A systematic review of transition studies of pulmonary arterial hypertension specific medications

Abstract

Pulmonary arterial hypertension (PAH) is a progressive potentially fatal disease. Multiple pharmacologic options are now available, which facilitated transitions between different therapeutic options, although the evidence for such transitions has not been well described. We sought to review the evidence supporting the safety and/or efficacy of transitioning between PAH-specific medications. We performed a systematic review of all published studies in the Medline database between 1 January 2000 and 30 June 2016 reporting on any transition between the currently Food and Drug Administration (FDA)-approved PAH-specific medications. Studies reporting on three or more adult patients published in the English language reporting on transitions between FDA-approved PAH medications were extracted and tabulated. Forty-one studies met the selection criteria, nine of which included less than eight patients (and thus were reported separately in the supplement), for a total of 32 studies. Transitioning from parenteral epoprostenol to parenteral treprostinil appears to be safe and efficacious in patients who have less severe disease and more favorable hemodynamics. Transitioning from a prostacyclin analogue to an oral medication may be successful in patients who have favorable hemodynamics and stable disease. There is conflicting evidence supporting the transition from a parenteral to an inhaled prostacyclin analogue, even in patients who are on background oral therapy. Currently, the only evidence in support of transitioning between oral PDE5 inhibitors is from sildenafil to tadalafil. Patients on higher doses of sildenafil are more likely to fail. In patients with liver abnormalities due to bosentan or sitaxentan, the transition to ambrisentan appears to be safe and can result in clinical improvement. Studies regarding PAH medication transitions are limited. Patients who have less severe disease, better functional status, and are on lower medications doses may be more successful at transitioning.

Risk stratification and medical therapy of pulmonary arterial hypertension

“…epoprostenol to i.v. treprostinil was achievable around 80% of the time [84]. Transition from parenteral epoprostenol to the thermostable form was generally achievable [84].…”

“…There have been conflicting outcomes in the transition from parenteral prostacyclins to inhaled or oral prostacyclins [84]. When discontinuation of bosentan is necessary due to liver function test elevations, transitioning to ambrisentan [85] or macitentan is safe.…”

Combination Therapy in Pulmonary Arterial Hypertension: Gleaning a Practical Approach from the Randomized Trials

“…Significant experience has been gained in transitioning PAH patients from parenteral to oral agents, from one or more oral agents to others. 18 In particular, transitioning patients from parenteral prostanoid to oral treprostinil or selexipag must be an individualized process based on multiple patient factors.…”

Measuring pulmonary arterial compliance: mission impossible? Insights from a novel in vivo continuous‐flow based experimental model

“…Whether the observed decrease in resistance is due to a passive mechanical effect or mediated by a decreased vasomotor tone is a relevant question that cannot be answered in our study since vasomotor tone was not blocked. Although it is a very important topic in the pulmonary circulation witnessed by positive clinical results on pulmonary vasodilators 17 and by the physiological relevance of hypoxic vasoconstriction, 18 the exact role and pathways of pulmonary vasomotor tone in normal lungs at rest and at exercise is still under investigation with some argument in favor of passive control 19 and some for active control. 20 Transition from pulsatile shear stress to constant shear stress should have an impact on vasoactive mediators; however, the phenomenon is complex and deserves attention that extends the primary goal of our experiment.…”