Outcomes of pulmonary arterial hypertension therapy in Australia: is monotherapy adequate?

Intern Med J. 2017 Oct;47(10):1124-1128. doi: 10.1111/imj.13495.

Abstract

Background: In Australia, government-subsidised treatment of pulmonary arterial hypertension (PAH) is limited to monotherapy. Recent international guidelines advocate that initial combination therapy be considered for all symptomatic PAH patients.

Aim: To characterise 'real-life' outcomes in PAH patients initiated on monotherapy.

Methods: We performed a retrospective analysis of 100 consecutive PAH patients at a single centre who were commenced on monotherapy for PAH between 2004 and 2015. The composite clinical end-point of 'treatment failure' was prospectively defined as (i) >15% fall in 6-min walk distance (6MWD) on follow up, (ii) physician judgement of inadequate treatment response, (iii) adverse drug effect requiring cessation and (iv) death or transplantation.

Results: At initiation of therapy, mean age was 54 ± 18 years, and underlying diagnoses included idiopathic (36%), connective tissue disease-associated (37%) and congenital heart disease-associated-PAH (25%). Baseline 6MWD was 360 ± 140 m, and 75% were in either the New York Heart Association functional classes III or IV. Over a median follow up of 38 months (interquartile range 20-67), 62% of the subjects met the criteria for a clinical failure event. Median time to monotherapy failure was 24 months (95% confidence interval 14-34), with death or transplantation being the most common clinical failure event. Estimated 1-, 3- and 5-year survival rates from time of treatment initiation were 92, 75 and 66%.

Conclusion: The majority of patients failed initial monotherapy therapy within 2 years of treatment initiation. Broader access to approved PAH agents is needed to enable combination therapy in line with evidence-based international guidelines.

Keywords: Australia; pulmonary arterial hypertension; survival; treatment failure; treatment of pulmonary hypertension.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / administration & dosage*
  • Australia / epidemiology
  • Bosentan
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension, Pulmonary / diagnosis
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / epidemiology*
  • Male
  • Middle Aged
  • Phosphodiesterase 5 Inhibitors / administration & dosage
  • Prospective Studies
  • Retrospective Studies
  • Sildenafil Citrate / administration & dosage
  • Sulfonamides / administration & dosage
  • Treatment Failure
  • Young Adult

Substances

  • Antihypertensive Agents
  • Phosphodiesterase 5 Inhibitors
  • Sulfonamides
  • Sildenafil Citrate
  • Bosentan