Clinical TrialClinical effects of endothelin receptor antagonism with bosentan in patients with severe chronic heart failure: results of a pilot study
Section snippets
Methods
All patients had dyspnea or fatigue at rest or on minimal exertion (New York Heart Association class IIIB-IV) for at least 2 months and a left ventricular ejection fraction within 6 months that was <0.35 despite treatment with diuretics and a converting-enzyme inhibitor (unless intolerant). Patients were also required either to have been hospitalized for heart failure within 12 months or to be unable to walk more than 375 meters during a 6-minute corridor walk test. Treatment with digoxin,
Results
Enrollment into the study began on March 31, 1997, and 370 patients were randomized at 130 centers over 6 to 7 months. During this time, analysis of blinded data revealed a high incidence of liver function abnormalities, and this observation led to a decision by the Steering Committee and the sponsor to reduce the target dose of bosentan (to 125 mg twice daily) in subsequent trials with the drug. When informed of this decision, the Data and Safety Monitoring Board recommended orderly closure of
Discussion
Treatment with bosentan was not associated with any benefit when all randomized patients were included in the analysis, but when the duration of follow-up was considered (as specified in the original protocol), the results of the present study suggest that the clinical responses to endothelin antagonism with bosentan may be dependent on the duration of treatment. Short-term administration of the drug was associated with an increased risk of worsening heart failure, which appeared to be most
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Supported by a grant from Hoffmann-LaRoche Ltd., Basel, Switzerland.