Chest
Volume 128, Issue 2, August 2005, Pages 709-713
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Clinical Investigations
Bosentan Improves Exercise Tolerance and Tei Index in Patients With Pulmonary Hypertension and Prostanoid Therapy

https://doi.org/10.1378/chest.128.2.709Get rights and content

Study objective

Pulmonary arterial hypertension (PAH) is a progressive disease with a bad prognosis. Prostanoids are well established in the medical treatment of this disease. Treatment of patients with progressive disease despite prostanoids remains a therapeutic challenge. In this study, we examined the effect of adding bosentan, an endothelin antagonist, to existing prostanoid therapy on exercise capacity (6-min walking distance [6MWD]) and right ventricular (RV) function (Tei index) in patients with progressive pulmonary hypertension

Design

Prospective, nonrandomized, open-label study

Setting

University hospital

Patients

Sixteen patients with pulmonary hypertension (PAH, n = 10; pulmonary hypertension due to other cause, n = 6) with progressive disease receiving either beraprost (n = 3), inhaled iloprost (n = 10), or iloprost IV (n = 3)

Interventions

Combination therapy with bosentan (final dosage, 125 mg bid) was initiated following an interval of 3-months minimum of unchanged prostanoid therapy

Measurements and results

Tei index, 6MWD, and New York Heart Association (NYHA) functional class were assessed prior to the initiation of combination therapy (baseline), at 6 months after initiation of combination therapy, and every 3 months thereafter. Two patients were followed up for 6 months only; all remaining patients reached a mean follow-up period (± SD) of 13.5 ± 5.0 months (range, 9 to 22 months). 6MWD increased by 42.5 ± 66 m at 6 months and 44.6 ± 66 m at the last follow-up (both time points vs baseline, p < 0.001), and Tei index improved by − 0.13 ± 0.08 at 6 months and − 0.13 ± 0.11 at the last follow-up (both time points vs baseline, p < 0.001). All patients reported subjective improvements. Nine of 16 patients exhibited improvement in NYHA functional class at 6 months. No side effects occurred that required dose adjustment or discontinuation of the study medication

Conclusion

Bosentan administered to patients with progressive pulmonary hypertension receiving prostanoids resulted in an increased exercise capacity and an improved RV function. Bosentan therefore appears to be well suited for combination therapy with prostanoids in selected patients pending results of ongoing randomized trials

Section snippets

Patients

Sixteen consecutive patients treated with prostanoids for a minimum of 12 months (Table 1) were included in this prospective, nonrandomized, open-label study. Patients were included when progressive pulmonary hypertension was noted despite prostanoid treatment. Progression of disease was defined as follows: (1) a decline of > 15% in 6MWD compared with the individual best value, (2) a decline in cardiac index to < 2 L/min/m2, and/or (3) a failure to increase in cardiac index to > 2 L/min/m2

6MWD

Figure 1 depicts the results of the 6MWD test. A significant increase in the walking distance was apparent at 6 months after initiation of combination therapy. This improvement was still maintained at the maximum time of follow-up. The increase in the 6MWD was 42.5 ± 66 m at 6 months and 44.6 ± 66 m at the maximum time of follow-up. Six months after initiation of combination therapy the 6MWD was improved in 11 patients (minimum, 16 m; maximum, 196 m), unchanged in 1 patient, and reduced in 4

Discussion

Our findings demonstrate that the addition of the dual endothelin receptor antagonist bosentan to prostanoid therapy significantly improves 6MWD as an indication of increased exercise tolerance and Tei index as an echocardiographic parameter summarizing RV function, in patients with progressive PAH and pulmonary hypertension due to chronic thromboembolic hypertension and due to interstitial lung disease. Several studies14, 15, 16 have demonstrated that bosentan therapy alone is effective in

Conclusion

The present study reports our experience of additional bosentan therapy in patients with progressive pulmonary hypertension despite maximally tolerated prostanoid therapy. The addition of bosentan resulted in a significant improvement of exercise capacity and RV function. This improvement was observed in patients with both PAH and those with pulmonary hypertension of other causes and was maintained for a mean follow-up period of 13.5 months.

References (21)

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