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Adverse Events of Prostacyclin Mimetics in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis. | LitMetric

AI Article Synopsis

  • Prostacyclin mimetics (PMs) are effective in treating pulmonary arterial hypertension (PAH), but their use can be limited by side effects, leading to this study which evaluates the adverse events (AEs) linked to different PMs based on receptor selectivity and administration routes.
  • The study analyzed 14 clinical trials involving 3518 PAH patients, finding that selexipag (an IP-selective agonist) had a higher discontinuation rate due to adverse events, and that subcutaneous treprostinil was particularly associated with significant pain at the site of injection.
  • Overall, PMs improved patients' 6-minute walk distance and reduced pulmonary pressures, but adverse event profiles varied based on the type of PM and

Article 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 (AEs) with regard to their selectivity towards the prostacyclin (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 randomised clinical trials involving 3518 PAH patients, outcome and adverse event data were meta-analysed by drug type and route of administration. Prostacyclin mimetics comparison demonstrated a more significant discontinuation of the 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 significant 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; ² = 98%) and mean pulmonary arterial pressure (SMD = -1.0; 95% CI: -2.6, -0.7; ² = 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. Prostacyclin mimetics exposure to non-target IP receptors may underpin some AEs reported.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517977PMC
http://dx.doi.org/10.3390/jcm8040481DOI Listing

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