Sex differences in cardiovascular outcomes of SGLT-2 inhibitors in heart failure randomized controlled trials: A systematic review and meta-analysis

Authors

Frederick Berro Rivera, Department of Medicine, Lincoln Medical Center, Bronx, NY, USA.
Vincent Anthony Tang, Department of Medicine, University of the Philippines - Philippine General Hospital, Metro Manila, Philippines.
Deogracias Villa De Luna, Department of Internal Medicine, Danbury Hospital, Danbury, CT, USA.Follow
Edgar V. Lerma, Advocate Aurora Health
Krishnaswami Vijayaraghavan, University of Arizona, AZ, USA.
Amir Kazory, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, Gainesville, FL, USA.
Nilay S. Shah, Department of Medicine (Cardiology), Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Annabelle Santos Volgman, Division of Cardiology, Rush University Medical Center, Chicago, IL, USA.

Recommended Citation

Rivera FB, Tang VAS, De Luna DV, et al. Sex differences in cardiovascular outcomes of SGLT-2 inhibitors in heart failure randomized controlled trials: A systematic review and meta-analysis. Am Heart J Plus. 2023;26:100261. doi:10.1016/j.ahjo.2023.100261

Affiliations

Advocate Christ Medical Center

Abstract

Background: In patients with heart failure (HF), randomized controlled trials (RCTs) of sodium-glucose transporter-2 inhibitors (SGLT-2is) have proven to be effective in decreasing the primary composite outcome of cardiovascular death and hospitalizations for HF. A recently published meta-analysis showed that the use of SGLT-2is among women with diabetes resulted in less reduction in primary composite outcomes compared with men. This study aims to explore potential sex differences in primary composite outcomes among patients with HF treated with SGLT-2is.

Methods: We systematically searched the medical database from 2017 to 2022 and retrieved all the RCTs using SGLT-2is with specified cardiovascular outcomes. We used the PRISMA (Preferred Reporting Items for a Review and Meta-analysis) method to screen for eligibility. We evaluated the quality of studies using the Cochrane Risk of Bias tool. We pooled the hazard ratio (HR) of the primary composite outcomes in both sexes, performed a meta-analysis, and calculated the odds ratio (OR) of the primary composite outcomes based on sex.

Results: We included 5 RCTs with a total number of 21,947 patients. Of these, 7837 (35.7 %) were females. Primary composite outcomes were significantly lower in males and females taking SGLT-2is compared to placebo (males - HR 0.77; 95 % CI 0.72 to 0.84; p = 0.00001; females - HR 0.75; 95 % CI 0.67 to 0.84; p = 0.00001). Pooled data from four of the RCTs ( n = 20,725) revealed a greater occurrence of the primary composite outcomes in females compared with males (OR 1.32; 95 % CI 1.17 to 1.48; p = 0.0002).

Conclusion: SGLT-2is reduce the risk of primary composite outcomes in patients with HF, regardless of sex; however, the benefits were less pronounced in women. Further research needs to be done to better explain these observed differences in outcomes.

Document Type

Article

PubMed ID

37305172