Sodium–Glucose Cotransporter-2 Inhibitors in World Health Organization Group 1 Pulmonary Arterial Hypertension: A REVEAL Lite 2–Matched Cohort With Time-Varying Exposure Analysis

Sodium–glucose cotransporter-2 inhibitors (SGLT2i) improve outcomes across several cardiometabolic conditions, but their role in World Health Organization group 1 pulmonary arterial hypertension (PAH) remains uncertain. We conducted a retrospective, single-center cohort study of adults with group 1 PAH. Patients prescribed SGLT2i were compared with patients without exposure. Propensity-score matching was performed 1:2 using age, sex, baseline REVEAL Lite 2 risk category, diabetes mellitus, and statin use. The primary outcome was all-cause mortality, and the secondary outcome was major adverse cardiovascular events. Associations were evaluated using fixed-exposure and start–stop time-varying Cox models. The matched cohort included 366 patients: 122 (33%) receiving SGLT2i and 244 (67%) controls. Most patients were classified as high risk by REVEAL Lite 2 (106 SGLT2i recipients (87%) and 215 controls (88%), respectively). In the fixed-exposure analysis, SGLT2i use was associated with lower mortality (hazard ratio [HR], 0.53; 95% CI, 0.31-0.91; P =.018), without a significant difference in major adverse cardiovascular events (HR, 1.23; 95% CI, 0.93-1.63; P =.14). In the time-varying analysis, SGLT2i exposure was not significantly associated with mortality (HR, 0.74; 95% CI, 0.26-2.11; P =.57). The apparent survival association was attenuated after accounting for treatment timing, demonstrating the sensitivity of observational PAH estimates to exposure classification and supporting prospective randomized trials.