Safety and efficacy of the 5-lipoxygenase-activating protein inhibitor AZD5718 in patients with recent myocardial infarction : The phase 2a FLAVOUR study
(2022) In International Journal of Cardiology 365. p.34-40- 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... (More)
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. Conclusions: In patients with recent myocardial infarction, AZD5718 was well tolerated, and leukotriene biosynthesis was dose-dependently inhibited. No significant changes in CFVR were detected. ClinicalTrials.gov identifier: NCT03317002.
(Less)
- author
- organization
- publishing date
- 2022-10-15
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- 5-Lipoxygenase activating protein, Cardiovascular disease, Leukotriene, Randomized clinical trial
- in
- International Journal of Cardiology
- volume
- 365
- pages
- 7 pages
- publisher
- Elsevier
- external identifiers
-
- scopus:85135496051
- pmid:35842004
- ISSN
- 0167-5273
- DOI
- 10.1016/j.ijcard.2022.07.016
- language
- English
- LU publication?
- yes
- id
- 904efdbc-f84e-4780-9ff1-d854f408ec55
- date added to LUP
- 2022-11-29 13:51:07
- date last changed
- 2024-09-17 07:54:44
@article{904efdbc-f84e-4780-9ff1-d854f408ec55, abstract = {{<p>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 E<sub>4</sub> (uLTE<sub>4</sub>) 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 uLTE<sub>4</sub> 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. Conclusions: In patients with recent myocardial infarction, AZD5718 was well tolerated, and leukotriene biosynthesis was dose-dependently inhibited. No significant changes in CFVR were detected. ClinicalTrials.gov identifier: NCT03317002.</p>}}, author = {{Prescott, Eva and Angerås, Oskar and Erlinge, David and Grove, Erik L. and Hedman, Marja and Jensen, Lisette O. and Pernow, John and Saraste, Antti and Åkerblom, Axel and Svedlund, Sara and Rudvik, Anna and Knöchel, Jane and Lindstedt, Eva Lotte and Garkaviy, Pavlo and Gan, Li Ming and Gabrielsen, Anders}}, issn = {{0167-5273}}, keywords = {{5-Lipoxygenase activating protein; Cardiovascular disease; Leukotriene; Randomized clinical trial}}, language = {{eng}}, month = {{10}}, pages = {{34--40}}, publisher = {{Elsevier}}, series = {{International Journal of Cardiology}}, title = {{Safety and efficacy of the 5-lipoxygenase-activating protein inhibitor AZD5718 in patients with recent myocardial infarction : The phase 2a FLAVOUR study}}, url = {{http://dx.doi.org/10.1016/j.ijcard.2022.07.016}}, doi = {{10.1016/j.ijcard.2022.07.016}}, volume = {{365}}, year = {{2022}}, }