ATS 2025: Pulmonary Vasodilator Therapy is Associated with Improved Survival in COPD-PH with Pulmonary Vascular Predominance

Introduction:

Pulmonary hypertension (PH) is a common comorbidity associated with COPD and is linked to increased mortality, frequent exacerbations and progressive disease trajectory. Given the heterogeneous nature of PH in COPD, studies examining use of pulmonary vasodilator therapy in COPD-associated pulmonary hypertension (COPD-PH) have demonstrated mixed results. This study aimed to evaluate whether pulmonary vasodilator therapy is associated with improved transplant-free survival in patients with COPD and more severe PH.

Methods:

A retrospective analysis was conducted in COPD patients with PH defined as mean pulmonary artery pressure (mPAP) > 20 mmHg. Patients were stratified into three groups: PVR > 5 Wood Units (WU), mPAP > 40 mmHg,   PVR > 5 WU and mPAP > 40 mmHg. Data on right heart catheterization, pulmonary function testing, pulmonary vasodilator therapy, and outcomes including death and lung transplant were collected. Transplant-free survival analysis was performed using Kaplan-Meier and multivariable Cox regression.

Results:

328 COPD-PH patients met the criteria of mPAP > 20 mmHg, out of which  85 had PVR > 5 WU, and 56 had mPAP > 40 mmHg and PVR > 5 WU. Among the entire COPD-PH group, the average FEV₁ was 49% predicted. 56 patients had died and 214 had received lung transplant. Among the severe COPD-PH group, average FEV1 was 50% predicted, PVR was 11.2 WU, and mPAP was 39.9 mmHg. Kaplan-Meier analysis showed significantly higher transplant-free survival in patients treated with pulmonary vasodilator therapy in the PVR > 5 WU group and PVR > 5 WU and mPAP > 40 mmHg group. Even when accounting for GOLD severity, COPD treatment and markers of clinical PH severity, PH therapy was significantly and independently associated with a reduced risk of death or transplant in the PVR > 5 WU group (HR 0.29, 95% CI 0.10–0.81, p = 0.02) and in the PVR >5 WU and mPAP> 40 mmHg group (HR 0.11, 95% CI 0.17–0.74, p = 0.02).

Conclusion:

In patients with COPD-PH, pulmonary vasodilator therapy was independently and significantly linked to a lower risk of death or transplant, particularly in those with more severe PH. This association remained significant even after adjusting for disease severity indicators such as GOLD stage, DLCO, 6MWD, oxygen requirement, BNP, and use of triple inhaler therapy. The strongest association of pulmonary vasodilator therapy and reduced risk of death or transplant was observed in patients with both PVR > 5 WU and mPAP > 40 mmHg, suggesting that individuals with a more pronounced pulmonary vascular phenotype may derive the greatest benefit from vasodilator therapy.

Am J Respir Crit Care Med 2025; 211: A7601

American Thoracic Society 2025 International Conference, May 18-21, San Francisco