Bosentan for patients with chronic thromboembolic pulmonary hypertension

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease leading to worsening functional status and reduced survival for those patients who cannot undergo pulmonary endarterectomy (PEA). Pharmacotherapy with novel drugs for pulmonary hypertension may be useful in treating patients who are poor candidates for surgery, but there are still few clinical data on medical therapy for CTEPH. The aim of this prospective open-label, multicenter, study is to compare the efficacy of 1-year bosentan treatment to standard drugs in nonoperated patients with CTEPH. Patients and methods: Thirty-four nonoperated patients with CTEPH were enrolled. Functional assessment included 6 minute walk test (6MWT), Borg index, WHO classification, arterial blood gases and echocardiography systolic pulmonary artery pressure (sPAP). Seventeen patients received bosentan (62.5 mg bid for 4 weeks and then 125 mg bid); 17 patients were treated with standard therapy alone. Results: At admission sPAP was 76.18 +/- 5.96 mmHg in bosentan group and 71.48 +/- 3.71 mmHg in controls, p_aO₂ 64.68 +/- 2.25 mmHg in bosentan group, and 59.52 +/- 2.05 mmHg in controls, 6MWT 297.53 +/- 34.25 mt in bosentan group, and 268.47 +/- 36.54 mt in controls. After 12 months there were significant differences between the groups in the 6MWT (+ 57.24 +/- 22.21 m vs - 73.13 +/- 21.23 m, p <0.001), dyspnoea index (Borg score 4.29 +/- 0.49 vs 7.06 +/- 0.32, p <0.001) and oxygenation (p_aO₂ 65.93 +/- 3.76 mmHg vs 48.48 +/- 1.31 mmHg, p <0.001). The sPAP was stable after 12 months of bosentan (76.18 +/- 5.96 mmHg vs 71.00 +/- 5.41 mmHg, p = 0.221) in contrast to controls (71.48 +/- 3.71 mmHg vs 80.44 +/- 4.70 mmHg, p = 0.029). Conclusion: The data of this open-label study in nonoperated CTEPH patients suggest an improvement in functional outcomes adding Bosentan to diuretics and oral anticoagulants. No improvement was observed using only standard drugs after 1-year.