Ambrisentan and Tadalafil combination therapy for pulmonary arterial hypertension

AF Balderrama, ME Ching, A Evangelista, MA Lontok

Background: Pulmonary arterial hypertension (PAH) remains a devastating chronic and progressive disease characterized by elevations in mean pulmonary arterial pressure and pulmonary vascular resistance. It is a complex, progressive disease with several mechanisms, including the endothelin, nitric oxide and prostacyclin pathways with a grave prognosis and a median survival of 2.8 years for untreated patients. This study aims to assess the efficacy of combination therapy of Ambrisentan and Tadalafil versus Ambrisentan alone in the reduction of primary clinical outcomes such as mortality, hospitalization and worsening clinical status among PAH patients.

Methods: A comprehensive search on Pubmed, Cochrane, Embase, SciSearch and was done by all members of the research team to retrieve all studies relevant to the research topic. All members of the research team individually appraised all retrieved studies and any discrepancies were discussed and deliberated by all members of the group. The primary outcome of interest is improvement of mortality and hospitalization.

Results: A total of 5 articles were screened and 2 studies were included for quantitative analysis. The mortality rate was not statistically significant (OR 1.55; 95% CI 0.35 to 6.88) between patients given Ambrisentan/Tadalafil and patients given Ambristentan alone. Hospitalization from worsening pulmonary artery hypertension favored Ambrisentan/Tadalafil (OR 0.24; 95% CI 0.11 to 0.53), while safety and tolerability between the two groups did not show statistically significant difference (OR 1.90; 95% CI 0.85 to 4.25).

Conclusion: Combination therapy showed significant reduction in the hospitalization due to worsening pulmonary artery hypertension compared to ambisentran monotherapy. However, combination therapy did not show significant benefit over monotherapy for all cause mortality. A limitation of this meta-analysis is the scarcity of available randomized controlled trials involving combination therapy of tadalafil and ambrisentan.