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

Abstract

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