Bosentan for patients with chronic thromboembolic pulmonary hypertension.
BACKGROUND
Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease leading to worsening functional status and reduced survival for those patients who cannot undergo pulmonary endarterectomy (PEA). Pharmacotherapy with novel drugs for pulmonary hypertension may be useful in treating patients who are poor candidates for surgery, but there are still few clinical data on medical therapy for CTEPH. The aim of this prospective open-label, multicenter, study is to compare the efficacy of 1-year bosentan treatment to standard drugs in nonoperated patients with CTEPH.


METHODS
Thirty-four nonoperated patients with CTEPH were enrolled. Functional assessment included 6 minute walk test (6MWT), Borg index, WHO classification, arterial blood gases and echocardiography systolic pulmonary artery pressure (sPAP). Seventeen patients received bosentan (62.5 mg b.i.d. for 4 weeks and then 125 mg b.i.d.); 17 patients were treated with standard therapy alone.


RESULTS
At admission sPAP was 76.18+/-5.96 mmHg in bosentan group and 71.48+/-3.71 mmHg in controls, p(a)O(2) 64.68+/-2.25 mmHg in bosentan group, and 59.52+/-2.05 mmHg in controls, 6MWT 297.53+/-34.25 mt in bosentan group, and 268.47+/-36.54 mt in controls. After 12 months there were significant differences between the groups in the 6MWT (+57.24+/-22.21 m vs -73.13+/-21.23 m, p<0.001), dyspnoea index (Borg score 4.29+/-0.49 vs 7.06+/-0.32, p<0.001) and oxygenation (p(a)O(2) 65.93+/-3.76 mmHg vs 48.48+/-1.31 mmHg, p<0.001). The sPAP was stable after 12 months of bosentan (76.18+/-5.96 mmHg vs 71.00+/-5.41 mmHg, p=0.221) in contrast to controls (71.48+/-3.71 mmHg vs 80.44+/-4.70 mmHg, p=0.029).


CONCLUSIONS
The data of this open-label study in nonoperated CTEPH patients suggest an improvement in functional outcomes adding Bosentan to diuretics and oral anticoagulants. No improvement was observed using only standard drugs after 1-year.
Vassallo
Fabio Giuseppe
FG
Department of Pneumology, University Hospital of Trieste, Trieste, Italy.
Kodric
Metka
M
Scarduelli
Cleante
C
Harari
Sergio
S
Potena
Alfredo
A
Scarda
Angelo
A
Piattella
Marco
M
Cassandro
Roberto
R
Confalonieri
Marco
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D000077300:Bosentan; D002908:Chronic Disease; D004232:Diuretics / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D004417:Dyspnea / Q000188:drug therapy; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000188:drug therapy*; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome; D016138:Walking; D055815:Young Adult
D000925:Anticoagulants; D000959:Antihypertensive Agents; D004232:Diuretics; D013449:Sulfonamides; D000077300:Bosentan