AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
SGLT2 Inhibitors in WHO Group 1 Pulmonary Arterial Hypertension: A REVEAL Lite 2-Matched Cohort with Time-Varying Exposure Analysis
By Hafez A, Youssef A, Awad K et al.
Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve cardio-renal outcomes in broad cardiometabolic populations, but their role in WHO Group 1 pulmonary arterial hypertension (PAH) remains uncertain. We evaluated the association between SGLT2i exposure and outcomes in adults with WHO Group 1 PAH using REVEAL Lite 2 (RL2)-anchored matching and time-varying exposure modeling. Methods: We conducted a retrospective cohort study of adults with WHO Group 1 PAH at a tertiary center. Patients prescribed SGLT2i, including empagliflozin, dapagliflozin, canagliflozin, or ertugliflozin, were compared with PAH controls without SGLT2i exposure. Propensity score matching was performed 1:2 using age, sex, baseline RL2 risk category, diabetes mellitus, and statin use. The primary outcome was all-cause mortality. The secondary outcome was major adverse cardiovascular events (MACE), defined as nonfatal myocardial infarction, stroke, cardiovascular death, urgent coronary revascularization, or acute heart failure hospitalization. Associations were assessed using both conventional fixed-exposure Cox models and start-stop time-varying Cox models. Results: The matched cohort included 366 patients: 122 SGLT2i-exposed patients and 244 controls. In the fixed-exposure Cox model, SGLT2i use was associated with lower all-cause mortality (hazard ratio [HR], 0.53; 95% CI, 0.31-0.91; P=0.018), Fig.1 while MACE did not differ significantly (HR, 1.23; 95% CI, 0.93-1.63; P=0.14). However, when SGLT2i exposure was modeled as time-varying, the mortality association attenuated and was no longer statistically significant (HR, 0.74; 95% CI, 0.26-2.11; P=0.57). Conclusion: In an RL2-matched WHO Group 1 PAH cohort, SGLT2i exposure was not significantly associated with mortality after accounting for post-diagnosis treatment initiation. These findings highlight the importance of time-varying methods in PAH pharmacoepidemiology and support prospective PAH-focused trials.