Usefulness of first-line combination therapy with epoprostenol and bosentan in pulmonary arterial hypertension: an observational study

J Heart Lung Transplant. 2012 Feb;31(2):150-8. doi: 10.1016/j.healun.2011.11.002. Epub 2011 Dec 3.

Abstract

Background: Recent guidelines have proposed first-line combination therapy as a potential strategy for the treatment of functional class IV pulmonary arterial hypertension (PAH).

Methods: We analyzed efficacy and safety of upfront epoprostenol and bosentan combination therapy in consecutive patients with idiopathic, heritable, or anorexigen-associated PAH and compared outcomes with matched controls treated by epoprostenol monotherapy.

Results: Data for 16 functional class III patients and 7 functional class IV patients were analyzed. Baseline 6-minute walk distance (6MWD) was 287 ± 133 meters, mean pulmonary artery pressure was 65 ± 12 mm Hg, cardiac index was 1.8 ± 0.3 L/min/m(2), and pulmonary vascular resistance (PVR) was 1493 ± 398 dynes/sec/cm(5). After 4 months, 6MWD and PVR significantly improved to 421 ± 100 meters and 784 ± 364 dynes/sec/cm(5), respectively. These improvements were maintained long-term (30 ± 19 months). At 1, 2, 3, and 4 years, overall survival estimates were 100%, 94%, 94%, and 74%, and transplant-free survival estimates were 96%, 85%, 77%, and 60%, respectively. Compared with matched controls started on epoprostenol monotherapy, there was a trend to an improvement in overall survival (p = 0.07).

Conclusions: Initial combination therapy with epoprostenol and bosentan in patients with severe PAH is associated with improvements in important outcomes such as functional class, exercise capacity, and hemodynamics. This combination strategy might also favorably affect overall and transplant-free survival.

MeSH terms

  • Adult
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Bosentan
  • Case-Control Studies
  • Drug Therapy, Combination
  • Epoprostenol / administration & dosage
  • Epoprostenol / adverse effects
  • Epoprostenol / therapeutic use*
  • Familial Primary Pulmonary Hypertension
  • Female
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / physiopathology
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Retrospective Studies
  • Severity of Illness Index
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Sulfonamides
  • Epoprostenol
  • Bosentan