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Lajoie AC, Bonnet S, Provencher S. Combination therapy in pulmonary arterial hypertension: recent accomplishments and future challenges. Pulm Circ. 2017;7(2):312-325doi: 10.1177/2045893217710639.
Lajoie, A. C., Bonnet, S., & Provencher, S. (2017). Combination therapy in pulmonary arterial hypertension: recent accomplishments and future challenges. Pulmonary circulation, 7(2), 312-325. https://doi.org/10.1177/2045893217710639
Lajoie, Annie-Christine, et al. "Combination therapy in pulmonary arterial hypertension: recent accomplishments and future challenges." Pulmonary circulation vol. 7,2 (2017): 312-325. doi: https://doi.org/10.1177/2045893217710639
Lajoie AC, Bonnet S, Provencher S. Combination therapy in pulmonary arterial hypertension: recent accomplishments and future challenges. Pulm Circ. 2017 Apr-Jun;7(2):312-325. doi: 10.1177/2045893217710639. Epub 2017 May 30. PMID: 28597774; PMCID: PMC5467950.
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Pulm Circ. 2017 Apr-Jun;7(2):312-325. doi: 10.1177/2045893217710639. Epub 2017 May 30.

Combination therapy in pulmonary arterial hypertension: recent accomplishments and future challenges.

Pulmonary circulation

Annie-Christine Lajoie, Sebastien Bonnet, Steeve Provencher

Affiliations

  1. 1 Pulmonary Hypertension Research Group, Canada.
  2. 2 Institut universitaire de cardiologie et de pneumologie de Québec Research Center, Laval University, Quebec City, Canada.
  3. 3 Department of Medicine, Université Laval, Québec, Canada.

PMID: 28597774 PMCID: PMC5467950 DOI: 10.1177/2045893217710639

Abstract

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by a progressive increase in pulmonary vascular resistance, ultimately leading to right heart failure and death. Throughout the past 20 years, numerous specific pharmacologic agents, including phosphodiesterase-5 inhibitors, endothelin receptor antagonists, prostaglandins, and more recently, soluble guanylate cyclase stimulators and selective IP prostacyclin receptor agonist, have emerged for the treatment of PAH. Early clinical trials were typically of short-term duration, comparing the effects of PAH-targeted therapies versus placebo and using exercise tolerance as the primary endpoint in most trials. A meta-analysis of these trials documented a reduction in short-term mortality of ∼40% with monotherapy. More recently, we have witnessed a progressive shift in PAH study designs using longer event-driven trials comparing the effects of upfront and sequential combination therapy on clinical worsening that is perceived as a more clinically relevant outcome measure. Recent meta-analyses also documented that combination therapy significantly reduced the risk of clinical worsening by ∼35% compared with monotherapy alone. In this review article, we will discuss the evolution of treatments and clinical trial design in the field of PAH over the past decades with a special focus on combination therapy and its current role in the management of PAH. We will also detail unresolved questions regarding the future of PAH patients' care and the challenges of future clinical trials.

Keywords: clinical trials; endothelin; phosphodiesterase type 5; prostaglandins; pulmonary arterial hypertension combination therapy; pulmonary hypertension

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