{"title":"SGLT2i联合ARNi与RASi治疗心力衰竭伴射血分数降低：在现实世界队列研究中提高生存率和降低高钾血症风险","authors":"Jian-Rong Peng, Tien-Hsing Chen, Dong-Yi Chen, Yuan Lin, Tien-Shin Chou, Ning-I Yang, Chao-Yung Wang, Ming-Lung Tsai","doi":"10.1016/j.jjcc.2025.09.002","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The management of heart failure with reduced ejection fraction (HFrEF) has advanced with the introduction of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and angiotensin receptor-neprilysin inhibitors (ARNi). However, direct comparisons between combination therapies using SGLT2i plus ARNi versus SGLT2i plus conventional renin-angiotensin system inhibitors (RASi) remain limited.</p><p><strong>Methods: </strong>This retrospective cohort study included 2985 HFrEF patients receiving SGLT2i with either ARNi (n = 1542) or RASi (n = 1443) between 2016 and 2022. Inverse probability of treatment weighting was applied to balance baseline characteristics. The primary outcomes included all-cause mortality, cardiovascular death, heart failure hospitalization (HFH), and renal function decline.</p><p><strong>Results: </strong>Over a median follow-up of 1.1 years, SGLT2i + ARNi was associated with significantly lower all-cause mortality compared to SGLT2i + RASi [hazard ratio (HR): 0.81; 95 % confidence interval (CI): 0.67-0.97]. Risk of cardiovascular death (HR: 0.95; 95 % CI: 0.85-1.0), HFH (subdistribution HR: 0.95; 95 % CI: 0.85-1.06), and renal function decline (subdistribution HR: 0.96; 95 % CI: 0.82-1.13) were comparable between groups. The incidence of hyperkalemia was significantly lower with SGLT2i + ARNi (subdistribution HR: 0.38; 95 % CI: 0.27-0.54). Subgroup analysis revealed a more pronounced survival benefit of SGLT2i + ARNi among patients without heart failure hospitalization in the prior year (HR = 0.58 vs. 0.87; p for interaction = 0.041).</p><p><strong>Conclusion: </strong>Among patients with HFrEF receiving SGLT2i therapy, concomitant use of ARNi was associated with a significant reduction in all-cause mortality, comparable cardiovascular and renal outcomes, and a lower risk of hyperkalemia compared to RASi. These findings support the preferential use of ARNi over RASi as background therapy in SGLT2i-treated HFrEF patients.</p>","PeriodicalId":15223,"journal":{"name":"Journal of cardiology","volume":" ","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"SGLT2i with ARNi versus RASi in heart failure with reduced ejection fraction: Improved survival and reduced hyperkalemia risk in a real-world cohort study.\",\"authors\":\"Jian-Rong Peng, Tien-Hsing Chen, Dong-Yi Chen, Yuan Lin, Tien-Shin Chou, Ning-I Yang, Chao-Yung Wang, Ming-Lung Tsai\",\"doi\":\"10.1016/j.jjcc.2025.09.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The management of heart failure with reduced ejection fraction (HFrEF) has advanced with the introduction of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and angiotensin receptor-neprilysin inhibitors (ARNi). However, direct comparisons between combination therapies using SGLT2i plus ARNi versus SGLT2i plus conventional renin-angiotensin system inhibitors (RASi) remain limited.</p><p><strong>Methods: </strong>This retrospective cohort study included 2985 HFrEF patients receiving SGLT2i with either ARNi (n = 1542) or RASi (n = 1443) between 2016 and 2022. Inverse probability of treatment weighting was applied to balance baseline characteristics. The primary outcomes included all-cause mortality, cardiovascular death, heart failure hospitalization (HFH), and renal function decline.</p><p><strong>Results: </strong>Over a median follow-up of 1.1 years, SGLT2i + ARNi was associated with significantly lower all-cause mortality compared to SGLT2i + RASi [hazard ratio (HR): 0.81; 95 % confidence interval (CI): 0.67-0.97]. Risk of cardiovascular death (HR: 0.95; 95 % CI: 0.85-1.0), HFH (subdistribution HR: 0.95; 95 % CI: 0.85-1.06), and renal function decline (subdistribution HR: 0.96; 95 % CI: 0.82-1.13) were comparable between groups. The incidence of hyperkalemia was significantly lower with SGLT2i + ARNi (subdistribution HR: 0.38; 95 % CI: 0.27-0.54). Subgroup analysis revealed a more pronounced survival benefit of SGLT2i + ARNi among patients without heart failure hospitalization in the prior year (HR = 0.58 vs. 0.87; p for interaction = 0.041).</p><p><strong>Conclusion: </strong>Among patients with HFrEF receiving SGLT2i therapy, concomitant use of ARNi was associated with a significant reduction in all-cause mortality, comparable cardiovascular and renal outcomes, and a lower risk of hyperkalemia compared to RASi. These findings support the preferential use of ARNi over RASi as background therapy in SGLT2i-treated HFrEF patients.</p>\",\"PeriodicalId\":15223,\"journal\":{\"name\":\"Journal of cardiology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-09-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of cardiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jjcc.2025.09.002\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of cardiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jjcc.2025.09.002","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
SGLT2i with ARNi versus RASi in heart failure with reduced ejection fraction: Improved survival and reduced hyperkalemia risk in a real-world cohort study.
Background: The management of heart failure with reduced ejection fraction (HFrEF) has advanced with the introduction of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and angiotensin receptor-neprilysin inhibitors (ARNi). However, direct comparisons between combination therapies using SGLT2i plus ARNi versus SGLT2i plus conventional renin-angiotensin system inhibitors (RASi) remain limited.
Methods: This retrospective cohort study included 2985 HFrEF patients receiving SGLT2i with either ARNi (n = 1542) or RASi (n = 1443) between 2016 and 2022. Inverse probability of treatment weighting was applied to balance baseline characteristics. The primary outcomes included all-cause mortality, cardiovascular death, heart failure hospitalization (HFH), and renal function decline.
Results: Over a median follow-up of 1.1 years, SGLT2i + ARNi was associated with significantly lower all-cause mortality compared to SGLT2i + RASi [hazard ratio (HR): 0.81; 95 % confidence interval (CI): 0.67-0.97]. Risk of cardiovascular death (HR: 0.95; 95 % CI: 0.85-1.0), HFH (subdistribution HR: 0.95; 95 % CI: 0.85-1.06), and renal function decline (subdistribution HR: 0.96; 95 % CI: 0.82-1.13) were comparable between groups. The incidence of hyperkalemia was significantly lower with SGLT2i + ARNi (subdistribution HR: 0.38; 95 % CI: 0.27-0.54). Subgroup analysis revealed a more pronounced survival benefit of SGLT2i + ARNi among patients without heart failure hospitalization in the prior year (HR = 0.58 vs. 0.87; p for interaction = 0.041).
Conclusion: Among patients with HFrEF receiving SGLT2i therapy, concomitant use of ARNi was associated with a significant reduction in all-cause mortality, comparable cardiovascular and renal outcomes, and a lower risk of hyperkalemia compared to RASi. These findings support the preferential use of ARNi over RASi as background therapy in SGLT2i-treated HFrEF patients.
期刊介绍：
The official journal of the Japanese College of Cardiology is an international, English language, peer-reviewed journal publishing the latest findings in cardiovascular medicine. Journal of Cardiology (JC) aims to publish the highest-quality material covering original basic and clinical research on all aspects of cardiovascular disease. Topics covered include ischemic heart disease, cardiomyopathy, valvular heart disease, vascular disease, hypertension, arrhythmia, congenital heart disease, pharmacological and non-pharmacological treatment, new diagnostic techniques, and cardiovascular imaging. JC also publishes a selection of review articles, clinical trials, short communications, and important messages and letters to the editor.
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