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
- 1Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ
Abstract
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.
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BibTeX
@article{abdelrahmanhafez2026sodiumglucose,
title = {{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}},
author = {Abdelrahman Hafez, MD and Amal Youssef, MD and Mohamed Nour, MD and Juan M. Farina, MD and Kamal Awad, MD and Milagros Pereyra Pietri, MD and Isabel G. Scalia, MD and Fatmaelzahraa Abdelfattah, MD and Mahshad Razaghi, MD and Laurève Chollet, MD and Sherif Ahmed, MD and Ramzi Ibrahim, MD and Nikita Rafie, MD and Robert L. Scott, MD, PhD and Chadi Ayoub, MBBS, PhD and Reza Arsanjani, MD},
journal = {Mayo Clinic Proceedings: Innovations, Quality \& Outcomes},
year = {2026},
month = oct,
doi = {10.1016/j.mayocpiqo.2026.100765},
url = {https://doi.org/10.1016/j.mayocpiqo.2026.100765},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - 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
AU - Abdelrahman Hafez, MD
AU - Amal Youssef, MD
AU - Mohamed Nour, MD
AU - Juan M. Farina, MD
AU - Kamal Awad, MD
AU - Milagros Pereyra Pietri, MD
AU - Isabel G. Scalia, MD
AU - Fatmaelzahraa Abdelfattah, MD
AU - Mahshad Razaghi, MD
AU - Laurève Chollet, MD
AU - Sherif Ahmed, MD
AU - Ramzi Ibrahim, MD
AU - Nikita Rafie, MD
AU - Robert L. Scott, MD, PhD
AU - Chadi Ayoub, MBBS, PhD
AU - Reza Arsanjani, MD
PY - 2026
DA - 2026/10/21
JO - Mayo Clinic Proceedings: Innovations, Quality & Outcomes
DO - 10.1016/j.mayocpiqo.2026.100765
UR - https://doi.org/10.1016/j.mayocpiqo.2026.100765
AB - 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.
SN - 2542-4548
ER -