Canagliflozin reduces oral loop diuretic intensification in patients with type 2 diabetes: A participant-level pooled analysis of the CANVAS and CREDENCE trials

IF 10.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS European Journal of Heart Failure Pub Date : 2025-01-23 DOI:10.1002/ejhf.3586

Safia Chatur, Muthiah Vaduganathan, Robert A. Fletcher, Vlado Perkovic, Hiddo Heerspink, Clare Arnott, Carol Pollock, Kenneth W. Mahaffey, Bruce Neal, Meg Jardine, Scott D. Solomon, Brendon L. Neuen

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Abstract

Aims

The sodium–glucose cotransporter 2 inhibitor canagliflozin reduces the risk of heart failure (HF) hospitalization or cardiovascular death and chronic kidney disease (CKD) progression among patients with type 2 diabetes at high cardiovascular risk or with CKD. Patients with type 2 diabetes commonly have coexisting HF or CKD that require treatment with loop diuretics; however, the prognostic implications of oral loop diuretic intensification are not well characterized.

Methods and results

In this participant-level pooled analysis of the CREDENCE and CANVAS trials (not including CANVAS-R), 1454/8731 (16.7%) patients were treated with loop diuretics at baseline. Over a median on-treatment follow-up of 2.2 years, 1264 patients (14.5%) required oral loop diuretic intensification, of whom 981 (77.6%) required initiation of oral loop diuretics and 283 (22.4%) required oral loop diuretic dose increase. Patients requiring oral loop diuretic intensification experienced rates of subsequent HF hospitalization, CKD progression and mortality that were 29.5-, 5.0-, and 3.5-fold higher, respectively, than those not requiring oral loop diuretic intensification. Treatment with canagliflozin reduced the need for oral loop diuretic intensification by 41% (hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.53–0.66) including both new diuretic initiation (HR 0.65; 95% CI 0.57–0.74) and diuretic dose increase (HR 0.42; 95% CI 0.33–0.54). Inclusion of oral diuretic intensification in an expanded HF composite outcome inclusive of cardiovascular death and HF hospitalization approximately double the number of events, with similar observed treatment effect (HR 0.64; 95% CI 0.58–0.70).

Conclusion

Among high-risk patients with type 2 diabetes, new oral loop diuretic intensification was frequent and portended adverse prognostic significance. Treatment with canagliflozin significantly reduced the need for loop diuretic intensification.

Clinical Trial Registration: CANVAS (Canagliflozin Cardiovascular Assessment Study), ClinicalTrials.gov NCT01032629; CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation), ClinicalTrials.gov NCT02065791.

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canag列净降低2型糖尿病患者的口服利尿剂强化：CANVAS和CREDENCE试验的参与者水平汇总分析

钠-葡萄糖共转运蛋白2抑制剂canagliflozin可降低2型糖尿病高危心血管或CKD患者心力衰竭住院或心血管死亡和慢性肾脏疾病进展的风险。2型糖尿病患者通常伴有心衰或慢性肾病，需要循环利尿剂治疗；然而，口服利尿剂强化对预后的影响尚不明确。

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来源期刊

European Journal of Heart Failure 医学-心血管系统

CiteScore

27.30

自引率

11.50%

发文量

365

审稿时长

1 months

期刊介绍： European Journal of Heart Failure is an international journal dedicated to advancing knowledge in the field of heart failure management. The journal publishes reviews and editorials aimed at improving understanding, prevention, investigation, and treatment of heart failure. It covers various disciplines such as molecular and cellular biology, pathology, physiology, electrophysiology, pharmacology, clinical sciences, social sciences, and population sciences. The journal welcomes submissions of manuscripts on basic, clinical, and population sciences, as well as original contributions on nursing, care of the elderly, primary care, health economics, and other related specialist fields. It is published monthly and has a readership that includes cardiologists, emergency room physicians, intensivists, internists, general physicians, cardiac nurses, diabetologists, epidemiologists, basic scientists focusing on cardiovascular research, and those working in rehabilitation. The journal is abstracted and indexed in various databases such as Academic Search, Embase, MEDLINE/PubMed, and Science Citation Index.