Dual Antiplatelet Therapy De-escalation Strategies

Dual antiplatelet therapy (DAPT), the combination of aspirin (ASA), and a P2Y12 inhibitor, protects against stent thrombosis new atherothrombotic events after implantation or an acute coronary syndrome, but exposes patients to increased risk bleeding. In most current practices, inhibitor is stopped at 6 12 months ASA continued indefinitely. The advent safer stents, with less thrombosis, has challenged this standard care, however. A number alternative strategies involving earlier de-escalation have therefore been proposed. these approaches, DAPT switched potent antithrombotic time-point than recommended by guidelines. Three different variations tested date. first one maintains switches from inhibitors ticagrelor prasugrel either lower dose clopidogrel, while maintaining ASA. 2 other approaches involve changing single some percutaneous intervention procedure, stopping These all demonstrated benefit in clinical trials so far, especially contribution secondary prevention clearly evolving as its role increasing bleeding complications not providing ischemic becoming more clear. contemporary practice, type duration should now be based on individualized decision, strategies, if used wisely, can added existing options. After (PCI) syndrome (ACS), require dual (DAPT) minimize events. usually consists low-dose (ASA) clopidogrel stable artery disease (CAD) ACS. default guideline-recommended length PCI for CAD months, least ACS, although longer durations considered high shorter those risk.1Valgimigli M Bueno H Byrne RA Collet JP Costa F Jeppsson Juni P Kastrati Kolh Mauri L Montalescot G Neumann FJ Petricevic Roffi Steg PG Windecker S Zamorano JL Levine GN Group ESCSD, Guidelines ESCCfP, Societies ESCNC2017 ESC focused update developed collaboration EACTS: Task Force European Society Cardiology (ESC) Association Cardio-Thoracic Surgery (EACTS).Eur Heart J. 2018; 39: 213-260Crossref PubMed Scopus (1464) Google Scholar,2Levine Bates ER Bittl JA Brindis RG Fihn SD Fleisher LA Granger CB Lange Mack MJ Mehran R Mukherjee D Newby LK O'Gara PT Sabatine MS Smith PK SC 2016 ACC/AHA guideline disease.J Am Coll Cardiol. 2016; 68: 1082-1115Crossref (856) Scholar At time-points, practice discontinued, rationale behind continuing only that thrombotic intervention, decreases afterwards. downside DAPT, however, it With stents implanting techniques, focus shifted keeping low, rather vice versa. Stents biocompatible (or no) polymers, antiproliferative drugs thinner struts. process re-endothelialization largely completed within few protecting stented segment thereafter. addition, platforms improved, making drug-eluting (DES) much deliver. Implanting techniques help intracoronary imaging modalities also optimized, intent thrombosis. Even so, DES, remains necessary without indication oral anticoagulation. Although clear periprocedural absolutely essential,3Kenaan Seth Aronow HD Wohns Share Gurm HS. outcomes performed pre-procedural aspirin.J 2013; 62: 2083-2089Crossref (15) interventional therapies thus made straightforward decide what subsequent strategy be, how long maintained. As become over years serious minor contribute events, de-escalating What common “de-escalated” date, will form review (Figure 1). landmark subanalyses Platelet inhibition patient Outcomes (PLATO) Trial Assess Improvement Therapeutic Optimizing Inhibition Prasugrel-Thrombolysis Myocardial Infarction suggest reducing occurs early ACS.4Antman EM Wiviott Murphy SA Voitk J Hasin Y Widimsky Chandna Macias W McCabe CH Braunwald E. Early late benefits syndromes undergoing intervention: TRITON-TIMI 38 (TRial InhibitioN Infarction) analysis.J 2008; 51: 2028-2033Crossref (278) Scholar,5Becker RC Bassand Budaj Wojdyla DM James SK Cornel JH French Held C Horrow Husted Lopez-Sendon Lassila Mahaffey KW Storey RF Harrington Wallentin L. Bleeding receptor antagonists PLATelet trial.Eur 2011; 32: 2933-2944Crossref (268) Consequently, risk, makes sense downgrade phase. De-escalation done switching their normal lower, dose, ASA, selecting platelet function genetic testing. study was open label single-center timing (TOPIC) study, which examined impact planned default, unguided 1 month 2).6Cuisset T Deharo Quilici Johnson TW Deffarges Bassez Bonnet Fourcade Mouret Lambert Verdier V Morange PE Alessi MC JL. Benefit syndrome: TOPIC (timing syndrome) randomized study.Eur 2017; 38: 3070-3078Crossref (211) 646 ACS who underwent remained adverse procedure same switch clopidogrel. dosing changed. primary end point, net composite cardiovascular death (CVD), urgent revascularization, stroke BARC classification ?2 year significantly arm (13.4%) continuation (26.3%, hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.34 0.68). This difference seemed mainly driven too small draw general conclusions, no observed. Another approach limiting guide choice between versus patient's response Indeed, sufficient under might extra protection provided inhibitor. Such guidance testing Testing Responsiveness To On Chronic Antiplatelet Treatment For Acute Coronary Syndromes (TROPICAL-ACS) genotype-guided prediction POPular-Genetics Tailored Initiation Lessen due Decreased Clopidogrel Response Percutaneous Intervention (TAILOR-PCI). open-label TROPICAL-ACS 2,610 platelet-function guided strategy.7Sibbing Aradi Jacobshagen Gross Trenk Geisler Orban Hadamitzky Merkely B Kiss Komocsi Dezsi CA Holdt Felix SB Parma Klopotowski Schwinger RHG Rieber Huber K Koltowski Mehilli Huczek Z Massberg Investigators T-A.Guided treatment (TROPICAL-ACS): randomised, open-label, multicentre trial.Lancet. 390: 1747-1757Abstract Full Text PDF (288) All received week (10 5 mg) followed then test; were kept whereas (39%) back prasugrel. CVD, myocardial infarction (MI), stroke, bleeding, (noninferiority p = 0.004). rates individual points low arms. Given absence reduction both major unclear such multiple revisit could apart cost. are fact de-escalated event, sufficiently safe very risk. genotyping presence gene variants poor 2,488 ticagrelor, CYP2C19-genotype-guided approach.8Claassens DMF Vos GJA Bergmeijer TO Hermanides RS van 't Hof AWJ der Harst Barbato E Morisco Tjon Joe Gin RM Asselbergs FW Mosterd Herrman JR Dewilde WJM Janssen PWA Kelder JC Postma de Boer Boersma Deneer VHM Ten berg JM. PCI.N Engl Med. 2019; 381: 1621-1631Crossref (203) arm, *2 *3 loss-of alleles gene; noncarriers (61%), carriers treated (39%). co-primary all-cause death, MI, PLATO-defined combined point similar strategies: 5.1% 5.9% <0.001). Major (9.8%) (12.5%, HR 0.78, CI 0.61 0.98). entirely fewer arm. TAILOR-PCI study.9Pereira NL Farkouh ME So Lennon Geller N Mathew Bell Bae Jeong MH Chavez I Gordon Abbott JD Cagin Baudhuin Fu YP Goodman SG Hasan Iturriaga Lerman Sidhu Tanguay JF Wang Weinshilboum Welsh Rosenberg Bailey Rihal C. Effect selection vs conventional trial.JAMA. 2020; 324: 761-771Crossref (87) Here, aim test among loss-of-function allele carriers. Post-PCI (n 5,302, 82% ACS) escalation 12-month clopidogrel-based months. severe recurrent ischemia numerically group statistically strategies. Among carriers, rate 4.0% (HR 0.66, 0.43 1.02). Thrombolysis (TIMI) occurred infrequently extent groups. Based results studies, hence seems avoid when ticagrelor-based reduce escalating DAPT. An easy point-of-care CYP2C19 available provides result hour, costs kits acquisition analysis equipment prohibitive healthcare systems affluent regions any event would overall cost strategy. final practical option decrease PCI. recent HOST-REDUCE trial. trial, 2,338 10 mg month. Most eligible repeat class 2–5 year, frequently (7.2%) (10.1%, 0.70, 0.52 0.92). halved 0.32 0.73), completely (BARC 2) bleedings. Ischemic East Asian population, whether pertain western population prone events.10Onuma Kimura Räber Magro Girasis Domburg Mitsudo Serruys PW. Differences factors, procedural characteristics, mortality two all-comers registries Europe Japan: patient-level data Bern-Rotterdam j-Cypher registries.EuroIntervention. 2015; 11: 533-540PubMed Still, decreasing beyond phase may promising need further study. de-escalate monotherapy relatively 3 studies DES 3). DAPT-STEMI, event-free 870) additional 6-month period.11Kedhi Fabris Ent Buszman von Birgelen Roolvink Zurakowski Schotborgh CE Hoorntje JCA Eek Cook Togni Meuwissen Royen Vliet Wedel Delewi Zijlstra F. Six ST-elevation (DAPT-STEMI): multicentre, non-inferiority trial.Bmj. 363: k3793Crossref (69) PCI, TIMI groups: 4.8% 6.6% up 0.73, 0.41 1.27, noninferiority More half revascularization procedures, precluding conclusion low-risk patients. second REDUCE, 1,496 3-month regimen successful placement.12De Luca Damen Camaro Benit Verdoia Rasoul Liew HB Polad Ahmad WA Zambahari Kedhi Suryapranata H. Final randomised evaluation short-term new-generation (REDUCE trial).EuroIntervention. 15: e990-e998Crossref (53) Only 60% discharged ticagrelor. target vessel 2, 3, 5) arms (8.2% 8.4% m m, <0.001) 24 (11.6% 12.1%, different, higher onward (3.1% 2.2% 0.27). There twice many alone (12 6). Finally, SMART-DATE compared 2,712 implantation.13Hahn JY Song YB Oh Cho DK Lee JB Doh Kim SH JO BO Suh IW DI Park HK JS Choi WG WS KH TK JM Yang Gwon HC. (SMART-DATE): 391: 1274-1284Abstract (142) MI 18 groups (4.7% 6-m 4.2% ?12-m, 0.03). frequent regimen: 1.8% 0.8% ?12-m 2.41, 1.15 5.05). Stent well (15 10). 2-5) (2.7% 3.9% 0.09). Taken together, do really support systematic, DES. still warranted supported comparing BMS populations.14Urban Meredith IT Abizaid Pocock SJ Carrie Naber Lipiecki Richardt Iniguez Brunel Valdes-Chavarri Garot Talwar Berland Abdellaoui Eberli Oldroyd Gregson Greene Stoll HP Morice Polymer-free Drug-Coated risk.N 373: 2038-2047Crossref (536) Scholar,15Varenne O Sideris Kedev Cuisset Hovasse El Mahmoud Spaulding Helft Diaz Fernandez Brugaletta Pinar-Bermudez Ferre Commeau Teiger Bogaerts Sabate Sinnaeve PR Drug-eluting elderly (SENIOR): single-blind 41-50Abstract (218) Registries daily practice.16Claeys Beauloye Pourbaix Rewinder Study G. 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Effects hemostatic system activation: trial healthy subjects.J Thromb Haemost. 14: 273-281Crossref (27) because activation critical step thromboxane A2-mediated aggregation vitro, does seem block inhibitor.19Armstrong PC Leadbeater PD Chan MV Kirkby NS Jakubowski Mitchell Warner TD. strong blockade, little aggregation.J 9: 552-561Crossref (115) Scholar,20Baber U Zafar MU Dangas Escolar Angiolillo DJ Sharma Kini AS Sartori Joyce Vogel Farhan Gurbel Gibson CM Fuster Badimon JJ. Ticagrelor pci: TWILIGHT substudy.J 75: 578-586Crossref (29) Moreover, even hypothesized actually increase off-target cyclo-oxygenase inhibition.21Warner TD Armstrong Curzen NP JA. disease: antagonists?.Heart. 2010; 96: 1693-1694Crossref (43) consequence, discontinuation, phase, compromising Five far strategy, moderate-sized Asia (Comparison Between Antagonist Monotherapy Therapy (SMART-CHOICE), Short Optimal Duration Everolimus-Eluting Cobalt-Chromium Stent-2 (STOPDAPT-2) Without Aspirin Syndrome (TICO)) large international (GLOBAL LEADERS: Clinical Comparing Two Forms Anti-platelet Implantation (GLOBAL-LEADERS) Alone High-Risk Patients (TWILIGHT)) STOPDAPT-2 3,045) SMART-CHOICE 2,993) respectively, (clopidogrel (nonrandomized) SMART-CHOICE).22Hahn Chun WJ YH Jang Im ES BR Yun Koh YY JW Yoon HJ SU Rha SW 321: 2428-2437Crossref (224) Scholar,23Watanabe Domei Morimoto Natsuaki Shiomi Toyota Ohya Suwa Takagi Nanasato Hata Yagi Suematsu Yokomatsu Takamisawa Doi Noda Okayama Seino Tada Sakamoto Hibi Abe Kawai Nakao Ando Tanabe Ikari Hanaoka KI Morino Kozuma Kadota Furukawa Nakagawa T. 1-month receiving PCI: 2414-2427Crossref (313) TICO 3,056 plus year.24Kim BK Hong Her AY Jeon DW Yoo SY Kwon Shin DH Nam Ko YG MK Y. 323: 2407-2416Crossref (100) TICO, investigators chose endpoint combining included target-vessel revascularization. incidence (3.9% 5.9%, 0.91). 1.3% absolute 0.56, appeared excess arm; 4