Consistent benefit of SGLT2 inhibitors on CV outcomes across various patient populations
Effect of SGLT2 Inhibitors on Cardiovascular Outcomes Across Various Patient Populations
Literature - Usman MS, Siddiqi TJ, Anker SD, et al. - J Am Coll Cardiol. 2023 Jun 27;81(25):2377-2387. doi: 10.1016/j.jacc.2023.04.034Introduction and methods
Background
SGLT2 inhibitors have been studied in various large-scale clinical trials in patients with T2D, HF and CKD [1-12]. The effects of SGLT2 inhibitors on HF outcomes and CV mortality in patient populations with multiple comorbidities of T2D, HF and CKD remain uncertain.
Aim of the study
The authors investigated the effect of SGLT2 inhibitors on CV outcomes in subgroups of patients with various combinations of cardiovascular, kidney, and metabolic comorbidity.
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Methods
A systematic review was performed of literature published in Medline, Scopus and Cochrane Central databases up to the last week of November 2022. In this meta-analysis, primary or secondary analyses of placebo-controlled RCTs with SGLT2 inhibitors were included when they had at least 1000 participants and were reporting on the composite of first HF hospitalization or CV mortality, first HF hospitalization, or CV mortality. A total of 13 studies (n=90,413 participants) were included. Data were analyzed in 12 different patients populations with different combinations of HF, T2D, and CKD.
Main results
Composite of first HF hospitalization or CV mortality
- SGLT2 inhibitors reduced the risk of the composite of first HF hospitalization or CV mortality in patients with HF (HR: 0.76; 95%CI: 0.72-0.81; P<0.001), T2D (HR: 0.77; 95%CI: 0.73-0.81; P<0.001), and CKD (HR: 0.77; 95%CI: 0.71-0.82; P<0.001).
- Consistent benefit of SGLT2 inhibitors on the composite endpoint was observed across various patient populations, including in patients with HFrEF or HFpEF, HF with or without T2D, HF with or without CKD, T2D without HF, T2D with or without CKD, CKD without HF, CKD without T2D, and with all 3 comorbidities. In contrast, SGLT2 inhibitors did not have an effect on the composite outcome in patients with CKD without T2D (HR: 0.95; 95%CI: 0.65-1.40; P=0.51).
First HF hospitalization
- SGLT2 inhibitors reduced the risk of first HF hospitalization in patients with HF (HR: 0.71; 95%CI: 0.67-0.77; P<0.001), T2D (HR: 0.71; 95%CI: 0.66-0.76; P<0.001), and CKD (HR: 0.68; 95%CI: 0.60-0.77; P<0.001).
- The effects on first HF hospitalization were consistent across other patient populations, with the exception of the patient group with all 3 comorbidities which included data of only 1 trial (HR: 0.76; 95%CI: 0.48-1.29; P=0.24). No data was available for patients with CKD without T2D.
CV mortality
- SGLT2 inhibitors reduced CV mortality in patients with HF (HR: 0.85; 95%CI: 0.78-0.92; P<0.001), T2D (HR: 0.85; 95%CI: 0.79-0.91; P<0.001), and CKD (HR: 0.88; 95%CI: 0.81-0.95; P<0.001). Similar findings were reported in patients with HFrEF, HF with or without T2D, HF without CKD, and T2D with CKD.
- A trend towards clinical benefit of SGLT2 inhibitors on CV mortality, albeit not statistically significant, was detected in patients with HF with CKD, T2D without HF, and T2D without CKD.
- SGLT2 inhibitors did not have effect on CV mortality in patients with HFpEF (HR: 0.96; 95%CI: 0.82-1.13; P=0.65), and CKD without T2D (HR: 1.02; 95%CI: 0.44-2.37; P=0.14). No data was available for patients with CKD without HF, and for patients with all 3 comorbidities.
Conclusion
This meta-analysis demonstrated that SGLT2 inhibitors reduce the risk of the composite of HF hospitalizations or CV mortality in patients with HF, T2D, or CKD, and with varying combinations of HF, T2D and CKD. Consistent findings were observed when analyzing first HF hospitalization and CV mortality separately, but the effect of SGLT2 inhibitors on CV mortality was more modest. “These findings support a “call to action” for the widespread adoption of the use of SGLT2 inhibitors across all 3 patient populations.’’, according to the authors.
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