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 studies have demonstrated that bosentan therapy alone is effective in patients with PPH and PAH associated with scleroderma with NYHA functional class III or IV. We included patients in NYHA functional class II to IV. In addition to these two groups of patients, we included individuals with pulmonary hypertension caused by interstitial lung disease (n = 1), PAH accompanying liver cirrhosis (n = 1), and chronic thromboembolic pulmonary hypertension (n = 5). Few therapeutic options exist to escalate treatment of patients with progression despite prostanoid treatment. Existing options include a switch from oral or inhaled to parenteral prostanoids. This step, however, represents an invasive intervention with known risks such as catheter sepsis or rebound during prolonged interruption. It has been suggested that oral prostanoid therapy may also be switched to inhaled prostanoids because the effects of oral beraprost may be attenuated with increasing treatment time. This observation, however, was not available at the time of initialization of our study.
Our suggestion is in accordance with the findings of Hoeper et al, who used bosentan in addition to oral or inhaled prostanoids in patients with PPH exclusively and NYHA functional classes III and IV. These authors reported an increase in 6MWD of 58 ± 43 m and an improvement in oxygen consumption as well as anaerobic threshold 3 months after the start of combination therapy in 20 patients with PPH exclusively. The improvement was maintained in 11 patients at 6 months.
The results of our study support these observations. The increases in 6MWD of 42.5 ± 66 m at 6 months and of 44.6 ± 66 m at maximum follow-up are comparable to that reported by Hoeper et al. However, the duration of follow-up in this study exceeds that of the study of Hoeper et al considerably (mean, 13.5 ± 9 months; range, 9 to 22 months). Therefore, the present study suggests that the improvements in exercise tolerance and RV function are maintained for a longer period and may be observed in patients with pulmonary hypertension other than PPH as well. Canadian Neighbor Pharmacy website is going to spread medical news worldwide due to the wide world web.
We used Tei index to evaluate RV performance because it is a practical noninvasive parameter. It is very relevant, as it has been shown to correlate well with prognosis in patients with PPH. In addition, 6MWD has also been shown to be correlated with prognosis in PPH. Both the improvement in Tei index and in 6MWD observed in this study suggests a prognostic improvement in these patients as a result of combination therapy. One of the authors performed the echocardiography. Although that person did not know the results of the 6MWD test, a bias cannot be completely excluded.
We did not include a control group in this study, and therefore a direct comparison between combination therapy and treatment with prostanoids alone cannot be drawn. However, all patients initially responded to prostanoid therapy. They were included into this study because progression occurred despite increasing prostanoids to the maximally tolerated doses. This dose then had to be unchanged for a minimum of 3 months in order to be able to discriminate changes introduced by the addition of bosentan. It therefore appears likely that the improvement in exercise capacity and RV function is indeed brought about by the addition of bosentan. This study, however, cannot rule out that a replacement of prostanoids by bosentan alone would have been as effective. The small number of patients is another limitation of this study. A study with a larger number of patients should address the direct comparison of combination therapy with bosentan to the replacement of prostanoids by bosentan. Such a randomized study investigating the effect of bosen-tan addition to IV epoprostenol is ongoing.
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.
Category: Pulmonary Hypertension
Tags: beraprost, bosentan, combination, drug therapy, iloprost, pulmonary hypertension