Allopurinol in patients with pulmonary hypertension associated with chronic lung disease

Abstract

Background: Oxidative stress (OS) has been implicated in the development of pulmonary hypertension (PH) and ventricular hypertrophy. Xanthine oxidase is a well-recognised source of reactive oxygen species, which lead to OS. The aim of this proof of concept study was to assess whether allopurinol (xanthine oxidase inhibitor) would reduce right ventricular mass (RVM) in patients with PH-associated chronic lung disease (PH-CLD). Methods: We conducted a randomised, double-blind, parallel-group, placebo-controlled trial in patients with PH-CLD (93% COPD, 7% IPF) who were randomly assigned to receive allopurinol or placebo for 12 months. The primary outcome was the mean change in RVM, as assessed by cardiac magnetic resonance imaging (CMRI). Secondary outcomes included quality of life (QOL), spirometry and six-minute walk test (6MWT). Results: Seventy-one patients were recruited: mean age 71 years, mean pulmonary arterial pressure 30 mm Hg, FEV1 60% and resting SpO2 96%. After 12 months, there was no significant difference in the change in RVM from baseline (allopurinol 1.85g vs placebo 0.97g with mean difference 0.88g, CI −4.77 to 3.01, p =0.7). There were also no significant changes in other cardiac parameters measured on MRI, in QOL, spirometry and 6MWT. Subgroup analysis showed that allopurinol significantly reduced RVM compared to placebo with-6.16g vs 0.75g and mean difference 6.92g (CI 1.14 to 12.69, p = 0.02) in COPD patients with more severe airflow limitation. Conclusion: Allopurinol had no overall impact on patients with PH-CLD but had potential benefit in COPD patients with more severe airflow limitation.