Refereed journal article or data article (A1)

Safety and efficacy of the 5-lipoxygenase-activating protein inhibitor AZD5718 in patients with recent myocardial infarction: The phase 2a FLAVOUR study




List of Authors: Prescott E, Angerås O, Erlinge D, Grove EL, Hedman M, Jensen L, Pernow J, Saraste A, Åkerblom A, Svedlund S, Rudvik A, Knöchel J, Lindstedt EL, Garkaviy P, Gan LM, Gabrielsen A

Publisher: ELSEVIER IRELAND LTD

Publication year: 2022

Journal: International Journal of Cardiology

Journal name in source: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

Journal acronym: INT J CARDIOL

Volume number: 365

Number of pages: 1

ISSN: 0735-1097

eISSN: 1874-1754

DOI: http://dx.doi.org/10.1016/j.ijcard.2022.07.016

URL: https://doi.org/10.1016/j.ijcard.2022.07.016

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/176381722


Abstract

Background: Leukotrienes are pro-inflammatory vasoactive lipid mediators implicated in the pathophysiology of atherosclerotic cardiovascular disease. We studied the effect of the 5-lipoxygenase-activating protein inhibitor AZD5718 on leukotriene biosynthesis and coronary microvascular function in a single-blind, phase 2a study.

Methods: Patients 7–28 days after myocardial infarction (±ST elevation), with <50% left anterior descending
coronary artery stenosis and Thrombolysis in Myocardial Infarction flow grade ≥ 2 after percutaneous coronary intervention, were randomized 2:1:2 to once-daily AZD5718 200 mg or 50 mg, or placebo, in 4- and 12-week cohorts. Change in urine leukotriene E4 (uLTE4) was the primary endpoint, and coronary flow velocity reserve (CFVR; via echocardiography) was the key secondary endpoint.

Results: Of 129 randomized patients, 128 received treatment (200 mg, n = 52; 50 mg, n = 25; placebo, n = 51). Statistically significant reductions in uLTE4 levels of >80% were observed in both AZD5718 groups versus the placebo group at 4 and 12 weeks. No significant changes in CFVR were observed for AZD5718 versus placebo. Adverse events (AEs) occurred in 12/18, 3/6 and 6/13 patients receiving 200 mg, 50 mg and placebo, respectively, in the 4-week cohort, and in 27/34, 14/19 and 24/38 patients, respectively, in the 12-week cohort. Serious AEs in seven patients receiving AZD5718 and four receiving placebo were not treatment-related, and there were no deaths.


Downloadable publication

This is an electronic reprint of the original article.
This reprint may differ from the original in pagination and typographic detail. Please cite the original version.




Last updated on 2022-03-10 at 15:20