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Abstract
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).
- coronary artery disease
- spasm
- coronary stenting
- beta blockers
- calcium channel blockers
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Twitter @MitsuakiSawano
MS, TK and SK contributed equally.
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.
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.
Patient consent for publication Not required.
Ethics approval The institutional review boards at each participating hospital approved the trial protocol: Keio University Hospital, Kobe City Medical Center General Hospital, Nishinomiya Watanabe Cardiovascular Center, Tokyo Bay Urayasu Ichikawa Medical Center, National Hospital Organization Tokyo Medical Center and Saiseikai Central Hospital.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available according to the 'Act on the Protection of Personal Information' Law (as of May 2017) and the 'Ethical Guidelines for Medical and Health Research Involving Human Subjects' (as of March 2015). The current study data were obtained from the JCD-KiCS PCI registry and are available upon request to The Institutional Review Board of Keio University School of Medicine (med-rinri-jimu@adst.keio.ac.jp).