Efficacy and safety of the endothelin-1 receptor antagonist macitentan in epicardial and microvascular vasospasm; a proof-of-concept study.
| Autor: | Feenstra RGT; Amsterdam UMC, Heart Center, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands., Jansen TPJ; Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands., Matthijs Boekholdt S; Amsterdam UMC, Heart Center, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands., Brouwer JE; Amsterdam UMC, Heart Center, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands., Klees MI; Amsterdam UMC, Heart Center, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands., Appelman Y; Amsterdam UMC, Heart Center, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands., Wittekoek ME; Cardiology, HeartLife Clinics, Utrecht, the Netherlands., van de Hoef TP; Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands., de Winter RJ; Amsterdam UMC, Heart Center, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands., Piek JJ; Amsterdam UMC, Heart Center, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands., Damman P; Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands., Beijk MAM; Amsterdam UMC, Heart Center, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands. |
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| Jazyk: | angličtina |
| Zdroj: | International journal of cardiology. Heart & vasculature [Int J Cardiol Heart Vasc] 2023 Jul 16; Vol. 47, pp. 101238. Date of Electronic Publication: 2023 Jul 16 (Print Publication: 2023). |
| DOI: | 10.1016/j.ijcha.2023.101238 |
| Abstrakt: | Background: Treatment of patients diagnosed with angina due to epicardial or microvascular coronary artery spasm (CAS) is challenging because patients often remain symptomatic despite conventional pharmacological therapy. In this prospective, randomized, double-blind, placebo-controlled, sequential cross-over proof-of-concept study, we compared the efficacy and safety of macitentan, a potent inhibitor of the endothelin-1 receptor, to placebo in symptomatic patients with CAS despite background pharmacological treatment. Methods: Patients with CAS diagnosed by invasive spasm provocation testing with >3 anginal attacks per week despite pharmacological treatment were considered for participation. Participants received either 10 mg of macitentan or placebo daily for 28 days as add-on treatment. After a wash-out period patients were crossed over to the alternate treatment arm. The primary endpoint was the difference in anginal burden calculated as [1] the duration (in minutes) * severity (on a Visual Analogue Scale (VAS) pain scale 1-10); and [2] the frequency of angina attacks * severity during medication use compared to the run-in phase. Results: 28 patients of whom 22 females (79%) and a mean age of 55.3 ± 7.6 completed the entire study protocol (epicardial CAS n = 19 (68), microvascular CAS n = 9 (32)). Change in both indices of anginal burden were not different during treatment with add-on macitentan as compared to add-on placebo (duration*severity: -9 [-134 78] vs -45 [-353 11], p = 0.136 and frequency*severity: -1.7 [-5.8 1.2] vs -1.8 [-6.2 0.3], p = 0.767). The occurrence and nature of self-reported adverse events were closely similar between the treatment phase with macitentan and placebo. Conclusion: In patients with angina due to epicardial or microvascular CAS despite background pharmacological treatment, 28 days of add-on treatment with the ET-1 receptor antagonist, macitentan 10 mg daily, did not reduce anginal burden compared to add-on treatment with placebo.Trial Registrationhttps://trialsearch.who.int/, Identifier: EUCTR2018-002623-42-NL. Registration date: 20 February 2019. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2023 The Author(s).) |
| Databáze: | MEDLINE |
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