Bosentan treatment in patients with primary pulmonary hypertension receiving nonparenteral prostanoids.
Primary pulmonary hypertension (PPH) is a life-threatening disease. Nonparenteral prostanoids, i.e. aerosolised iloprost or oral beraprost sodium show beneficial therapeutic effects but are not sufficiently active in all patients with this devastating disease. The purpose of the present study was to determine whether the endothelin-receptor antagonist bosentan is safe and effective in patients with PPH already receiving nonparenteral prostanoids. The effect of bosentan as add-on medication was studied in 20 patients with PPH, who received either inhaled iloprost (n=9) or oral beraprost (n=11) for a median period of 16+/-13 months, by means of the 6-min walk test and cardiopulmonary exercise testing. After 3 months of administration of bosentan in addition to prostanoids, the walking distance in the 6-min walk test increased by 58+/-43 m. Cardiopulmonary exercise testing revealed an increase in maximal oxygen consumption from 11.0+/-2.3 to 13.8+/-3.6 mL x kg(-1) x min(-1) accompanied by significant improvements in anaerobic threshold, oxygen pulse and minute ventilation/carbon dioxide production slope. Peak systolic blood pressure increased from 120+/-17 to 139+/-21 mmHg. Combination treatment was well tolerated by all patients. It is concluded that the addition of the endothelin-receptor antagonist bosentan to inhaled iloprost or oral beraprost therapy appears to be safe for patients with primary pulmonary hypertension, resulting in a marked increase in exercise capacity. Therefore, rigorous studies should address whether combination treatment is more effective than either therapeutic intervention alone.
Hoeper
M M
MM
Dept of Respiratory Medicine, Hannover Medical School, Hannover, Germany. hoeper.marius@mh-hannover.de
Taha
N
N
Bekjarova
A
A
Gatzke
R
R
Spiekerkoetter
E
E
D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077300:Bosentan; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005080:Exercise Test; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D016285:Iloprost / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D013449:Sulfonamides; D014665:Vasodilator Agents; C048081:beraprost; D011464:Epoprostenol; D016285:Iloprost; D000077300:Bosentan