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; Dietmar Trenk; Claudius Jacobshagen; Anne Krieg; Meinrad Gawaz; Steffen Massberg; Monika Baylacher; Daniel Aradi; Fabian Stimpfle; Julia Hromek; Anja Vogelgesang; Martin Hadamitzky; Dirk Sibbing; Tobias Geisler

doi:10.1055/s-0038-1667337

Thrombosis and Haemostasis, Inhaltsverzeichnis

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

¹Department of Cardiology, LMU München, Munich, Germany

,

Dietmar Trenk

²Department of Cardiology and Angiology II, University Heart Centre Freiburg, University of Freiburg, Bad Krozingen, Germany

,

Claudius Jacobshagen

³Department of Cardiology and Pneumology, Heart Centre, Georg-August-University Göttingen, Göttingen, Germany

,

Anne Krieg

¹Department of Cardiology, LMU München, Munich, Germany

,

Meinrad Gawaz

⁴Department of Cardiology and Cardiovascular Disease, University Hospital Tübingen, University of Tübingen, Tübingen, Germany

,

Steffen Massberg

¹Department of Cardiology, LMU München, Munich, Germany

⁵DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany

,

Monika Baylacher

¹Department of Cardiology, LMU München, Munich, Germany

,

Daniel Aradi

⁶Heart Centre Balatonfüred and Heart and Vascular Centre, Semmelweis University, Budapest, Hungary

,

Fabian Stimpfle

⁴Department of Cardiology and Cardiovascular Disease, University Hospital Tübingen, University of Tübingen, Tübingen, Germany

,

Julia Hromek

²Department of Cardiology and Angiology II, University Heart Centre Freiburg, University of Freiburg, Bad Krozingen, Germany

,

Anja Vogelgesang

³Department of Cardiology and Pneumology, Heart Centre, Georg-August-University Göttingen, Göttingen, Germany

,

Martin Hadamitzky

⁷Department of Radiology, Deutsches Herzzentrum München, Technical University of Munich, München, Germany

,

Dirk Sibbing^*

¹Department of Cardiology, LMU München, Munich, Germany

⁵DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany

,

Tobias Geisler^*

⁴Department of Cardiology and Cardiovascular Disease, University Hospital Tübingen, University of Tübingen, Tübingen, Germany

› Institutsangaben

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).

Conclusion CYP2C19*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.

Keywords

acute coronary syndrome - genotyping - platelets - thrombosis - bleeding - cytochrome P450 (CYP) 2C19

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