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Switching Ticagrelor to 600 Mg Or 300 Mg Clopidogrel Loading Bridge in Patients with Unstable Angina

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Switching Ticagrelor to 600 Mg Or 300 Mg Clopidogrel Loading Bridge in Patients with Unstable Angina Journal of Clinical Medicine Article Switching Ticagrelor to 600 mg or 300 mg Clopidogrel Loading Bridge in Patients with Unstable Angina Sinem Cakal 1,* , Beytullah Cakal 2, Zafer Güven 2, Aydın Rodi Tosu 1, Muhsin Kalyoncuoglu 1 , Halil Ibrahim Biter 1, Ziya Apaydın 1 , Ibrahim Oguz Karaca 2, Erdal Belen 1 and Mehmet Mustafa Can 1 1 Cardiology Department, Haseki Training and Research Hospital, University of Health Sciences, 34668 Istanbul, Turkey; [email protected] (A.R.T.); [email protected] (M.K.); [email protected] (H.I.B.); [email protected] (Z.A.); [email protected] (E.B.); [email protected] (M.M.C.) 2 Cardiology Department, Istanbul Medipol University, 34513 Istanbul, Turkey; [email protected] (B.C.); [email protected] (Z.G.); [email protected] (I.O.K.) * Correspondence: [email protected]; Tel.: +90-505755-17-70; Fax: +90-212453-20-00 Abstract: Ticagrelor is believed to be a more potent and faster antiplatelet agent compared with clopidogrel and may result in lower ischemic outcomes in patients with acute coronary syndrome. However, the best strategy of switching from ticagrelor to clopidogrel is unclear. Current guidelines advocate clopidogrel bridging with a 600 mg loading dose (LD). This study aimed to compare the safety and feasibility of switching protocols from ticagrelor to clopidogrel 600 mg or 300 mg LD in patients with unstable angina pectoris (USAP). One hundred and eighty patients with USAP undergoing adhoc percutaneous coronary intervention (PCI) received preprocedural ticagrelor 180 mg/daily. The decision to switch antiplatelet therapy to clopidogrel with either 300 mg LD or Citation: Cakal, S.; Cakal, B.; Güven, 600 mg LD at 12 h was left to the discretion of the treating physician. The primary outcome was Z.; Tosu, A.R.; Kalyoncuoglu, M.; a composite of an efficacy endpoint major adverse cardiac and cerebrovascular events (MACCEs) Biter, H.I.; Apaydın, Z.; Karaca, I.O.; and a safety endpoint Bleeding Academic Research Consortium scale (BARC) (≥1). There were no Belen, E.; Can, M.M. Switching Ticagrelor to 600 mg or 300 mg differences in our composite clinical endpoint of MACCE between the two strategies, with one event Clopidogrel Loading Bridge in occurring in each group. One patient in each group had myocardial infarction due to stent thrombosis, Patients with Unstable Angina. J. Clin. and the patient in the 300 mg switching group died due to stent thrombosis. No difference between Med. 2021, 10, 2463. https:// the two arms was observed in terms of BARC bleeding criteria. This study showed that among USAP doi.org/10.3390/jcm10112463 patients undergoing PCI, switching to clopidogrel with 300 mg LD showed no significant difference compared to 600 mg clopidogrel LD. Ticagrelor LD in ad hoc PCI and de-escalation to clopidogrel Academic Editor: Victor Serebruany with 300 mg LD could translate to lower costs for patients with USAP without compromising safety and efficacy. Received: 25 March 2021 Accepted: 27 May 2021 Keywords: switching protocols; coronary artery disease; de-escalation; unstable angina; antiplatelet Published: 2 June 2021 agent; vascular disease Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- 1. Introduction iations. Dual antiplatelet therapy (DAPT) with potent P2Y12 inhibitors on top of aspirin reduces ischemic events in patients following acute coronary syndrome (ACS). DAPT with novel P2Y12 inhibitors may reduce the risk of stent thrombosis at the expense of increased bleeding risk after coronary stenting [1]. Clopidogrel served as a cornerstone of DAPT for Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. decades despite some potential limitations such as being a pro-drug with a short-lived This article is an open access article active metabolite, relatively mild potency, slow onset of action, and a large interpatient distributed under the terms and variability of antiplatelet response [2]. conditions of the Creative Commons Ticagrelor, known as a member of a new chemical class, cyclopentyl triazolopyrim- Attribution (CC BY) license (https:// idine, acts as a direct, oral, reversibly binding P2Y12 inhibitor with a plasma half-life of creativecommons.org/licenses/by/ about 12 h [3]. In the PLATO trial, patients with moderate/high-risk ACS without ST 4.0/). segment elevation (NSTE-ACS) or ST segment elevation myocardial infarction (STEMI) J. Clin. Med. 2021, 10, 2463. https://doi.org/10.3390/jcm10112463 https://www.mdpi.com/journal/jcm J. Clin. Med. 2021, 10, x FOR PEER REVIEW 2 of 8 about 12 h [3]. In the PLATO trial, patients with moderate/high-risk ACS without ST seg- J. Clin. Med. 2021, 10, 2463 2 of 8 ment elevation (NSTE-ACS) or ST segment elevation myocardial infarction (STEMI) planned for primary PCI received clopidogrel 75 mg daily. They had a loading dose (LD) of 300–600 mg, or ticagrelor 180 mg LD followed by 90 mg twice daily. Ticagrelor was supeplannedrior to forclopidogrel primary PCI in ACS received patients clopidogrel regarding 75 mg death daily. from They vascular had a loading causes, dose myocardial (LD) of 300–600 mg, or ticagrelor 180 mg LD followed by 90 mg twice daily. Ticagrelor was infarction, or stroke without an increase in the rate of overall major bleeding [4]. superior to clopidogrel in ACS patients regarding death from vascular causes, myocardial infarction,Based on or the stroke 2017 without ESC DAPT an increase guidelines, in the rate ticagrelor of overall administration major bleeding [4(180]. mg LD, 90 mg tabletBased twice on thea day 2017) or ESC clopidogrel DAPT guidelines, instead ticagrelor of ticagrelor administration (600 mg LD (180, mg75 mg LD, daily 90 mg dose) shouldtablet be twice considered a day) or clopidogrelin patients insteadwith NSTE of ticagrelor-ACS undergoing (600 mg LD, 75PCI mg [ daily5]. However, dose) should a signif- icantbe proportion considered inof patientspatients with are switched NSTE-ACS back undergoing to clopidogrel PCI [5]. mostly However, because a significant of the need for proportionoral anticoagulation, of patients are increased switched bleeding back to clopidogrel risk, patient mostly preferences, because of thethe needpresence for oral of side effectsanticoagulation,, and socio-economic increased bleedingreasons. risk, Moreover patient, preferences,more than the14 percent presence of of patients side effects, treated withand ticagrelor socio-economic may develop reasons. dyspnea, Moreover, which more may than warrant 14 percent disco ofntinuation patients treated due to with intoler- ticagrelor may develop dyspnea, which may warrant discontinuation due to intolerance [6]. ance [6]. The appropriate approach to escalate from clopidogrel to ticagrelor is the only The appropriate approach to escalate from clopidogrel to ticagrelor is the only switch switchbetween between P2Y12 P2Y12 inhibitors inhibitors that has that been has investigated been investigated in a systematic in a systematic review and review meta- and metaanalysis-analysis powered powered for clinical for clinical endpoint endpoint (Figure (Figure1)[7]. 1) [7]. FigureFigure 1. Algorithm 1. Algorithm for switching for switching between between oral oral P2Y12 P2Y12 inhibitors inhibitors in in the the acute acute setting. LDLD == loadingloading dose. dose. Color-coding Color-coding refers refers to the ESCto theClasses ESC Classesof Recommendations: of Recommendations: green green = Class = Class I; orange I; orange = Class = Class IIb IIb(ESC (ESC Dual Dual Antiplatelet Antiplatelet Therapy Therapy Guidelines Guidelines 2017).2017). CurrentCurrently,ly, reliable reliable evidence evidence regarding the the optimal optimal dose dose approach approach of switching of switching from from ticagrelorticagrelor to toclopidogrel clopidogrel is is unclear. unclear. Considering Considering such such an obvious gapgap for for defining defining opti- optimal mal loading, some prefer a higher-dose regimen (600 mg clopidogrel bolus at the time loading, some prefer a higher-dose regimen (600 mg clopidogrel bolus at the time of the of the switch). In contrast, others consider 300 mg clopidogrel would be sufficient. We switchsought). In to contrast, evaluate others safety andconsider efficacy 300 of mg giving clopidogrel 600 mg bolus would versus be sufficient 300 mg bolus. We clopi- sought to evaluatedogrel safety in patients and withefficacy unstable of giving angina 600 (USAP) mg bolus who need versus to de-escalate 300 mg bolus from clopidogrel ticagrelor in patientsto clopidogrel. with unstable angina (USAP) who need to de-escalate from ticagrelor to clopidogrel. 2. Materials and Methods 2. MaterialsThe present and Methods study was a retrospective cohort study conducted in two centers in Istanbul, Turkey. One hundred and eighty patients with USAP undergoing ad hoc PCI pre- The present study was a retrospective cohort study conducted in two centers in Is- procedural ticagrelor 180 mg LD between November 2019 and December 2020. Unstable tanbul,angina Turkey was defined. One hundred as typical and chest eighty pain at patients rest or minimal with USAP exertion undergoing leading to ad myocardial hoc PCI pre- proceduralischemia ticagrelor without cardiomyocyte 180 mg LD between damage andNovember no persistent 2019 ST-segmentand December elevation 2020. (ECG Unstable angichanges,na was includingdefined as persistent typical chest or transient pain at ST-segmentrest or minimal depression, exertion T-wave leading inversion to
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