Switch of patients with pulmonary arterial hypertension after withdrawal of the endothelin receptor antagonist sitaxentan

Due to hepatotoxicity, the ERA sitaxentan was withdrawn in December 2010. We describe the characteristics and treatment pathways of the 285 patients with pulmonary arterial hypertension (PAH) that were switched from sitaxentan to other drugs in COMPERA, an ongoing European registry that prospectively collects data from consecutive patients with pulmonary hypertension. In 6 (2%) patients therapy was discontinued completely, while 279 patients were switched to other drugs: 124 (44%) to bosentan, 141 (49%) to ambrisentan, 12 (4%) to PDE-5 inhibitors, and 2 to other PAH specific therapies. Patients switched to bosentan or ambrisentan had similar age (62 vs. 64 years), gender distribution (females 64% vs 70%), NYHA class (III: 62% vs 60%), disease duration (4.3 vs 4.5 years) and 6-minute walk distance (384 vs 374 meters). During follow-up, ERA therapy was stopped in 12 (10%) patients that had been switched to bosentan (6 lack of tolerability including 1 increased transaminases, 6 other) and in 15 (10.6%) patients that had been switched to ambrisentan (13 lack of tolerability including 2 cases of increased hepatic transaminases, 2 lack of efficacy). 5 patients (4.0%) originally switched to bosentan were later prescribed ambrisentan (3 elevated transaminases, 1 increasing dyspnoea, 1 intolerance to bosentan), and 12 (8.5%) originally switched to ambrisentan were later prescribed bosentan (2 oedema, 1 emesis, 1 gastric intolerance, 2 ulcers, 2 headache, 1 increasing dyspnoea, 3 other). Most patients were successfully switched from sitaxentan to another ERA. A minority had tolerability problems and needed further change or discontinuation of ERA therapy.