Forty-four consecutive patients with IPAH (WHO classes II-III) were included in this study. After an initial assessment (clinical status, pulmonary hemodynamics, samples for adrenomedullin (ADM), ET-1 and brain natriuretic peptide (BNP) plasma levels), patients were treated with bosentan and followed-up for CW.
We observed CW in 24 patients. Actuarial rates of freedom from CW were 74 % at 1 year, 56 % at 2 years, and 43 % at 3 years. Patients with CW had a worse WHO functional class (II/III; no-CW 14/6 vs CW 5/19, p = 0.002), six-minute walk-test distance (no-CW 439 + 94 m vs CW 385 + 82 m, p = 0.04), mean pulmonary artery pressure (no-CW 47.4 + 10.6 mm Hg vs CW 56 + 12.6 mm Hg, p = 0.02) and pulmonary vascular resistance (PVR no-CW 12.5 + 4.8 WU vs CW 16.4 + 6.3 WU, p = 0.03) than the no-CW group. Moreover ET-1 (no-CW 14.1 + 4.2 pg/ml vs CW 21.3 + 6.3 pg/ml, p = 0.0001), ADM (no-CW 14.9 + 7 pg/ml vs CW 21.5 + 10.4 pg/ml p = 0.002) and BNP (no-CW 82.8 + 35.3 pg/ml vs CW 115.4 + 39.6 pg/ml, p = 0.007) plasma levels were significantly higher in the CW group than in the no-CW group. The multivariate Cox proportional hazards model identified WHO class III (RR 4.6, 95 % CI 14.6-1.45), ET-1 plasma levels (RR 1.1, 95 % CI 2.05-1.01) and PVR (RR 1.2, 95 % CI 1.3-1.03) as independent risk factors for CW.
These data confirm the high rate of CW in patients with IPAH treated with bosentan and document the impact of the endothelin system on CW of these patients.