Lemonjava Irakli, Gudushauri Nino, Tskhakaia Irakli, Manzano Jose M, Subramanian Apoorva, Lo Kevin B, Azmaiparashvili Zurab
Internal Medicine, Einstein Medical Center Philadelphia, Philadelphia, USA.
Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
Cureus. 2025 Aug 6;17(8):e89465. doi: 10.7759/cureus.89465. eCollection 2025 Aug.
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.
钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）可降低射血分数降低和保留的心力衰竭患者的死亡率。它们在肺动脉高压（PAH）中的潜在益处尚不清楚。本研究评估了PAH患者使用SGLT2i与全因死亡率之间的关系。
利用TriNetX研究网络，我们纳入了2013年1月1日之后被诊断为PAH的患者。A组（SGLT2i组）包括开具卡格列净、达格列净、恩格列净或依鲁格列净的患者，B组（非SGLT2i组）包括未使用这些药物的患者。在索引事件（PAH诊断和药物起始）后的1年、3年和5年间隔评估结局。倾向评分匹配用于考虑人口统计学和合并症。匹配队列包括A组中的7998名患者和B组中的8006名患者。
在1年期间，A组7998名患者中有614名死亡（7.7%），而B组8006名患者中有1251名死亡（15.6%），风险差异为7.9%（p<0.0001）。在3年时，与使用SGLT2i抑制剂相关的死亡率优势仍然明显，A组7998名患者中有1012名死亡（12.7%），而B组8006名患者中有1930名死亡（24.1%），绝对风险差异为11.5%（p<0.0001）。到5年时，A组7998名患者中有1139名死亡（14.2%），B组8006名患者中有2190名死亡（27.4%），相应的风险差异为13.1%（p<0.0001）。
PAH患者使用SGLT2i与显著且持续降低死亡率相关。5年时绝对风险降低13%突出了对PAH管理产生变革性影响的潜力。有必要进行随机对照试验来证实这些发现并指导临床实践。
