PURPOSE: Examine the effect of adding sildenafil to bosentan on 6-minute walk distance (6MWD)in patients with pulmonary arterial hypertension (PAH) who were initiated on bosentan and did not achieve a satisfactory improvement in exercise tolerance over time.
METHODS: Eight patients with either idiopathic PAH or connective tissue disease (CTD) associated PAH were included in this study. Patients were followed prospectively with repeat 6MWD at least every 3 months. Baseline 6MWD (prior to initiation of bosentan), 3 month, 6 month, second baseline (prior to initiating combination therapy), 3 month and 6 month data were analyzed using ANOVA for repeated measures with specific comparisons.
RESULTS: We followed 6 females and 2 males. Seven patients had idiopathic PAH and 1 female had CTD-associated PAH. Mean age was 46.25 years (range 24-72). Individual as well as mean data for 6MWD are shown in figure 1. At 6 months following the initiation of bosentan, 6MWD increased by an average of 43 meters. Average time from initiation of treatment with bosentan to initiation of combination therapy was 310 days (range 180 to 600). Average 6MWD at the second baseline (prior to initiating combination therapy) was still higher than the first baseline by 23 meters. At six month following combination therapy 6MWD was 45 meters higher than the second baseline. Although these values are not significantly different, the overall increase in 6MWD 6 months following combination therapy was significantly higher than the first baseline by 68 meters.
CONCLUSION: These results show that, in patients who do not achieve a satisfactory improvement in exercise tolerance with monotherapy, initiating combination therapy (even after approximately 1 year of monotherapy treatment) may result in further improvement in exercise tolerance. Randomized controlled studies with a large number of patients are needed to address the benefit (improved quality of life and survival) of combination therapy in this group of patients.
CLINICAL IMPLICATIONS: Early initiation of combination therapy may prove beneficial in improving exercise tolerance and survival in patients with PAH.
DISCLOSURE: Hassan Al-Sharif, None.