Combining bosentan and sildenafil in pulmonary arterial hypertension patients failing monotherapy: real-world insights

Eur Respir J. 2015 Aug;46(2):414-21. doi: 10.1183/09031936.00209914. Epub 2015 May 28.

Abstract

Pulmonary arterial hypertension is a severe disease with a complex pathogenesis, for which combination therapy is an attractive option.This study aimed to assess the impact of sequential combination therapy on both short-term responses and long-term outcomes in a real-world setting.Patients with idiopathic/heritable pulmonary arterial hypertension, or pulmonary arterial hypertension associated with congenital heart disease or connective tissue disease and who were not meeting treatment goals on either first-line bosentan or sildenafil monotherapy, were given additional sildenafil or bosentan and assessed after 3-4 months. Double combination therapy significantly improved clinical and haemodynamic parameters, independent of aetiology or the order of drug administration. Significant improvements in functional class were observed in patients with idiopathic/heritable pulmonary arterial hypertension. The 1-, 3- and 5-year overall survival estimates were 91%, 69% and 59%, respectively. Patients with pulmonary arterial hypertension associated with connective tissue disease had significantly poorer survival rates compared to other aetiologies (p<0.003).The favourable short-term haemodynamic results and good survival rates, observed in patients receiving both bosentan and sildenafil, supports the use of sequential combination therapy in patients failing on monotherapy in a real-world setting.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / therapeutic use
  • Bosentan
  • Cause of Death
  • Child
  • Connective Tissue Diseases / complications
  • Drug Therapy, Combination
  • Exercise Test
  • Familial Primary Pulmonary Hypertension / complications*
  • Female
  • Heart Defects, Congenital / complications
  • Hemodynamics / drug effects
  • Humans
  • Hypertension, Pulmonary / complications
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / mortality
  • Italy
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Retrospective Studies
  • Sildenafil Citrate / administration & dosage*
  • Sildenafil Citrate / therapeutic use
  • Sulfonamides / administration & dosage*
  • Sulfonamides / therapeutic use
  • Survival Rate
  • Treatment Outcome
  • Vasodilator Agents / administration & dosage*
  • Vasodilator Agents / therapeutic use
  • Young Adult

Substances

  • Antihypertensive Agents
  • Sulfonamides
  • Vasodilator Agents
  • Sildenafil Citrate
  • Bosentan