI: -14.88 to -1.23 mL/m 2 ) and ACEI + BB + SGLT-2i (-18.94 mL/m 2 , 95% CI: -36.97 to -0.61 mL/m 2 ) in improving LVEDVI. ACEI + BB + MRA + SGLT-2i (-3254.21 pg/mL, 95% CI: -6242.19 to -560.47 pg/mL) was superior to ARB + BB + MRA in reducing NT-proBNP.
CONCLUSIONS:Adding SGLT-2i to ARNI/ACEI + BB + MRA is beneficial for reversing cardiac remodeling. The new quadruple drug "ARNI + BB + MRA + SGLT-2i" is superior to the golden triangle "ACEI + BB + MRA" in improving LVEF.
REGISTRATION:PROSPERO; No. CRD42022354792.
