Next Article in Journal
Prognostic Laboratory Parameters in Placental Abruption: A Retrospective Case-Control Study
Previous Article in Journal
A New Surgical Site Infection Risk Score: Infection Risk Index in Cardiac Surgery
Article Menu

Export Article

Open AccessArticle
J. Clin. Med. 2019, 8(4), 481; https://doi.org/10.3390/jcm8040481

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

1
Institute of Cardiovascular Sciences, University College London, 5 University Street, London, WC1E 6JF, UK
2
University College London Hospitals, 250 Euston Road, London, NW1 2PG, UK
3
Division of Surgery and Interventional Sciences, University College London, 21 University Street, London, WC1E 6AU, UK
4
Department of Cardiology, Royal Free hospital, London, NW3 2QG, UK
*
Author to whom correspondence should be addressed.
Received: 29 January 2019 / Revised: 12 March 2019 / Accepted: 4 April 2019 / Published: 9 April 2019
(This article belongs to the Section Vascular Medicine)
PDF [619 KB, uploaded 9 April 2019]

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; 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. Prostacyclin mimetics exposure to non-target IP receptors may underpin some AEs reported.
Keywords: pulmonary arterial hypertension; prostacyclin; IP receptor; treprostinil; selexipag; iloprost; beraprost; adverse events; meta-analysis pulmonary arterial hypertension; prostacyclin; IP receptor; treprostinil; selexipag; iloprost; beraprost; adverse events; meta-analysis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Picken, C.; Fragkos, K.C.; Eddama, M.; Coghlan, G.; Clapp, L.H. Adverse Events of Prostacyclin Mimetics in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis. J. Clin. Med. 2019, 8, 481.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
J. Clin. Med. EISSN 2077-0383 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top