• Pulmonary Clinical Trials
• Rheumatological Autoimmune Disorders
• Thromboembolic Disease Hypertensive Disease

• Pulmonary Clinical Trials
• Rheumatological Autoimmune Disorders
• Thromboembolic Disease
• Pulmonary & Critical Care
• Hypertensive Disease

Patients with systemic sclerosis pulmonary arterial hypertension (SSc-PAH) have a worse prognosis than those with idiopathic PAH. Although the specific mechanisms are not known, it is thought to be related to persistent right ventricular (RV) dysfunction and pulmonary vascular remodeling despite guideline-directed management with a single agent for PAH. Dr. Mohamed A. Gashouta, MD, St. Luke's Hospital, Chesterfield, Missouri, USA, presented a 36-week, open-label, multicenter observational study evaluating upfront therapy with 2 drugs, tadalafil and ambrisentan, that target distinct pathways in treatment-naïve patients with SSc-PAH [NCT01178073; Gashouta MA et al. Am J Respir Crit Care Med].

The presenter reported findings for 17 of the 25 patients with SSc-PAH who had been treated with tadalafil 40 mg daily, a phosphodiesterase inhibitor, and ambrisentan 10 mg daily, an endothelin antagonist. The patients (mean age, 58.8 years) were predominantly female (88%), with limited (94%) as opposed to diffuse (6%) SSc-PAH disease. The mean baseline pulmonary arterial pressure (PAP) was 40 ± 16 mm Hg and pulmonary capillary wedge pressure (PCWP) was 9 ± 3.5 mm Hg.

The first primary end point, RV mass, as measured by computed magnetic resonance imaging, was significantly reduced over 36 weeks from 21.7 ± 10.6 g/m² to 18.0 ± 6.7 g/m² (p=0.04) with the combination therapy. The second primary end point, pulmonary vascular resistance (PVR), was also significantly reduced from baseline (8.1 ± 58 woods units) to 36 weeks (3.9 ± 3.5 woods units; p=0.0001).

Previous work by this group showed that pulmonary compliance (Pca; stroke volume over pulmonary pulse pressure) was an indicator of poor prognosis and survival in SSc-PAH [Campo A et al. Am J Respir Crit Care Med 2010]. The authors found that Pca, a secondary end point, was significantly improved from baseline (1.9 ± 1.2) to 36 weeks (2.9 ± 1.3; p=0.0007) with the combination therapy. There were also improvements in the secondary end points of ventricular mass index (VMI; 0.31 ± 0.11 at baseline to 0.27 ± 0.08 at 36 weeks; p=0.03) and 6-minute walking distance (6MWD; 361.3 ± 122.3 minutes at baseline to 405.5 ± 90 at 36 weeks; p=0.003). The combination treatment also significantly improved RV stroke volume (76.7 ± 16.5 mL to 94.6 ± 17.7 mL; p=0.007) and RV end systolic volume (RV ESV; 89.8 ± 28.3 mL to 73.1 ± 28.8 mL; p=0.02) over the 36 weeks.

These results suggest that treatment with tadafil and ambrisentan in treatment-naïve patients with SSc-PAH leads to improvement in a number of clinical (6MWD), functional (RV mass index, VMI, RV ESV), and hemodynamic (PVR, Pca, stroke volume) parameters. Additional larger, randomized studies are necessary to determine if combination therapy is superior to guideline-based therapy and whether it results in a survival benefit.

• © 2014 MD Conference Express®