Thromb Haemost 2018; 118(09): 1656-1667
DOI: 10.1055/s-0038-1667337
Atherosclerosis and Ischaemic Disease
Georg Thieme Verlag KG Stuttgart · New York

Genotype-Phenotype Association and Impact on Outcomes following Guided De-Escalation of Anti-Platelet Treatment in Acute Coronary Syndrome Patients: The TROPICAL-ACS Genotyping Substudy

Lisa Gross
1  Department of Cardiology, LMU München, Munich, Germany
,
Dietmar Trenk
2  Department of Cardiology and Angiology II, University Heart Centre Freiburg, University of Freiburg, Bad Krozingen, Germany
,
Claudius Jacobshagen
3  Department of Cardiology and Pneumology, Heart Centre, Georg-August-University Göttingen, Göttingen, Germany
,
Anne Krieg
1  Department of Cardiology, LMU München, Munich, Germany
,
Meinrad Gawaz
4  Department of Cardiology and Cardiovascular Disease, University Hospital Tübingen, University of Tübingen, Tübingen, Germany
,
Steffen Massberg
1  Department of Cardiology, LMU München, Munich, Germany
5  DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
,
Monika Baylacher
1  Department of Cardiology, LMU München, Munich, Germany
,
Daniel Aradi
6  Heart Centre Balatonfüred and Heart and Vascular Centre, Semmelweis University, Budapest, Hungary
,
Fabian Stimpfle
4  Department of Cardiology and Cardiovascular Disease, University Hospital Tübingen, University of Tübingen, Tübingen, Germany
,
Julia Hromek
2  Department of Cardiology and Angiology II, University Heart Centre Freiburg, University of Freiburg, Bad Krozingen, Germany
,
Anja Vogelgesang
3  Department of Cardiology and Pneumology, Heart Centre, Georg-August-University Göttingen, Göttingen, Germany
,
Martin Hadamitzky
7  Department of Radiology, Deutsches Herzzentrum München, Technical University of Munich, München, Germany
,
Dirk Sibbing*
1  Department of Cardiology, LMU München, Munich, Germany
5  DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
,
Tobias Geisler*
4  Department of Cardiology and Cardiovascular Disease, University Hospital Tübingen, University of Tübingen, Tübingen, Germany
› Author Affiliations
Funding TROPICAL-ACS is an independent, investigator-initiated trial with an academic sponsor (Klinikum der Universität München). The trial was financially supported by a research grant from Roche Diagnostics (Rotkreuz, Switzerland) and a research grant from the German Centre for Cardiovascular Research (DZHK). Prasugrel purchase, drug delivery and related logistics were kindly supported by Eli Lilly and Company and Daiichi Sankyo Company. Funders of this study had no role in study design, collection of data and data analysis, or writing of the manuscript.
Further Information

Publication History

06 May 2018

21 June 2018

Publication Date:
13 August 2018 (eFirst)

Abstract

Background Phenotype-guided de-escalation (PGDE) of P2Y12-inhibitor treatment with an early switch from prasugrel to clopidogrel was identified as an effective alternative treatment strategy in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). The Testing Responsiveness to Platelet Inhibition on Chronic Antiplatelet Treatment for Acute Coronary Syndromes (TROPICAL-ACS) Genotyping Substudy aimed to investigate whether CYP2C19 genotypes correlate with on-treatment platelet reactivity (PR) in ACS patients treated with clopidogrel or prasugrel and thus might be useful for guidance of early de-escalation of anti-platelet treatment.

Methods and Results A total of 603 ACS consecutive patients were enrolled in four centres (23.1% of the overall TROPICAL-ACS population). Rapid genotyping (Spartan RX) for CYP2C19*2, *3 and *17 alleles was performed. Associations between PR and the primary and secondary endpoints of the TROPICAL-ACS trial and CYP2C19*2 and CYP2C19*17 carrier status were evaluated.

For the PGDE group, the on-clopidogrel PR significantly differed across CYP2C19*2 (p < 0.001) and CYP2C19*17 genotypes (p = 0.05). Control group patients were not related (p = 0.90, p = 0.74) to on-prasugrel PR. For high PR versus non-high PR patients within the PGDE group, significant differences were observed for the rate of CYP2C19*2 allele carriers (43% vs. 28%, p = 0.007).

ConclusionCYP2C19*2 and CYP2C19*17 carrier status correlates with PR in ACS patients treated with clopidogrel and thus might be useful for pre-selecting patients who will and who may not be suitable for PGDE of anti-platelet treatment. Regarding phenotype-guided treatment, we did not observe added benefit of genotyping to predict ischaemic and bleeding risk in patients who underwent a PGDE approach.

Clinical Trial Registration URL: https//www.clinicaltrials.gov. Unique Identifier: NCT: 01959451.

* Dirk Sibbing and Tobias Geisler are senior authors who contributed equally to the work.