Association Between Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitor Use and All-Cause Mortality in Patients With...

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce mortality in heart failure patients with reduced and preserved ejection fraction. Their potential benefits in pulmonary arterial hypertension (PAH) are unknown. This study evaluates the relationship between SGLT2i use and all-cause mortality in patients with PAH.

Using the TriNetX Research Network, we included patients diagnosed with PAH after January 1, 2013. Group A (SGLT2i group) included patients prescribed canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin, and Group B (non-SGLT2i group) included patients not using these medications. Outcomes were assessed at one-, three-, and five-year intervals following the index event (PAH diagnosis and medication initiation). Propensity score matching was used to account for demographics and comorbidities. Matched cohorts included 7,998 patients in Group A and 8,006 in Group B.

Over one year, mortality occurred in 614 of 7,998 patients (7.7%) in Group A, whereas Group B experienced 1,251 deaths among 8,006 patients (15.6%), yielding a risk difference of 7.9% (p < 0.0001). This mortality advantage associated with SGLT2i inhibitor use remained evident at the three-year mark, with 1,012 of 7,998 patients (12.7%) deceased in Group A compared to 1,930 of 8,006 (24.1%) in Group B, translating to an 11.5% absolute risk difference (p < 0.0001). By five years, mortality had reached 1,139 out of 7,998 patients (14.2%) in Group A and 2,190 out of 8,006 (27.4%) in Group B, with a corresponding risk difference of 13.1% (p < 0.0001).

SGLT2i use was associated with significant and sustained mortality reduction in PAH patients. A 13% absolute risk reduction at five years highlights the potential for a transformative impact on PAH management. Randomized controlled trials are warranted to confirm these findings and guide clinical practice.