Initial combination of macitentan and tadalafil in newly diagnosed patients with pulmonary arterial hypertension (PAH): results from the OPTIMA study

OPTIMA (EudraCT 2015-002078-19) is an ongoing prospective, multicenter, single-arm, open-label trial evaluating the efficacy (at Week 16), safety and tolerability of initial combination therapy with macitentan (10 mg once daily) and tadalafil (40 mg once daily) in newly diagnosed adult PAH patients [WHO functional class (WHO FC) II-III]. Treatment is initiated with macitentan 10 mg and tadalafil 20 mg on the same day; after 1 week the tadalafil dose is increased to 40 mg. To date, 16 patients have completed 16 weeks of treatment. In these patients the mean pulmonary vascular resistance (primary endpoint) was reduced by 54% (95% CI 48, 60) at Week 16. The mean change (95% CI) from baseline to Week 16 was 1.04 L/min/m^₂ (0.77, 1.31) for the cardiac index and -9.69 mmHg (-13.44, -5.94) for the mean pulmonary arterial pressure. Mean plasma NT-proBNP level (n=12) was reduced by 78% (95% CI 52, 90). Mean 6-minute walk distance increased by 27 m (95% CI -12, 66). The number of patients in WHO FC I/II, III and IV was 4, 12 and 0 at baseline, respectively, and 12, 4 and 0 at Week 16. The most frequent adverse events were peripheral edema, headache and anemia (3 patients each). There were no premature discontinuations, no hypotension and no increase in aminotransferases >3 times the upper limit of normal; 1 patient had a decrease in hemoglobin below 10 g/dL. In this study, newly diagnosed PAH patients received macitentan (10 mg) in combination with the recommended dose of tadalafil (40 mg) one week after treatment start. This regimen was well tolerated and led to improved hemodynamics indicative of improved right ventricular function.