Abstract 4139853: Altering Cardiovascular Mortality in HFpEF with SGLT2i or ARNI — A Head-to-Head Analysis

Background: Therapeutic options for HFpEF are continuously evolving. The latest AHA guidelines recommend ARNI with a class 2B and SGLT2i with a class 2A for HFpEF. Trials indicate that both SGLT2i and ARNI can improve clinical outcomes, but the practical implications of these costly novel agents must be considered. In this study, we assessed the effects of ARNI and SGLT2 inhibitors on cardiovascular mortality in HFpEF patients. Methods: PubMed, Scopus, and Cochrane search identified RCTs comparing ARNI with Valsartan, ACEi, or placebo, and SGLT2i with placebo. The outcome was cardiovascular mortality, comparing ARNI and SGLT2i subgroups. Heterogeneity was assessed with I^2 statistics with a random-effects model. Results: We included 8 RCTs with 15212 patients. Four studies were included with 27.6% being females with an age range of 70.9 - 72.9 years. Follow-up ranged from 8 weeks to 41 months, and mean LVEF was 57.3 ± 8%. Pooled RR for cardiovascular mortality (0.71 [95% CI: 0.47-1.09], P = 0.11) indicated no significant reduction in risk, with moderate heterogeneity (I^2 = 48%, P = 0.12) In four studies in the SGLT2i subgroup, the age range was 60 to 71.9 years, with an LVEF range of 45 - 61%, and 48.7% of the participants were female. One study found women were more likely to have EF >60% than EF ≤45%. Background medication of ARNI or RAAS inhibitors was continued. Follow-up time ranged from 26.2 months to 4.2 years. Pooled RR for cardiovascular mortality (0.94 [95% CI: 0.83-1.06], P = 0.30) showed no significant reduction in risk, with low heterogeneity (I^2 = 34%, P = 0.21) Combining both ARNI and SGLT2i groups, the total number of patients was 15,212 for the treatment group and 12,426 for the control group. The overall pooled RR (0.91 [95% CI: 0.81-1.03], P = 0.13) suggested no significant difference in cardiovascular mortality, with low heterogeneity across all studies (I^2= 34%, P = 0.16) The test for subgroup differences between ARNI and SGLT2i was not significant (P = 0.22) with low heterogeneity (I^2 = 33.4%) Conclusion: In HFpEF, subgroup analysis showed no significant differences in cardiovascular mortality reduction between ARNI and SGLT2i. Further research should investigate additional clinical and functional endpoints, considering the cost-effectiveness of these treatments.