JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
REVIEW
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The role of combination therapy in managing pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a complex, progressive disease with several pathobiological mechanisms, including the endothelin, nitric oxide and prostacyclin pathways. Current treatments for PAH target one of these pathways and, in more severe cases or instances of disease worsening, may be combined with a view to target multiple pathways in parallel. Treatment combination is performed sequentially (as an intensification from initial monotherapy) or upfront (use of two or more therapies in treatment-naïve patients). Whilst combination therapy has been historically considered to be an option for the treatment of PAH, supporting evidence was typically limited to expert opinion, clinical experience and registry data. Data from randomised controlled trials on sequential combination therapy in particular has grown in recent years, resulting in a change in the level of recommendations in the latest update to the PAH treatment algorithm. However, short-term trials have shown inconsistent results, and have not been powered to assess morbidity/mortality outcomes. More recent data from long-term trials suggest a potential clinical benefit associated with sequential combination therapy. In this review we will introduce the concept of combination therapy, consider the latest evidence for both sequential and upfront combination therapy, and discuss additional considerations when initiating combination therapy in clinical practice.

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