TY - JOUR
T1 - Efficacy and safety of the endothelin-1 receptor antagonist macitentan in epicardial and microvascular vasospasm; a proof-of-concept study
AU - Feenstra, Rutger G. T.
AU - Jansen, Tijn P. J.
AU - Matthijs Boekholdt, S.
AU - Brouwer, Janet E.
AU - Klees, Margriet I.
AU - Appelman, Yolande
AU - Wittekoek, Marianne E.
AU - van de Hoef, Tim P.
AU - de Winter, Robbert J.
AU - Piek, Jan J.
AU - Damman, Peter
AU - Beijk, Marcel A. M.
N1 - Funding Information: The VERA trial is an investigator-initiated clinical trial. This study was financially sponsored by Janssen-Cilag B.V.. Actelion Pharmaceuticals Nederland B.V. has provided the investigational medicinal product. Funding Information: Declaration of Competing Interest Outside of the submitted work the authors disclose the following: P.D. has received consultancy fees from Philips and Abbott and research grants from Philips and Abbott. J.P. has received consultancy fees form Philips. Publisher Copyright: © 2023 The Author(s)
PY - 2023/8/1
Y1 - 2023/8/1
N2 - 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 Registration https://trialsearch.who.int/, Identifier: EUCTR2018-002623-42-NL. Registration date: 20 February 2019.
AB - 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 Registration https://trialsearch.who.int/, Identifier: EUCTR2018-002623-42-NL. Registration date: 20 February 2019.
KW - Coronary artery spasm
KW - Macitentan
KW - Microvascular angina
KW - Proof of concept
KW - Vasospastic angina
UR - http://www.scopus.com/inward/record.url?scp=85166635667&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ijcha.2023.101238
DO - https://doi.org/10.1016/j.ijcha.2023.101238
M3 - Article
C2 - 37576078
SN - 2352-9067
VL - 47
JO - International journal of cardiology. Heart & vasculature
JF - International journal of cardiology. Heart & vasculature
M1 - 101238
ER -