Phosphodiesterase-5 Inhibitor Treatment is Associated with Improved Survival in Pulmonary Hypertension Associated with COPD in the PVRI GoDeep Meta-Registry

BACKGROUND: Patients with COPD frequently develop pulmonary hypertension (PH-COPD). Severe PH-COPD, identified by a pulmonary vascular resistance (PVR) >5 Wood Units (WU), is closely linked to impaired transplant-free survival. The impact of PH-targeting pharmacotherapy in this context remains unclear. RESEARCH QUESTION: Is PH-targeted therapy associated with improved transplant-free survival in PH-COPD? STUDY DESIGN AND METHODS: This study included PVRI GoDeep meta-registry patients with PH-COPD and available right heart catheterization at diagnosis. We investigated PH-targeted therapy prevalence and its association with transplant-free survival using diverse statistical methods, including Cox regression and subgroup analyses based on PH severity, comorbidities, and pulmonary function tests. Immortal time bias was addressed through a landmark approach. RESULTS: As of December 2023, the GoDeep meta-registry included 26981 patients (28% PH-Group 1, 13% PH-Group 2, 12% PH-Group 3, 10% PH-Group 4, 2% PH-Group 5, 26% undefined and 9% control). Out of these, 836 patients were diagnosed as PH-COPD and included in this analysis, with median age 66 [59,73]years, FEV1 51 [34,69]%predicted, mPAP 35 [28,44]mmHg, PVR 5 [4,8]WU, cardiac index 2.5 [2.0,2.9]L/min.m2, and mostly WHO functional class III were included. 5-year transplant-free survival was 42%, significantly worse than group 1 PH. A multivariable Cox proportional hazards model identified PVR, but not FEV1 as a major predictor of outcome. 418 patients (50%) received phosphodiesterase-5 inhibitor (PDE5i) therapy, which was associated with significantly reduced mortality: hazard ratio 0.65 [0.57,0.75] for the entire PH-COPD cohort and 0.83 [0.74,0.94] when performing landmark analysis. This PDE5i effect was robustly reproduced when performing subgroup analyses for patients with moderate/severe PH, various comorbidities, and supplemental oxygen requirement, and when assessing the impact of unobserved confounders. INTERPRETATION: PH-COPD patients exhibit poor transplant-free survival, with PVR being a predictor of mortality. In this meta-registry, PDE5i therapy was associated with a significant reduction in mortality across all tested models.

  • Tello, K.
  • Yogeswaran, A.
  • Majeed, R. W.
  • Kiely, D. G.
  • Lawrie, A.
  • Brittain, E.
  • Annis, J. S.
  • Olschewski, H.
  • Kovacs, G.
  • Hassoun, P. M.
  • Balasubramanian, A.
  • Konswa, Z.
  • Sweatt, A. J.
  • Zamanian, R. T.
  • Wilkins, M. R.
  • Howard, L.
  • Arvanitaki, A.
  • Giannakoulas, G.
  • Cajigas, H. R.
  • Frantz, R.
  • Williams, P. G.
  • Frauendorf, M.
  • Marquardt, K.
  • Antoine, T.
  • Fuenderich, M.
  • Richter, M.
  • Grimminger, F.
  • Ghofrani, H. A.
  • Wilhelm, J.
  • Seeger, W.

Keywords

  • Copd
  • meta-registry
  • phosphodiesterase-5 inhibitor therapy
  • pulmonary hypertension
Publication details
DOI: 10.1016/j.chest.2024.08.016
Journal: Chest
Work Type: Original
Access number: 39182575
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