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      Antiplatelet Therapy Changes for Patients With Myocardial Infarction With Recurrent Ischemic Events: Insights Into Contemporary Practice From the TRANSLATE‐ACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) Study

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          Abstract

          Background

          Guidelines recommend P2Y 12 inhibitor therapy for 1 year after myocardial infarction ( MI), yet little guidance is provided on antiplatelet management for patients with recurrent ischemic events during that year. We describe changes in P2Y 12 inhibitor type among patients with recurrent ischemic events in the first year after MI.

          Methods and Results

          The TRANSLATEACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) study enrolled 12 365 patients with MI treated with percutaneous coronary intervention. We examined whether P2Y 12 inhibitor choice changed among patients with recurrent MI, stent thrombosis, and/or unplanned revascularization during the first year after MI, and modeled factors associated with P2Y 12 inhibitor intensification (changing clopidogrel to prasugrel or ticagrelor). In the first year after MI, 1414 patients (11%) had a total of 1740 recurrent ischemic events (771 recurrent MIs, 969 unplanned revascularizations, and 165 stent thromboses). Median time to the first recurrent ischemic event was 154 days (25th–75th percentiles, 55–287 days). Of those with recurrent ischemic events, 101 of 1092 (9.3%) occurring in clopidogrel‐treated patients led to P2Y 12 inhibitor intensification. Recurrent events involving stent thrombosis or MI were the strongest factors associated with P2Y 12 inhibitor intensification, yet only 40% of patients with stent thrombosis and 14% of patients with recurrent MI had P2Y 12 inhibitor intensification. Increasing age and longer time from the index MI were associated with lower likelihood for intensification.

          Conclusions

          Few patients after MI with a recurrent ischemic event who were taking clopidogrel switched to a more potent P2Y 12 inhibitor, even after stent thrombosis events. Specific guidance is needed for patients who have recurrent ischemic events, particularly when closely spaced.

          Clinical Trial Registration

          URL: https://www.clinicaltrials.gov. Unique identifier: NCT01088503.

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          Most cited references25

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          Bedside monitoring to adjust antiplatelet therapy for coronary stenting.

          Patients' responses to oral antiplatelet therapy are subject to variation. Bedside monitoring offers the opportunity to improve outcomes after coronary stenting by individualizing therapy. We randomly assigned 2440 patients scheduled for coronary stenting at 38 centers to a strategy of platelet-function monitoring, with drug adjustment in patients who had a poor response to antiplatelet therapy, or to a conventional strategy without monitoring and drug adjustment. The primary end point was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization 1 year after stent implantation. For patients in the monitoring group, the VerifyNow P2Y12 and aspirin point-of-care assays were used in the catheterization laboratory before stent implantation and in the outpatient clinic 2 to 4 weeks later. In the monitoring group, high platelet reactivity in patients taking clopidogrel (34.5% of patients) or aspirin (7.6%) led to the administration of an additional bolus of clopidogrel, prasugrel, or aspirin along with glycoprotein IIb/IIIa inhibitors during the procedure. The primary end point occurred in 34.6% of the patients in the monitoring group, as compared with 31.1% of those in the conventional-treatment group (hazard ratio, 1.13; 95% confidence interval [CI], 0.98 to 1.29; P=0.10). The main secondary end point, stent thrombosis or any urgent revascularization, occurred in 4.9% of the patients in the monitoring group and 4.6% of those in the conventional-treatment group (hazard ratio, 1.06; 95% CI, 0.74 to 1.52; P=0.77). The rate of major bleeding events did not differ significantly between groups. This study showed no significant improvements in clinical outcomes with platelet-function monitoring and treatment adjustment for coronary stenting, as compared with standard antiplatelet therapy without monitoring. (Funded by Allies in Cardiovascular Trials Initiatives and Organized Networks and others; ARCTIC ClinicalTrials.gov number, NCT00827411.).
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            Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study.

            Dual antiplatelet therapy (DAPT) cessation increases the risk of adverse events after percutaneous coronary intervention (PCI). Whether risk changes over time, depends on the underlying reason for DAPT cessation, or both is unknown. We assessed associations between different modes of DAPT cessation and cardiovascular risk after PCI. The PARIS (patterns of non-adherence to anti-platelet regimens in stented patients) registry is a prospective observational study of patients undergoing PCI with stent implantation in 15 clinical sites in the USA and Europe between July 1, 2009, and Dec 2, 2010. Adult patients (aged 18 years or older) undergoing successful stent implantation in one or more native coronary artery and discharged on DAPT were eligible for enrolment. Patients were followed up at months 1, 6, 12, and 24 after implantation. Prespecified categories for DAPT cessation included physician-recommended discontinuation, brief interruption (for surgery), or disruption (non-compliance or because of bleeding). All adverse events and episodes of DAPT cessation were independently adjudicated. Using Cox models with time-varying covariates, we examined the effect of DAPT cessation on major adverse events (MACE [composite of cardiac death, definite or probable stent thrombosis, myocardial infarction, or target-lesion revascularisation]). Incidence rates for DAPT cessation and adverse events were calculated as Kaplan-Meier estimates of time to the first event. This study is registered with ClinicalTrials.gov, number NCT00998127. We enrolled 5031 patients undergoing PCI, including 5018 in the final study population. Over 2 years, the overall incidence of any DAPT cessation was 57·3%. Rate of any discontinuation was 40·8%, of interruption was 10·5%, and of disruption was 14·4%. The corresponding overall 2 year MACE rate was 11·5%, most of which (74%) occurred while patients were taking DAPT. Compared with those on DAPT, the adjusted hazard ratio (HR) for MACE due to interruption was 1·41 (95% CI 0·94-2·12; p=0·10) and to disruption was 1·50 (1·14-1.97; p=0·004). Within 7 days, 8-30 days, and more than 30 days after disruption, adjusted HRs were 7·04 (3·31-14·95), 2·17 (0·97-4·88), and 1·3 (0·97-1·76), respectively. By contrast with patients who remained on DAPT, those who discontinued had lower MACE risk (0·63 [0·46-0·86]). Results were similar after excluding patients receiving bare metal stents and using an alternative MACE definition that did not include target lesion revascularisation. In a real-world setting, for patients undergoing PCI and discharged on DAPT, cardiac events after DAPT cessation depend on the clinical circumstance and reason for cessation and attenuates over time. While most events after PCI occur in patients on DAPT, early risk for events due to disruption is substantial irrespective of stent type. Bristol-Myers Squibb and Sanofi-Aventis. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              A randomized trial of prasugrel versus clopidogrel in patients with high platelet reactivity on clopidogrel after elective percutaneous coronary intervention with implantation of drug-eluting stents: results of the TRIGGER-PCI (Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel) study.

              This study sought to investigate the efficacy, safety, and antiplatelet effect of prasugrel as compared with clopidogrel in patients with high on-treatment platelet reactivity (HTPR) after elective percutaneous coronary intervention (PCI). The extent to which prasugrel can correct HTPR and improve clinical outcomes in patients undergoing elective PCI is unknown. Stable coronary artery disease (CAD) patients with HTPR (>208 P2Y(12) reaction units [PRU] by the VerifyNow test) after elective PCI with at least 1 drug-eluting stent (DES) were randomly assigned to either prasugrel 10 mg daily or clopidogrel 75 mg daily. Platelet reactivity of the patients on the study drug was reassessed at 3 and 6 months. The study was stopped prematurely for futility because of a lower than expected incidence of the primary endpoint. In 212 patients assigned to prasugrel, PRU decreased from 245 (225 to 273) (median [interquartile range]) at baseline to 80 (42 to 124) at 3 months, whereas in 211 patients assigned to clopidogrel, PRU decreased from 249 (225 to 277) to 241 (194 to 275) (p < 0.001 vs. prasugrel). The primary efficacy endpoint of cardiac death or myocardial infarction at 6 months occurred in no patient on prasugrel versus 1 on clopidogrel. The primary safety endpoint of non-coronary artery bypass graft Thrombolysis In Myocardial Infarction major bleeding at 6 months occurred in 3 patients (1.4%) on prasugrel versus 1 (0.5%) on clopidogrel. Switching from clopidogrel to prasugrel in patients with HTPR afforded effective platelet inhibition. However, given the low rate of adverse ischemic events after PCI with contemporary DES in stable CAD, the clinical utility of this strategy could not be demonstrated. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                alexander.fanaroff@duke.edu
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                08 February 2018
                February 2018
                : 7
                : 4 ( doiID: 10.1002/jah3.2018.7.issue-4 )
                : e007982
                Affiliations
                [ 1 ] Division of Cardiology Duke University Durham NC
                [ 2 ] Duke Clinical Research Institute Duke University Durham NC
                [ 3 ] Division of Cardiology University of Massachusetts Medical Center Worcester MA
                [ 4 ] Division of Cardiology John Ochsner Heart and Vascular Institute New Orleans LA
                [ 5 ] Division of Cardiology Cedars‐Sinai Heart Institute Los Angeles CA
                Author notes
                [*] [* ] Correspondence to: Alexander Fanaroff, MD, Duke Clinical Research Institute, 2400 Pratt St, Durham, NC 27710. E‐mail: alexander.fanaroff@ 123456duke.edu
                Article
                JAH32948
                10.1161/JAHA.117.007982
                5850204
                29437596
                c2bc412d-5867-4925-8250-0dc34b282346
                © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 30 October 2017
                : 08 January 2018
                Page count
                Figures: 3, Tables: 2, Pages: 11, Words: 8331
                Funding
                Funded by: Daiichi Sankyo, Inc,
                Categories
                Original Research
                Original Research
                Coronary Heart Disease
                Custom metadata
                2.0
                jah32948
                February 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.2.2 mode:remove_FC converted:20.02.2018

                Cardiovascular Medicine
                clopidogrel,coronary revascularization,myocardial infarction,secondary prevention,stent thrombosis,quality and outcomes,cardiovascular disease,revascularization

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