Tang Jia, Wang Ping, Liu Chenxi, Peng Jia, Liu Yubo, Ma Qilin
Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan 410008, China.
Chin Med J (Engl). 2025 Apr 20;138(8):925-933. doi: 10.1097/CM9.0000000000003118. Epub 2024 May 28.
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.
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).
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.
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.
PROSPERO; No. CRD42022354792.
血管紧张素受体脑啡肽酶抑制剂（ARNI）、血管紧张素转换酶抑制剂（ACEI）、血管紧张素受体阻滞剂（ARB）、β受体阻滞剂（BB）和盐皮质激素受体拮抗剂（MRA）是治疗射血分数降低的心力衰竭（HFrEF）的基石。钠-葡萄糖协同转运蛋白2抑制剂（SGLT-2i）也被纳入HFrEF治疗指南。然而，SGLT-2i与这五种药物对HFrEF的影响尚未得到系统评估。
检索PubMed、Embase和Cochrane图书馆，查找从起始日期至2022年9月23日的随机对照试验（RCT）。还纳入了先前相关综述和参考文献中的其他试验。主要结局指标为左心室射血分数（LVEF）、左心室舒张末期内径/尺寸（LVEDD）、左心室收缩末期内径/尺寸（LVESD）、左心室舒张末期容积（LVEDV）、左心室收缩末期容积（LVESV）、左心室收缩末期容积指数（LVESVI）和左心室舒张末期容积指数（LVEDVI）的变化。次要结局指标为纽约心脏协会（NYHA）分级、6分钟步行距离（6MWD）、B型利钠肽（BNP）水平和N末端B型利钠肽原（NT-proBNP）水平。效应量以95%置信区间（CI）的平均差（MD）表示。
我们纳入了68项RCT，涉及16425例患者。与安慰剂相比，ARNI + BB + MRA + SGLT-2i是改善LVEF最有效的联合用药（15.63%，95%CI：9.91%至21.68%）。ARNI + BB + MRA + SGLT-2i（5.83%，95%CI：0.53%至11.14%）和ARNI + BB + MRA（3.83%，95%CI：0.72%至6.90%）在改善LVEF方面优于传统金三角ACEI + BB + MRA。ACEI + BB + MRA + SGLT-2i在改善LVEDVI方面优于ACEI + BB + MRA（-8.05 mL/m²，95%CI：-14.88至-1.23 mL/m²）和ACEI + BB + SGLT-2i（-18.94 mL/m²，95%CI：-36.97至-0.61 mL/m²）。ACEI + BB + MRA + SGLT-2i（-3254.21 pg/mL，95%CI：-6242.19至-560.47 pg/mL）在降低NT-proBNP方面优于ARB + BB + MRA。
在ARNI/ACEI + BB + MRA中添加SGLT-2i有利于逆转心脏重塑。新的四联药物“ARNI + BB + MRA + SGLT-2i”在改善LVEF方面优于金三角“ACEI + BB + MRA”。
PROSPERO；注册号CRD42022354792。
