TY - JOUR
T1 - Comparison of Unguided De-Escalation Versus Guided Selection of Dual Antiplatelet Therapy After Acute Coronary Syndrome
T2 - A Systematic Review and Network Meta-Analysis
AU - Kuno, Toshiki
AU - Fujisaki, Tomohiro
AU - Shoji, Satoshi
AU - Sahashi, Yuki
AU - Tsugawa, Yusuke
AU - Iwagami, Masao
AU - Takagi, Hisato
AU - Briasoulis, Alexandros
AU - Deharo, Pierre
AU - Cuisset, Thomas
AU - Latib, Azeem
AU - Kohsaka, Shun
AU - Bhatt, Deepak L.
N1 - Funding Information:
This study was funded by the Japan Society for the Promotion of Science (grant number 20H03915).
Funding Information:
Dr Latib is a consultant for and is on the advisory board of Medtronic, Abbott, Boston Scientific, and Philips. Dr Tsugawa was supported by the NIH/National Institute on Minority Health and Health Disparities (NIMHD) grant R01MD013913 and NIH/National Institute on Aging (NIA) grant R01AG068633 for other work not related to this study. Dr Kohsaka has received an unrestricted research grant from Daiichi Sankyo. Dr Bhatt discloses the following relationships: Advisory Board: AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; Board of Directors: AngioWave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock)‚ DRS.LINQ (stock options), Society of Cardiovascular Patient Care, and TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial [Portico Re-sheathable Transcatheter Aortic Valve System US IDE Trial], funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial [Comparison Trial Evaluating Efficacy and Safety of Single i.v. Bolus Tenecteplase Plus Standard Anticoagulation as Compared With Standard Anticoagulation in Normotensive Patients]), Cleveland Clinic (including for the ExCEED trial [A Prospective, Single-Arm, Controlled, Multicenter Study to Establish the Safety and Effectiveness of the CENTERA THV System in Intermediate Risk Patients Who Have Symptomatic, Severe, Calcific, Aortic Stenosis Requiring Aortic Valve Replacement], funded by Edwards), Contego Medical (Chair, PERFORMANCE 2 [Protection Against Emboli During Carotid Artery Stenting Using a 3-in-1 Delivery System Comprised of a Post-Dilation Balloon, Integrated Embolic Filter and a Novel Carotid Stent II]), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial [Edoxaban Versus Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation - in Atrial Fibrillation], funded by Daiichi Sankyo, and for the ABILITY-DM trial [Randomized Comparison of Abluminus DES+ Sirolimus-Eluting Stents Versus Everolimus-Eluting Stents in Coronary Artery Disease Patients With Diabetes Mellitus Global - ABILITY Diabetes Global], funded by Concept Medical), Novartis, and Population Health Research Institute; Rutgers University (for the NIH-funded MINT trial [Myocardial Ischemia and Transfusion]); honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, American College of Cardiology Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI [A Prospective Randomised, Open Label, Blinded Endpoint Study to Evaluate DUAL Antithrombotic Therapy With Dabigatran Etexilate Plus Clopidogrel or Ticagrelor vs Triple Therapy Strategy With Warfarin Plus Clopidogrel or Ticagrelor and Aspirin in Patients With Non Valvular Atrial Fibrillation That Have Undergone a Percutaneous Coronary Intervention With Stenting] Clinical Trial Steering Committee funded by Boehringer Ingelheim; AEGIS-II [ApoA-I Event Reducing in Ischemic Syndromes II] Executive Committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial [A Multi-Center, Randomized, Assessor-Blind, Controlled Trial Comparing the Occurrence of Major Adverse Cardiovascular Events in Patients With Prostate Cancer and Cardiovascular Disease Receiving Degarelix or Leuprolide], funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (Continuing Medical Education [CME] steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS [A Randomized Controlled Trial of Rivaroxaban for the Prevention of Major Cardiovascular Events in Patients With Coronary or Peripheral Artery Disease] operations committee, publications committee, steering committee, and USA national coleader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), and Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor), NCDR (The National Cardiovascular Data Registry)-ACTION Registry Steering Committee (Chair), and VA CART (Veterans Affairs Clinical Assessment Reporting and Tracking) Research and Publications Committee (Chair); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, and 89Bio; royalties: Elsevier (Editor, Braunwald’s Heart Disease); site coinvestigator: Abbott, Biotronik, Boston Scientific, Cardiovascular Systems‚ Inc‚ Endotronix, St. Jude Medical (now Abbott), Philips, Svelte, and Vascular Solutions; Trustee: American College of Cardiology; and unfunded research: FlowCo and Takeda. The other authors report no conflicts.
Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/8/1
Y1 - 2022/8/1
N2 - Background: The benefit of dual antiplatelet therapy (DAPT) for reducing ischemic events is greatest in the early period of acute coronary syndrome, and recent randomized controlled trials have investigated the unguided de-escalation strategy of changing potent P2Y12inhibitors to less potent or reduced-dose P2Y12inhibitors 1 month after acute coronary syndrome. However, it remains unclear which strategy is more effective and safer: the uniform unguided de-escalation strategy versus the personalized guided selection of DAPT with genotype or platelet function tests. Methods: PubMed, EMBASE, and Cochrane Central were searched for articles published from database inception to September 10, 2021. Randomized controlled trials investigating DAPT using clopidogrel, low-dose prasugrel, standard-dose prasugrel, ticagrelor, unguided de-escalation strategy, and guided selection strategy for patients with acute coronary syndrome were included. Hazard ratios and relative risk estimates were extracted from each study. The estimates were pooled using a random-effects network meta-analysis. The primary efficacy outcome was major adverse cardiovascular events, defined as a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major or minor bleeding. Secondary outcomes were all-cause death, cardiovascular death, myocardial infarction, stroke, stent thrombosis, and major bleeding. Results: This study included 19 randomized controlled trials with 69 746 patients. Compared with guided selection of DAPT, unguided de-escalation of DAPT was associated with a decreased risk of the primary safety outcome (hazard ratio, 0.48 [95% CI, 0.33-0.72]) without increased risks of major adverse cardiovascular events (hazard ratio, 0.82 [95% CI, 0.53-1.28]) or any secondary outcomes. The results were similar when the guided selection strategy was divided into platelet function-guided and genotype-guided strategies. Conclusions: Compared with guided selection of DAPT, unguided de-escalation of DAPT decreased bleeding without increasing ischemic events in patients after acute coronary syndrome. If a strategy of de-escalation is chosen, these findings do not support the routine use of personalized guiding tests. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021273082.
AB - Background: The benefit of dual antiplatelet therapy (DAPT) for reducing ischemic events is greatest in the early period of acute coronary syndrome, and recent randomized controlled trials have investigated the unguided de-escalation strategy of changing potent P2Y12inhibitors to less potent or reduced-dose P2Y12inhibitors 1 month after acute coronary syndrome. However, it remains unclear which strategy is more effective and safer: the uniform unguided de-escalation strategy versus the personalized guided selection of DAPT with genotype or platelet function tests. Methods: PubMed, EMBASE, and Cochrane Central were searched for articles published from database inception to September 10, 2021. Randomized controlled trials investigating DAPT using clopidogrel, low-dose prasugrel, standard-dose prasugrel, ticagrelor, unguided de-escalation strategy, and guided selection strategy for patients with acute coronary syndrome were included. Hazard ratios and relative risk estimates were extracted from each study. The estimates were pooled using a random-effects network meta-analysis. The primary efficacy outcome was major adverse cardiovascular events, defined as a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major or minor bleeding. Secondary outcomes were all-cause death, cardiovascular death, myocardial infarction, stroke, stent thrombosis, and major bleeding. Results: This study included 19 randomized controlled trials with 69 746 patients. Compared with guided selection of DAPT, unguided de-escalation of DAPT was associated with a decreased risk of the primary safety outcome (hazard ratio, 0.48 [95% CI, 0.33-0.72]) without increased risks of major adverse cardiovascular events (hazard ratio, 0.82 [95% CI, 0.53-1.28]) or any secondary outcomes. The results were similar when the guided selection strategy was divided into platelet function-guided and genotype-guided strategies. Conclusions: Compared with guided selection of DAPT, unguided de-escalation of DAPT decreased bleeding without increasing ischemic events in patients after acute coronary syndrome. If a strategy of de-escalation is chosen, these findings do not support the routine use of personalized guiding tests. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021273082.
KW - acute coronary syndrome
KW - genotype
KW - percutaneous coronary intervention
KW - stents
UR - http://www.scopus.com/inward/record.url?scp=85136767417&partnerID=8YFLogxK
U2 - 10.1161/CIRCINTERVENTIONS.122.011990
DO - 10.1161/CIRCINTERVENTIONS.122.011990
M3 - Review article
C2 - 35899618
AN - SCOPUS:85136767417
SN - 1941-7640
VL - 15
SP - E011990
JO - Circulation: Cardiovascular Interventions
JF - Circulation: Cardiovascular Interventions
IS - 8
ER -