TY - JOUR
T1 - Beta blockers versus calcium channel blockers for provocation of vasospastic angina after drug-eluting stent implantation
T2 - A multicentre prospective randomised trial
AU - Sawano, Mitsuaki
AU - Katsuki, Toshiomi
AU - Kitai, Takeshi
AU - Tamita, Koichi
AU - Obunai, Kotaro
AU - Ikegami, Yukinori
AU - Yamane, Takafumi
AU - Ueda, Ikuko
AU - Endo, Ayaka
AU - Maekawa, Yuichiro
AU - Kawamura, Akio
AU - Fukuda, Keiichi
AU - Kohsaka, Shun
N1 - Funding Information:
Competing interests MS reports grants from Japan Promotional Society for Cardiovascular Disease Sakakibara Memorial Research Grant, grants from Japan Heart Foundation Japan Heart Foundation Research Grant, and grants from Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (18K17332) during the conduct of the study; grants from Takeda Pharma, Takeda Japan Medical Office Funded Research Grant 2018 outside the submitted work. TI has a research grant from Boston Scientific. SK reports investigator-initiated grant funding from Bayer and Daiichi Sankyo and personal fees from Bayer and Bristol-Myers Squibb. HI receives lecture fees from Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Chugai Pharma, Daiichi Sankyo, Otsuka Pharma, Pfizer, Mochida Pharma and MSD.
Funding Information:
catheterisation laboratories of the participating centres and the clinical research coordinators: YM, Shunsuke Yuasa, Hideaki Kanazawa, Kentaro Hayashida and Takashi Kawakami (Keio University School of Medicine); Yukihiko Momiyama, Munehisa Sakamoto, Jun Fuse, Kojiro Tanimoto, YI and Kohei Inagawa (National Hospital Organization Tokyo Medical Center). Contributors IU, AE and SK conceived and designed the research. MS and TK performed the statistical analysis. AE and SK handled funding and supervision. TK, KT, KO, YI, TY, IU, YM and AK acquired the data. MS, TK and SK drafted the manuscript. TK, YM, AK and KF made critical revision of the manuscript for key intellectual content. All authors have approved the final article. Funding This study was supported in part by the grants-in-aid from the Ministry of Health, Labour, and Welfare (Award number: 24790538) and Pfizer Japan Inc. (Tokyo, Japan; award number: 04-013-0455), based on the research contract between the company and the Keio University School of Medicine. SK has received grants from Bayer Yakuhin and Daiichi-Sankyo, lecture fees from Bayer Yakuhin and Bristol-Myers Squibb, and consulting fees from Pfizer. The equipment and drugs used in the study were purchased by the participating hospitals.
PY - 2020/10/21
Y1 - 2020/10/21
N2 - Background Drug-eluting stent-induced vasospastic angina (DES-VSA) has emerged as a novel complication in the modern era of percutaneous coronary intervention (PCI). Although beta blockers (BBs) are generally recommended for coronary heart disease, they may promote incidence of DES-VSA. This study aimed to compare the effects of calcium channel blockers (CCBs) perceived to be protective against DES-VSA and BBs on subsequent coronary events after second-generation drug-eluting stent implantation. Methods In this multicentre prospective, randomised study, 52 patients with coronary artery disease who underwent PCI for a single-vessel lesion with everolimus-eluting stent placement were randomised into post-stenting BB (N=26) and CCB (N=26) groups and followed for 24 months to detect any major cardiovascular events (MACE). A positive result on acetylcholine provocation testing during diagnostic coronary angiography (CAG) at 9 months was the primary endpoint for equivalence. MACE included all-cause death, non-fatal myocardial infarction, unstable angina, cerebrovascular disease or coronary revascularisation for stable coronary artery disease after index PCI. Results At 9 months, 42 patients (80.8%) underwent diagnostic coronary angiography and acetylcholine provocation testing. Among them, seven patients in each group were diagnosed with definite vasospasm (intention-to-treat analysis 26.9% vs 26.9%, risk difference 0 (-0.241, 0.241)). Meanwhile, the secondary endpoint, 24-month MACE, was higher in the CCB group (19.2%) than in the BB group (3.8%) (p=0.01). In detail, coronary revascularisation for stable coronary artery disease was the predominant endpoint that contributed to the greater proportion of MACE in the CCB group (CCB (19.2%) vs BB (3.8%), p=0.03). Conclusions The incidence of acetylcholine-induced coronary artery spasms did not differ between patients receiving BBs or CCBs at 9 months after PCI. However, a higher incidence of 2-year MACE was observed in the CCB group, suggesting the importance of BB administration. Trial registration number This study was registered at the Japanese University Hospital Medical Information Network (UMIN) Clinical Trial Registry (The Prospective Randomized Trial for Optimizing Medical Therapy After Stenting: Calcium-Beta Trial; UMIN000008321, https://upload.umin.ac.jp/cgi-open-bin/ctr-e/ctr-view.cgi?recptno=R000009536).
AB - Background Drug-eluting stent-induced vasospastic angina (DES-VSA) has emerged as a novel complication in the modern era of percutaneous coronary intervention (PCI). Although beta blockers (BBs) are generally recommended for coronary heart disease, they may promote incidence of DES-VSA. This study aimed to compare the effects of calcium channel blockers (CCBs) perceived to be protective against DES-VSA and BBs on subsequent coronary events after second-generation drug-eluting stent implantation. Methods In this multicentre prospective, randomised study, 52 patients with coronary artery disease who underwent PCI for a single-vessel lesion with everolimus-eluting stent placement were randomised into post-stenting BB (N=26) and CCB (N=26) groups and followed for 24 months to detect any major cardiovascular events (MACE). A positive result on acetylcholine provocation testing during diagnostic coronary angiography (CAG) at 9 months was the primary endpoint for equivalence. MACE included all-cause death, non-fatal myocardial infarction, unstable angina, cerebrovascular disease or coronary revascularisation for stable coronary artery disease after index PCI. Results At 9 months, 42 patients (80.8%) underwent diagnostic coronary angiography and acetylcholine provocation testing. Among them, seven patients in each group were diagnosed with definite vasospasm (intention-to-treat analysis 26.9% vs 26.9%, risk difference 0 (-0.241, 0.241)). Meanwhile, the secondary endpoint, 24-month MACE, was higher in the CCB group (19.2%) than in the BB group (3.8%) (p=0.01). In detail, coronary revascularisation for stable coronary artery disease was the predominant endpoint that contributed to the greater proportion of MACE in the CCB group (CCB (19.2%) vs BB (3.8%), p=0.03). Conclusions The incidence of acetylcholine-induced coronary artery spasms did not differ between patients receiving BBs or CCBs at 9 months after PCI. However, a higher incidence of 2-year MACE was observed in the CCB group, suggesting the importance of BB administration. Trial registration number This study was registered at the Japanese University Hospital Medical Information Network (UMIN) Clinical Trial Registry (The Prospective Randomized Trial for Optimizing Medical Therapy After Stenting: Calcium-Beta Trial; UMIN000008321, https://upload.umin.ac.jp/cgi-open-bin/ctr-e/ctr-view.cgi?recptno=R000009536).
KW - beta blockers
KW - calcium channel blockers
KW - coronary artery disease
KW - coronary stenting
KW - spasm
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U2 - 10.1136/openhrt-2020-001406
DO - 10.1136/openhrt-2020-001406
M3 - Article
AN - SCOPUS:85094827956
VL - 7
JO - Open Heart
JF - Open Heart
SN - 2053-3624
IS - 2
M1 - e001406
ER -