The safety and effectiveness of bivalirudin in female patients with acute myocardial infarction undergoing primary angioplasty: A subgroup analysis of the BRIGHT trial.
Liang Zhenyang,Li Yi,Wang Jingping,Wang Dongmei,Wang Shouli,Ma Likun,Liu Huiliang,Yang Lixia,Stone Gregg W,Han Yaling
Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions
BACKGROUND:Being female is an independent predictor of adverse events during percutaneous coronary interventions (PCI). OBJECTIVE:To evaluate the safety and efficiency of bivalirudin during emergency PCI in female patients with acute myocardial infarction (AMI). METHODS:The present study was a subgroup analysis of the randomized Bivalirudin in Acute Myocardial Infarction vs. Heparin and GPI plus Heparin (BRIGHT) trial. A total of 392 female patients enrolled in the BRIGHT trial were assigned to receive bivalirudin with post-procedure dose infusion (n = 127) or heparin with or without tirofiban (n = 265). The primary efficiency endpoint was 30-day net adverse clinical events (NACEs). The secondary efficiency endpoints were 30-day major cardiac and cerebral events (MACCEs) and bleeding events defined according to Bleeding Academic Research Consortium (BARC) definitions. RESULTS:For female patients, bivalirudin treatment was associated with significantly lower incidences of 30-day NACEs (6.3% vs. 21.5%, P < 0.001), any bleeding (2.4% vs. 12.8%, P = 0.001) and BARC 2-5 type bleeding (1.6% vs. 7.2%, P = 0.021) compared with the control regimen. The incidence of MACCEs (3.4% vs. 9.4%, P = 0.055) and stent thrombosis (0% vs. 1.1%, P = 0.229) were comparable between the two groups. Multivariate analysis showed that bivalirudin (OR: 0.245, 95% CI: 0.113-0.532, P < 0.001), transradial access (OR: 0.119, 95% CI: 0.067-0.211, P < 0.001), and statin (OR: 0.254, 95% CI: 0.08-0.807, P = 0.02) were independent protective factors for 30-day NACEs in female patients. CONCLUSIONS:The use of bivalirudin during emergency PCI for AMI in female patients significantly reduced the bleeding risk with anticoagulation effects compared with heparin with or without tirofiban.
[A large-scale, multicenter, retrospective study on efficacy of bivalirudin use during peri-percutaneous coronary intervention period for Chinese patients with coronary heart disease].
Han Y L,Chen Y D,Jiang T M,Ge J B,Cheng X S,Li J L,Chen Y G,Ma Y T,Xie Q,Ma L K,Zheng X Q,Yang B S,Chen S L,Wang G,Zhao X,Liu H W,Liang Z Y,Liu M L,Wang H Y,Li Y
Zhonghua xin xue guan bing za zhi
OBJECTIVE:To observe the efficacy and safety of bivalirudin use in Chinese patients with coronary heart disease (CHD) during the peri-percutaneous coronary intervention(PCI) period. METHODS:A total of 3 271 patients who underwent PCI and received periprocedural bivalirudin treatment between July 2013 and October 2015 from 88 centers of China were involved in this study. The primary outcome was 30-day net adverse clinical events (NACE a composite of major adverse cardiac or cerebral events (MACE, all-cause death, reinfarction, urgent target vessel revascularization, or stroke) or bleeding), the secondary outcome was stent thrombosis at 30 days. RESULTS:The mean age of enrolled patients was (65.12±12.44) years old, 27.4%(889/3 244) of them were female. Percent of stable coronary disease (SCD), non-ST segment elevation acute coronary syndrome (NSTE-ACS) and ST elevation myocardial infarction (STEMI) was 5.0%(162/3 248), 44.6%(1 450/3 248) and 50.4%(1 636/3 248) respectively. Radial access was performed in 89.5% (2 879/3 271) patients, and 9.7% (316/3 271) and 34.1% (1 115/3 271) patients also received ticagrelor and tirofiban medication. 69.3% (2 266/3 271) patients received post-procedural bivalirudin infusion, in which 46.3% (1 050/2 266) was treated at PCI-does, with a median duration of 2.5(1.0, 4.0) h. During the 30-day follow-up, NACE occurred in 3.45% (103/2 988) patients, the incidence of MACE, death was 2.17% (65/2 994) and 1.03% (31/3 017), respectively and bleeding events were recorded in 1.37% (41/2 996) patients. Four cases (0.13%) of stent thrombosis (3 acute stent thrombosis) were recorded. CONCLUSION:Peri-PCI Bivalirudin use is safe and related with low bleeding risk in Chinese CHD patients.
No association between on-treatment platelet reactivity and bleeding events following percutaneous coronary intervention and antiplatelet therapy: A post hoc analysis.
Nishikawa Masakatsu,Isshiki Takaaki,Kimura Takeshi,Ogawa Hisao,Yokoi Hiroyoshi,Miyazaki Shunichi,Ikeda Yasuo,Nakamura Masato,Takita Atsushi,Saito Shigeru,
INTRODUCTION:Few studies have examined the relationship between the pharmacodynamics of antiplatelet drugs and the risk of clinically significant bleeding following percutaneous coronary intervention (PCI) for treating acute coronary syndrome (ACS). We examined the associations between the pharmacodynamics of prasugrel and clopidogrel and the incidence of bleeding events in the acute and chronic phases after PCI. MATERIALS AND METHODS:We performed a post hoc analysis of the PRASFIT-ACS (PRASugrel compared with clopidogrel For Japanese patIenTs with ACS undergoing PCI) study of patients in whom platelet reactivity was determined as P2Y12 reaction units (PRU; VerifyNow® P2Y12 assay) or vasodilator-stimulated phosphoprotein-phosphorylation reactivity index (VASP-PRI). Japanese patients were randomized to prasugrel (loading/maintenance dose: 20/3.75 mg) or clopidogrel (300/75 mg), both in combination with aspirin, for 24-48 weeks. The bleeding outcome was a composite of major, minor, and clinically relevant bleeding. RESULTS:Overall, 66/685 (9.6%) and 65/678 (9.6%) of prasugrel- and clopidogrel-treated patients, respectively, experienced major, minor, or clinically relevant bleeding. PRU and VASP-PRI at 5-12h or in steady state conditions (at 4 weeks) were not associated with the risk of bleeding in the acute (to day 3) or chronic (from day 4 to 14 days after treatment discontinuation) phases of treatment, respectively. Less than 9% of patients with low on-treatment platelet reactivity (defined as PRU<85 or VASP-PRI<16) experienced bleeding events. CONCLUSION:No direct association of the pharmacodynamics of prasugrel and clopidogrel with the risk of bleeding was observed in this cohort of Japanese ACS patients following PCI.
The impact of unfractionated heparin or bivalirudin on patients with stable coronary artery disease undergoing percutaneous coronary intervention.
Lima Fabio V,Gruberg Luis,Aslam Usman,Ramgadoo Melissa,Clase Kydanis,Trevisan Alessandra,Jeremias Allen
Journal of interventional cardiology
OBJECTIVES:To compare bleeding and clinical events of patients with stable angina or silent ischemia undergoing percutaneous coronary intervention (PCI) treated with unfractionated heparin (UFH) or bivalirudin. BACKGROUND:Few direct comparisons between UFH monotherapy versus bivalirudin exist for patients with stable ischemic heart disease undergoing PCI. METHODS:A prospective, investigator-initiated, single-center, single-blinded, randomized trial of UFH versus bivalirudin was conducted. The primary endpoint was all bleeding (major and minor) from index-hospitalization to 30 days post discharge. Secondary endpoints included major adverse cerebral and cardiovascular events (MACCE) and net adverse clinical events (NACE). RESULTS:Two-hundred-sixty patients were randomized for treatment with either UFH (n = 123) (47%) or bivalirudin (n = 137) (53%) There were no significant differences in baseline clinical and angiographic characteristics between the two groups. Primary endpoint was similar in both groups (10.9% with bivalirudin vs 7.3% with UFH [P = 0.31]). Major bleeding rates were 5.8% and 2.4%, respectively (P = 0.17). There was a higher MACCE (3.5% vs 0%, P = 0.03) and NACE (8.8% vs 2.4%, P = 0.03) rate with bivalirudin compared to UFH, respectively. Bivalirudin had increased odds of NACE (OR = 3.65, 95% CI: 1.00-13.3.6). Death and stent thrombosis rates were low and similar in both groups. Radial access was associated with fewer bleeding events compared to femoral access but not statistically significant (P = 0.29). CONCLUSIONS:Among patients with stable angina or silent ischemia, there was no difference between UFH and bivalirudin in bleeding rates up to 30-days post-PCI. MACCE and NACE were higher among the bivalirudin group. Radial access was associated with a numerically lower rate of bleeding compared with femoral access.
Effect of postprocedural full-dose infusion of bivalirudin on acute stent thrombosis in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: Outcomes in a large real-world population.
Wang Heyang,Liang Zhenyang,Li Yi,Li Bin,Liu Junming,Hong Xueyi,Lu Xin,Wu Jiansheng,Zhao Wei,Liu Qiang,An Jian,Li Linfeng,Pu Fanli,Ming Qiang,Han Yaling
AIM:This study aimed to evaluate the effect of prolonged full-dose bivalirudin infusion in real-world population with ST-elevation myocardial infarction (STEMI). BACKGROUND:Subgroup data as well as meta-analysis from randomized clinical trials have shown the potency of postprocedural full-dose infusion (1.75 mg/kg/h) of bivalirudin on attenuating acute stent thrombosis (ST) after primary percutaneous coronary intervention (PCI). METHODS:In this multicenter retrospective observational study, 2047 consecutive STEMI patients treated with bivalirudin during primary PCI were enrolled in 65 Chinese centers between July 2013 and May 2016. The primary outcome was acute ST defined as ARC definite/probable within 24 hours after the index procedure, and the secondary endpoints included total ST, major adverse cardiac or cerebral events (MACCE, defined as death, reinfarction, stroke, and target vessel revascularization), and any bleeding at 30 days. RESULTS:Among 2047 STEMI patients, 1123 (54.9%) were treated with postprocedural bivalirudin full-dose infusion (median 120 minutes) while the other 924 (45.1%) received low-dose (0.25 mg/kg/h) or null postprocedural infusion. A total of three acute ST (0.3%) occurred in STEMI patients with none or low-dose prolonged infusion of bivalirudin, but none was observed in those treated with post-PCI full-dose infusion (0.3% vs 0.0%, P=.092). Outcomes on MACCE (2.1% vs 2.7%, P=.402) and total bleeding (2.1% vs 1.4%, P=.217) at 30 days showed no significant difference between the two groups, and no subacute ST was observed. CONCLUSION:Post-PCI full-dose bivalirudin infusion is safe and has a trend to protect against acute ST in STEMI patients undergoing primary PCI in real-world settings.
Bivalirudin vs heparin with or without tirofiban during primary percutaneous coronary intervention in acute myocardial infarction: the BRIGHT randomized clinical trial.
Han Yaling,Guo Jincheng,Zheng Yang,Zang Hongyun,Su Xi,Wang Yu,Chen Shaoliang,Jiang Tiemin,Yang Ping,Chen Jiyan,Jiang Dongju,Jing Quanmin,Liang Zhenyang,Liu Haiwei,Zhao Xin,Li Jing,Li Yi,Xu Bo,Stone Gregg W,
IMPORTANCE:The safety and efficacy of bivalirudin compared with heparin with or without glycoprotein IIb/IIIa inhibitors in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are uncertain. OBJECTIVE:To determine if bivalirudin is superior to heparin alone and to heparin plus tirofiban during primary PCI. DESIGN, SETTING, AND PARTICIPANTS:Multicenter, open-label trial involving 2194 patients with AMI undergoing primary PCI at 82 centers in China between August 2012 and June 2013. INTERVENTIONS:Patients were randomly assigned to receive bivalirudin with a post-PCI infusion (n = 735), heparin alone (n = 729), or heparin plus tirofiban with a post-PCI infusion (n = 730). Among patients treated with bivalirudin, a postprocedure 1.75 mg/kg/h infusion was administered for a median of 180 minutes (IQR, 148-240 minutes). MAIN OUTCOMES AND MEASURES:The primary end point was 30-day net adverse clinical events, a composite of major adverse cardiac or cerebral events (all-cause death, reinfarction, ischemia-driven target vessel revascularization, or stroke) or bleeding. Additional prespecified safety end points included the rates of acquired thrombocytopenia at 30 days, and stent thrombosis at 30 days and 1 year. RESULTS:Net adverse clinical events at 30 days occurred in 65 patients (8.8%) of 735 who were treated with bivalirudin compared with 96 patients (13.2%) of 729 treated with heparin (relative risk [RR], 0.67; 95% CI, 0.50-0.90; difference, -4.3%, 95% CI, -7.5% to -1.1%; P = .008); and 124 patients (17.0%) of 730 treated with heparin plus tirofiban (RR for bivalirudin vs heparin plus tirofiban, 0.52; 95% CI, 0.39-0.69; difference, -8.1%, 95% CI, -11.6% to -4.7%; P < .001). The 30-day bleeding rate was 4.1% for bivalirudin, 7.5% for heparin, and 12.3% for heparin plus tirofiban (P < .001). There were no statistically significant differences between treatments in the 30-day rates of major adverse cardiac or cerebral events (5.0% for bivalirudin, 5.8% for heparin, and 4.9% for heparin plus tirofiban, P = .74), stent thrombosis (0.6% vs 0.9% vs 0.7%, respectively, P = .77), acquired thrombocytopenia (0.1% vs 0.7% vs 1.1%; P = .07), or in acute (<24-hour) stent thrombosis (0.3% in each group). At the 1-year follow-up, the results remained similar. CONCLUSIONS AND RELEVANCE:Among patients with AMI undergoing primary PCI, the use of bivalirudin with a median 3-hour postprocedure PCI-dose infusion resulted in a decrease in net adverse clinical events compared with both heparin alone and heparin plus tirofiban. This finding was primarily due to a reduction in bleeding events with bivalirudin, without significant differences in major adverse cardiac or cerebral events or stent thrombosis. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01696110.
Characteristics and risk factors of cerebrovascular accidents after percutaneous coronary interventions in patients with history of stroke.
Zhang Hua,Feng Li-qun,Bi Qi,Wang Yu-ping
Chinese medical journal
BACKGROUND:Percutaneous coronary intervention (PCI) is a well-established method for managing coronary diseases. However, the increasing use of PCI has led to an increased incidence of acute cerebrovascular accidents (CVA) related to PCI. In this study, we investigated the characteristics and risk factors of CVA after PCI in patients with known stroke history. METHODS:Between January 1, 2005 and March 1, 2009, 621 patients with a history of stroke underwent a total of 665 PCI procedures and were included in this retrospective study. Demographic and clinical characteristics, previous medications, procedures, neurologic deficits, location of lesion and in-hospital clinical outcomes of patients who developed a CVA after the cardiac catheterization laboratory visit and before discharge were reviewed. RESULTS:Acute CVA was diagnosed in 53 (8.5%) patients during the operation or the perioperative period. Seventeen patients suffered from transient ischemic attack, thirty-four patients suffered from cerebral infarction and two patients suffered from cerebral hemorrhage. The risk factors for CVA after PCI in stroke patients were: admission with an acute coronary syndrome, use of an intra-aortic balloon pump, urgent or emergency procedures, diabetes mellitus, and poor left ventricular systolic function, arterial fibrillation, previous myocardial infarction, dyslipidemia, tobacco use, and no/irregular use of anti-platelet medications. CONCLUSIONS:The incidence of CVA during and after PCI in patients with history of stroke is much higher than that in patients without history of stroke. Patients with atrial fibrillation, previous myocardial infarction, diabetes mellitus, dyslipidemia, tobacco use, and no or irregular use of anti-platelet medications were at higher risk for recurrent stroke. This study showed a strong association between acute coronary syndromes and in-hospital stroke after PCI.
Vasodilator-stimulated phosphoprotein-guided Clopidogrel maintenance therapy reduces cardiovascular events in atrial fibrillation patients requiring anticoagulation therapy and scheduled for percutaneous coronary intervention: a prospective cohort study.
Hu Chaoyue,Zhang Xumin,Liu Yonghua,Gao Yang,Zhao Xiaohong,Zhou Hua,Luo Yu,Liu Yaling,Wang Xiaodong
BMC cardiovascular disorders
BACKGROUND:In a previous study, we found that titrating clopidogrel maintenance doses (MDs) according to vasodilator-stimulated phosphoprotein (VASP) monitoring minimised the rate of major adverse cardiovascular and cerebral events (MACCE) after percutaneous coronary intervention (PCI) without increasing bleeding in patients with high on-treatment platelet reaction to clopidogrel. This study aimed to investigate whether VASP-guided clopidogrel MD could reduce thromboembolism and bleeding in atrial fibrillation (AF) patients requiring anticoagulation and scheduled for PCI. METHODS:AF patients scheduled for PCI were recruited between July 2014 and July 2016. These patients were allocated into VASP-guided (n = 250) and control (n = 253) groups depending on the clopidogrel MD profile. In the VASP-guided group, clopidogrel MD was titrated by the platelet reactivity index (PRI), whereas in the control group, clopidogrel MD was fixed at 75 mg per day. The primary endpoint was MACCE and secondary endpoints were thrombolysis in myocardial infarction (TIMI) major and minor bleeding 1 year after PCI. RESULTS:Five hundred and three patients were included in the present study, with 1-year data available for 95.6% patients. The average CHADS-VASc score of the whole population was 3.7 ± 0.7 and the average HAS-BLED score was 3.2 ± 0.4. MACCE was less in the VASP-guided group than in the control group (2.5% vs. 5.0%, P = 0.02). The incidence of major bleeding was comparable between both groups (3.0% vs. 2.8%, P = 0.72) and minor bleeding was higher in the VASP-guided group than in the control group (15.3% vs. 9.7%, P = 0.03). Kaplan-Meier analysis indicated that there was no difference in survival between both groups (log-rank test, P = 0.68). CONCLUSIONS:In AF patients requiring anticoagulation and scheduled for PCI, VASP-guided antiplatelet therapy reduced major cardiovascular and cerebral adverse events, accompanied by increased minor bleeding events. TRIAL REGISTRATION:The present study was retrospectively registered in the Chinese Clinical Trial Registry, A Primary Registry of the International Clinical Trial Registry Platform, World Health Organisation (Registration no: ChiCTR-IOR-17013854 ). The registered date was December 11, 2117.
Duration and clinical outcome of dual antiplatelet therapy after percutaneous coronary intervention: a retrospective cohort study using a medical information database from Japanese hospitals.
Cardiovascular intervention and therapeutics
In this real-world, retrospective cohort study of 9753 patients in Japan prescribed dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI), we investigated DAPT duration and determined factors associated with early DAPT discontinuation and with event rates in patients who discontinued DAPT. The study period was April 1, 2012-March 31, 2018; endpoints comprised composite efficacy [death, myocardial infarction (MI), and stroke] and bleeding (intracranial, gastrointestinal, and requiring transfusion) endpoints. Overall, 68.8% of patients were continuing DAPT at 3 months post-PCI. Patients without major efficacy or safety events within 3 months after index PCI were included in a landmark analysis set (LAS; n = 7056), and categorized as DAPT ≥ 3 months (continuation) versus < 3 months (discontinuation). In the two LAS analysis groups, there was no difference in the composite bleeding endpoint (P = 0.067), although the incidence of the composite efficacy endpoint was higher in the discontinuation group (P < 0.001). In multivariate regression analysis, age ≥ 75 years, minor bleeding after PCI, history of cerebral infarction, history of cerebral or gastrointestinal bleeding, atrial fibrillation, dialysis, and anticoagulant use after PCI were associated with early DAPT discontinuation. Acute coronary syndrome, history of MI, kidney disorder, and anticoagulant use after PCI were associated with the composite efficacy endpoint in the discontinuation group. In conclusion, early DAPT discontinuation is more likely in patients at high bleeding risk, but may influence the occurrence of ischemic events in these patients. Determination of DAPT duration should take into account potential ischemic risk, even in patients at high bleeding risk.
Successful Percutaneous Balloon Angioplasty in a Patient Presenting With STEMI and Acute Intracranial Hemorrhage.
Obagi Aref,Schoenfeld Matthew
Percutaneous coronary interventions (PCI) mandates the administration of anti-platelet and anti-thrombotic agents to prevent intracoronary and post-procedural thrombosis upon introducing thrombogenic foreign bodies such as intracoronary wires, balloons, or stents, especially in the setting of acute coronary syndrome (ACS) given the hypercoagulable state associated with it. This is a case of a 54-year-old female who presented to the emergency department with left-sided weakness and dysarthria for an unknown duration. A CT scan of the head showed acute right middle cerebral artery distribution infarct. She subsequently underwent a successful thrombectomy. Four hours later, the patient became lethargic and nauseous. Electrocardiogram showed anterior wall ST elevation with new-onset anterior wall akinesia on transthoracic echocardiogram. Repeat CT of the head showed acute intracranial hemorrhagic conversion. She then developed cardiac arrest mandating emergent cardiac catheterization. Coronary angiogram revealed 100% occlusion in a mid left anterior descending artery (LAD) and 80% in a left circumflex artery (LCX) and chronic total occlusion of the right coronary artery (RCA). After weighing risks and benefits, PCI was performed with rapid plain old balloon angioplasty (POBA) to the 100% thrombotic lesion in the LAD with successful restoration of flow without administering anti-platelet or anti-thrombotic agents given the acute intracranial hemorrhage, She was then discharged to a rehab facility a few days later in stable condition. This case demonstrates successful percutaneous coronary intervention in the 100% occluded LAD in a life-threatening situation despite not using anticoagulation or antiplatelet therapy due to active intracranial hemorrhage.
Dual Antiplatelet Therapy after PCI in Patients at High Bleeding Risk.
Valgimigli Marco,Frigoli Enrico,Heg Dik,Tijssen Jan,Jüni Peter,Vranckx Pascal,Ozaki Yukio,Morice Marie-Claude,Chevalier Bernard,Onuma Yoshinobu,Windecker Stephan,Tonino Pim A L,Roffi Marco,Lesiak Maciej,Mahfoud Felix,Bartunek Jozef,Hildick-Smith David,Colombo Antonio,Stanković Goran,Iñiguez Andrés,Schultz Carl,Kornowski Ran,Ong Paul J L,Alasnag Mirvat,Rodriguez Alfredo E,Moschovitis Aris,Laanmets Peep,Donahue Michael,Leonardi Sergio,Smits Pieter C,
The New England journal of medicine
BACKGROUND:The appropriate duration of dual antiplatelet therapy in patients at high risk for bleeding after the implantation of a drug-eluting coronary stent remains unclear. METHODS:One month after they had undergone implantation of a biodegradable-polymer sirolimus-eluting coronary stent, we randomly assigned patients at high bleeding risk to discontinue dual antiplatelet therapy immediately (abbreviated therapy) or to continue it for at least 2 additional months (standard therapy). The three ranked primary outcomes were net adverse clinical events (a composite of death from any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (a composite of death from any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding; cumulative incidences were assessed at 335 days. The first two outcomes were assessed for noninferiority in the per-protocol population, and the third outcome for superiority in the intention-to-treat population. RESULTS:Among the 4434 patients in the per-protocol population, net adverse clinical events occurred in 165 patients (7.5%) in the abbreviated-therapy group and in 172 (7.7%) in the standard-therapy group (difference, -0.23 percentage points; 95% confidence interval [CI], -1.80 to 1.33; P<0.001 for noninferiority). A total of 133 patients (6.1%) in the abbreviated-therapy group and 132 patients (5.9%) in the standard-therapy group had a major adverse cardiac or cerebral event (difference, 0.11 percentage points; 95% CI, -1.29 to 1.51; P = 0.001 for noninferiority). Among the 4579 patients in the intention-to-treat population, major or clinically relevant nonmajor bleeding occurred in 148 patients (6.5%) in the abbreviated-therapy group and in 211 (9.4%) in the standard-therapy group (difference, -2.82 percentage points; 95% CI, -4.40 to -1.24; P<0.001 for superiority). CONCLUSIONS:One month of dual antiplatelet therapy was noninferior to the continuation of therapy for at least 2 additional months with regard to the occurrence of net adverse clinical events and major adverse cardiac or cerebral events; abbreviated therapy also resulted in a lower incidence of major or clinically relevant nonmajor bleeding. (Funded by Terumo; MASTER DAPT ClinicalTrials.gov number, NCT03023020.).