title: Beyond a single pathway: combination therapy in pulmonary arterial hypertension.
abstract: There is a strong rationale for combining therapies to simultaneously target three of the key pathways implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Evidence to support this strategy is growing, and a number of studies have demonstrated that combination therapy, administered as either a sequential or an initial regimen, can improve long-term outcomes in PAH. Dual combination therapy with a phosphodiesterase-5 inhibitor and an endothelin receptor antagonist is the most widely utilised combination regimen. However, some patients fail to achieve their treatment goals on dual therapy and may benefit from the addition of a third drug. The use of triple therapy in clinical practice was previously reserved for patients with severe disease due to the need for parenteral administration of prostanoids. Although triple therapy with parenteral prostanoids plays a key role in the management of severe PAH, the approval of oral therapies that target the prostacyclin pathway means that all three pathways can now be targeted with oral drugs at an earlier disease stage. Furthermore, there is evidence demonstrating that this approach can delay disease progression. Based on the evidence available, it is becoming increasingly clear that all PAH patients should be offered the benefits of combination therapy.
authors.affiliation: Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France olivier.sitbon@bct.aphp.fr.|AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.|INSERM UMR_S 999, Le Plessis Robinson, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Sitbon
authors.affiliation: National Pulmonary Hypertension Unit, Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: Sean
authors.initials: S
authors.lastname: Gaine
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use*; D062186:Arterial Pressure / Q000187:drug effects*; D004359:Drug Therapy, Combination; D019317:Evidence-Based Medicine; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D058990:Molecular Targeted Therapy; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents