Bosentan up-front or sequential add-on combination treatment for pulmonary arterial hypertension: Long-term effects and prognosis / 第二军医大学学报

ABSTRACT

Objective To investigate the long-term effects and safety of bosentan combination treatment (up-front combination and sequential add-on combination) for pulmonary arterial hypertension (PAH) patients and the prognosis of the patients. Methods In this open and observational study, a total of 104 patients who were diagnosed as having PAH in the Department of Pulmonary Circulation and Cardiology, Shanghai Pulmonary Hospital, were given bosentan (twice a day) before treatment from Jul. 2007 to Jan. 2013. According to the treatment regimen, the patients were divided into up-front combination group or sequential add-on combination group, and the patients were followed up till Jun. 2013. Then the improvements and the survival rates of the patients were evaluated and compared before and after treatment. Results The median treatment time with bosentan was (22.6±15.8) months. The WHO functional class had no obvious worsening in 68.1% of patients with bosentan treatment, with the situation improved in 6 patients and steady in 56. The lgNT-proBNP value was decreased from 2.8±0.8 to 2.5±0.2, but showing no significant difference (P=0.15). Echocardiogram examination found that the pulmonary arterial systolic pressure (PASP) decreased from (95.2±21.3)mmHg (1 mmHg = 0.133 kPa) to (88.6±24.4)mmHg (P=0.009); ejection fraction (EF) increased from (73.6±9.3)% to (77.4±9.0)%(P=0.02); transverse size of right artial (RA-T size) and transverse size of right ventricular (RV-T size) showed no changes. Hemodynamic observations found that the mean PAP(mPAP) and mean right arterial pressure (mRAP) showed no change; pulmonary vascular resistance (PVR) decreased from (16.4±8.4)Wood U/m2to (13.9±8.0)Wood U/m2, but showing no significant difference (P=0.06); and cardiac output (CO) increased from (3.8±2.0) L/min to (4.8±2.3) L/min (P=0.04). The results of Kaplan-Meier survival estimates for 1, 2, 3, 4 and 5 years were 92.5%, 83.7%, 71.7%, 67.2% and 57.6%, respectively. The 1, 2, 3 and 4 years survival rates of patients were 95.1%, 88.9%, 84.2% and 77.7% in the up-front combination group, and 92.3%, 79.4%, 53.3% and 26.6% in the sequential add-on combination group, respectively, with significant difference found between the two groups(P=0.038). Only one patient in our study stopped bosentan due to severe facial edema. Conclusion Long-term bosentan combination treatment can prevent cardiac function worsening in PAH patients, increasing cardiac output and with satisfactory safety. Moreover, up-front combination therapy with bosentan has a better prognosis than sequential add-on combination therapy for PAH patients.