Dapagliflozin in Heart Failure: A Comprehensive Meta-analysis on Functional Capacity, Symptoms, and Safety Outcomes

Objective

To evaluate the comparative effects of dapagliflozin versus placebo in patients with heart failure (HF), focusing on functional capacity, symptoms, and safety outcomes.

Background

Despite advancements in heart failure (HF) therapy, HF is still a significant cause of recurrent hospitalization and death worldwide. Dapagliflozin has demonstrated potential in lowering hospitalizations and mortality associated with heart failure; however, its impact on functional capacity, particularly the 6-min walk distance (6MWD), and the comprehensive assessment of safety outcomes in diverse HF populations, including those with preserved or reduced ejection fraction (HFpEF and HFrEF, respectively), requires further investigation.

Methods

PubMed, Web of Science, Cochrane Library, and Scopus databases were comprehensively searched to identify randomized controlled trials (RCTs) investigating the efficacy of dapagliflozin in comparison with control interventions for heart failure. The primary outcome was a change in the 6MWD, KCCQ score, and safety measures included hospitalization, all-cause mortality, and adverse events.

Results

In our meta-analysis of ten studies involving 12,695 patients with heart failure, dapagliflozin showed significantly improved Kansas City Cardiomyopathy Questionnaire (KCCQ) scores [risk ratio (RR) of 2.75, 95% confidence interval (CI) (1.95–3.569), p < 0.00001] and no significant differences in 6-min walk distance [6MWD; RR of 3.59, 95% CI (− 1.44 to 8.63), p = 0.16]. Dapagliflozin demonstrated a notable reduction in hospitalization for heart failure [RR of 0.76, 95% CI (0.68–0.84), p < 0.00001], significant overall reduction on the effect of any cause mortality [RR of 0.90, 95% CI (0.83–0.99), p = 0.03). There was, however, no significant effect on adverse events [RR of 0.96, 95% CI (0.98–1.03), p = 0.39).

Conclusions

Our meta-analysis of ten trials concluded that dapagliflozin significantly improved KCCQ scores in both HFrEF and HFpEF. The improvement in 6MWD was not statistically significant but trended toward dapagliflozin. Dapagliflozin also showed a mortality benefit in patients with reduced ejection fraction; however, in patients with preserved ejection fraction, the result was not statistically significant. There was also a statistically significant reduction in heart failure hospitalizations across all classes.