Key result
A single 25 mg oral dose of sildenafil added to established bosentan therapy significantly decreased mean pulmonary vascular resistance by 15% (95% CI -21 to -10; P<.0001).
Why the study?
Does a single oral dose of sildenafil reduce pulmonary vascular resistance in patients with stable pulmonary arterial hypertension on established bosentan therapy?
Does a single oral dose of sildenafil reduce pulmonary vascular resistance in patients with stable pulmonary arterial hypertension on established bosentan therapy?
Effect estimate: -15% change (95% CI -21 to -10)
p-value: p=<.0001
A single oral dose of sildenafil provides additional acute hemodynamic benefits when added to established bosentan therapy in patients with pulmonary arterial hypertension.
Acute hemodynamic benefit does not yet warrant routine sildenafil add-on in bosentan-treated PAH; leaves open long-term efficacy of combination therapy.
This study investigated the acute pharmacodynamic effects of sildenafil in patients with pulmonary arterial hypertension (PAH) and concomitant bosentan treatment, in view of a mutual pharmacokinetic interaction between the 2 drugs. This prospective, open-label, noncomparative, multicenter, phase II study enrolled 45 patients (>or=18 years) with stable PAH (idiopathic, familial, or related to corrected congenital systemic-to-pulmonary shunts, drugs, or toxins) and on bosentan treatment for at least 3 months. Patients underwent right heart catheterization to evaluate the acute hemodynamic effects of (a) inhaled nitric oxide (iNO) and (b) a single oral dose of sildenafil (25 mg). Mean pulmonary vascular resistance (PVR) decreased from baseline following iNO (-15%; 95% confidence limits: -21%, -8%; P = .0001). A statistically significant decrease from baseline in mean PVR was also observed 60 minutes following sildenafil administration (-15%; 95% confidence limits: -21%, -10%; P < .0001). The reduction in PVR following sildenafil was comparable to that resulting from iNO. There were no unexpected safety findings. The pharmacodynamic effect suggests that addition of sildenafil to bosentan treatment can elicit additional hemodynamic benefits. These data represent a rationale for long-term combination studies with the 2 compounds.
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Gruenig et al. (2009) studied Pulmonary arterial hypertension (n=45). Sildenafil vs. Baseline was evaluated on Change in mean pulmonary vascular resistance (PVR) from baseline (-15% change, 95% CI -21 to -10, p=<.0001). A single 25 mg oral dose of sildenafil added to established bosentan therapy significantly decreased mean pulmonary vascular resistance by 15% (95% CI -21 to -10; P<.0001).
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