First-line Bosentan and Sildenafil Combination Therapy for Pulmonary Arterial Hypertension

Launched by UNIVERSITY OF CALGARY · Nov 23, 2010

Keywords

ClinConnect Summary

Current treatment paradigms for PAH suggest adopting goals of therapy with relatively objective parameters such as 6 minute walk distance to determine when to add a second oral agent (1). This often entails observing deterioration in the patient on a single agent before instituting the second one. This strategy could be problematic, as patients may never recover the function lost due to progressive PAH (2). In addition, given the malignant nature of the clinical course of PAH in many cases and the nature of the underlying proliferative vasculopathy, some have argued that altering this parad...

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Eligibility criteria

• Inclusion Criteria:
• • Patients with symptomatic Functional Class III PAH in the following categories: Idiopathic (IPAH), Familial (FPAH), Associated with connective tissue disease, Associated with drugs or toxins
• • PAH diagnosed by right heart catheterization, defined as: mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg, PVR \> 3 mmHg/l/min (Wood units) or \> 240 dyn sec cm-5, pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg
• • Baseline 6 MWT distance \> 150 and \< 450 m
• Exclusion Criteria:
• • Treatment with ERAs other than bosentan;
• • Treatment with PDE5 inhibitors other than sildenafil;
• • Treatment with any prostanoid;
• • PAH associated with thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders and splenectomy; valvular disease with valvular lesions to be excluded by echocardiogram within 2 years prior to randomization
• • Restrictive lung disease: total lung capacity (TLC) \< 60% of normal predicted value;
• • Obstructive lung disease: forced expiratory volume/forced vital capacity (FEV1/FVC) \< 50%