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P2Y12 Inhibitor Switching in Response to Routine Notification of CYP2C19 Clopidogrel Metabolizer Status Following Acute Coronary Syndromes.

dc.contributor.author Povsic, Thomas
dc.contributor.author Roe, Matthew
dc.contributor.author Ohman, Erik
dc.contributor.author Rockhold, Frank
dc.contributor.author White, Jennifer
dc.contributor.author Montalescot, Gilles
dc.contributor.author Cornel, Jan H
dc.contributor.author Nicolau, Jose C
dc.contributor.author Steg, P Gabriel
dc.contributor.author James, Stefan
dc.contributor.author Bode, Christoph
dc.contributor.author Welsh, Robert C
dc.contributor.author Plotnikov, Alexei N
dc.contributor.author Mundl, Hardi
dc.contributor.author Gibson, C Michael
dc.date.accessioned 2019-08-14T02:57:19Z
dc.date.available 2019-08-14T02:57:19Z
dc.date.issued 2019-07
dc.identifier.issn 2380-6583
dc.identifier.issn 2380-6591
dc.identifier.uri https://hdl.handle.net/10161/19189
dc.description.abstract Importance:Physician behavior in response to knowledge of a patient's CYP2C19 clopidogrel metabolizer status is unknown. Objective:To investigate the association of mandatory reporting of CYP2C19 pharmacogenomic testing, provided to investigators with no direct recommendations on how to use these results, with changes in P2Y12 inhibitor use, particularly clopidogrel, in the Randomized Trial to Compare the Safety of Rivaroxaban vs Aspirin in Addition to Either Clopidogrel or Ticagrelor in Acute Coronary Syndrome (GEMINI-ACS-1) clinical trial. Design, Setting, and Participants:The GEMINI-ACS-1 trial compared rivaroxaban, 2.5 mg twice daily, with aspirin, 100 mg daily, plus open-label clopidogrel or ticagrelor (provided), in patients with recent acute coronary syndromes (ACS). The trial included 371 clinical centers in 21 countries and 3037 patients with ACS. Data were analyzed between May 2017 and February 2019. Interventions:Investigators were required to prestipulate their planned response to CYP2C19 metabolizer status. In response to a regulatory mandate, results for all patients were reported to investigators approximately 1 week after randomization. Main Outcomes and Measures:Reasons for switching P2Y12 inhibitors and occurrence of bleeding and ischemic events were collected. Results:Of 3037 patients enrolled (mean [SD] age, 62.8 [9.0] years; 2275 men [74.9%], and 2824 white race/ethnicity [93.0%]), investigators initially treated 1704 (56.1%) with ticagrelor and 1333 (43.9%) with clopidogrel. Investigators prestipulated that they would use CYP2C19 metabolizer status to change P2Y12 inhibitor in 48.5% of genotyped clopidogrel-treated patients (n = 642 of 1324) and 5.5% of genotyped ticagrelor-treated patients (n = 93 of 1692). P2Y12 inhibitor switching for any reason occurred in 197 patients and was more common in patients treated with ticagrelor (146 of 1704 [8.6%]) compared with clopidogrel (51 of 1333 [3.8%]). Of patients initially treated with ticagrelor, only 1 (0.1% overall; 0.7% of all who switched) was switched based on CYP2C19 status. Of patients initially treated with clopidogrel, 23 (1.7% overall,;45.1% of all who switched) were switched owing to metabolizer status. Of 48 patients (3.6%) with reduced metabolizer status treated initially with clopidogrel, 15 (31.3%) were switched based on metabolizer status, including 48.1% (13 of 27) in which switching was prestipulated. Conclusions and Relevance:Physicians were evenly split on how to respond to knowledge of CYP2C19 metabolizer status in clopidogrel-treated patients. Mandatory provision of this information rarely prompted P2Y12 inhibitor switching overall, including a minority of patients with reduced metabolizer status. These findings highlight the clinical equipoise among physicians regarding use of this information and the reluctance to use information from routine genotyping in the absence of definitive clinical trial data demonstrating the efficacy of this approach. Clinical Trial Registration:ClinicalTrials.gov identifier: NCT02293395.
dc.publisher American Medical Association (AMA)
dc.relation.ispartof JAMA cardiology
dc.relation.isversionof 10.1001/jamacardio.2019.1510
dc.subject Science & Technology
dc.subject Life Sciences & Biomedicine
dc.subject Cardiac & Cardiovascular Systems
dc.subject Peripheral Vascular Disease
dc.subject Cardiovascular System & Cardiology
dc.title P2Y12 Inhibitor Switching in Response to Routine Notification of CYP2C19 Clopidogrel Metabolizer Status Following Acute Coronary Syndromes.
dc.type Conference
duke.contributor.id Povsic, Thomas|0113224
duke.contributor.id Roe, Matthew|0079636
duke.contributor.id Ohman, Erik|0066629
duke.contributor.id Rockhold, Frank|0668002
dc.date.updated 2019-08-14T02:57:18Z
pubs.begin-page 680
pubs.end-page 684
pubs.issue 7
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Duke Clinical Research Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine, Cardiology
pubs.organisational-group Medicine
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Biostatistics & Bioinformatics
pubs.organisational-group Basic Science Departments
pubs.publication-status Published
pubs.volume 4
duke.contributor.orcid Rockhold, Frank|0000-0003-3732-4765


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