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Adverse events of prostacyclin mimetics in pulmonary arterial hypertension: a systematic review and meta-analysis

Picken, C; Konstantinos, F; Eddama, M; Coghlan, G; Clapp, L; (2019) Adverse events of prostacyclin mimetics in pulmonary arterial hypertension: a systematic review and meta-analysis. Journal of Clinical Medicine (In press).

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Abstract

Prostacyclin mimetics (PMs) are effective for the treatment of pulmonary arterial hypertension (PAH). However, their clinical use may be limited by their adverse events. This study aims to quantify the different PM adverse events with regard to their selectivity towards the IP receptor and their administrative routes. The study included randomised placebo-controlled trials comparing iloprost, beraprost, treprostinil, and selexipag to placebo (published 2002-2016). We report the group efficacy differences between treatment and placebo by weighted and standardised mean difference. The probability of adverse events was determined by the odds ratio (OR). Of the 14 RCTs involving 3518 PAH patients, outcome and adverse event data were meta-analysed by drug type and route of administration. PM comparison demonstrated a more significant discontinuation of IP-selective agonist, selexipag, due to an adverse event (OR=2.2; 95% CI: 1.5, 3.3). Compared to placebo, site pain associated with subcutaneously administered treprostinil was the most significantly likely adverse event (OR=17.5; 95% CI: 11.1, 27.1). Parenteral PMs were associated with fewer adverse effects overall. The overall efficacy of PMs to improve 6-minute walk distance by 16.3 meters was significant (95% CI: 13.0, 19.7). Decreases in pulmonary vascular resistance index (SMD = -5.5; 95% CI: -10.1, -0.9; I2 = 98%) and mean pulmonary arterial pressure (SMD = -1.0; 95% CI: -2.6, -0.7; I2 = 99%) in treatment groups were found to be significant. Adverse event profiles varied in response to administration route and PM type but were not negated by use of a selective IP agonist. PM exposure to non-target IP receptors may underpin the number of AEs reported.

Type: Article
Title: Adverse events of prostacyclin mimetics in pulmonary arterial hypertension: a systematic review and meta-analysis
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Pulmonary arterial hypertension, prostacyclin, IP receptor, treprostinil, selexipag, iloprost, adverse events, beraprost
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: http://discovery.ucl.ac.uk/id/eprint/10071762
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