Randomised, double-blind trial on the value of tapered discontinuation of clopidogrel maintenance therapy after drug-eluting stent implantation

K. Anette Fiedler; Julinda Mehilli; Sebastian Kufner; Anna Schlichting; Tareq Ibrahim; Dirk Sibbing; Ilka Ott; Heribert Schunkert; Karl-Ludwig Laugwitz; Adnan Kastrati; Stefanie Schulz

doi:10.1160/TH13-11-0900

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2014; 111(06): 1041-1049
DOI: 10.1160/TH13-11-0900

Platelets and Blood Cells

Schattauer GmbH

Randomised, double-blind trial on the value of tapered discontinuation of clopidogrel maintenance therapy after drug-eluting stent implantation

Intracoronary Stenting and Antithrombotic Regimen: CAUTION in Discontinuing Clopidogrel Therapy – ISAR-CAUTION^[*]

K. Anette Fiedler

¹Deutsches Herzzentrum, Technische Universität, Munich, Germany

,

Julinda Mehilli

²Klinikum der LMU, Medizinische Klinik und Poliklinik I, Munich, Germany

⁴DZHK (German Centre for Cardiovascular Research), Partner sites Munich Heart Alliance, Munich, Germany

,

Sebastian Kufner

¹Deutsches Herzzentrum, Technische Universität, Munich, Germany

,

Anna Schlichting

¹Deutsches Herzzentrum, Technische Universität, Munich, Germany

,

Tareq Ibrahim

³Klinikum rechts der Isar, Technische Universität, 1. Medizinische Klinik und Poliklinik, Munich, Germany

,

Dirk Sibbing

²Klinikum der LMU, Medizinische Klinik und Poliklinik I, Munich, Germany

⁴DZHK (German Centre for Cardiovascular Research), Partner sites Munich Heart Alliance, Munich, Germany

,

Ilka Ott

¹Deutsches Herzzentrum, Technische Universität, Munich, Germany

,

Heribert Schunkert

¹Deutsches Herzzentrum, Technische Universität, Munich, Germany

⁴DZHK (German Centre for Cardiovascular Research), Partner sites Munich Heart Alliance, Munich, Germany

,

Karl-Ludwig Laugwitz

³Klinikum rechts der Isar, Technische Universität, 1. Medizinische Klinik und Poliklinik, Munich, Germany

⁴DZHK (German Centre for Cardiovascular Research), Partner sites Munich Heart Alliance, Munich, Germany

,

Adnan Kastrati

¹Deutsches Herzzentrum, Technische Universität, Munich, Germany

⁴DZHK (German Centre for Cardiovascular Research), Partner sites Munich Heart Alliance, Munich, Germany

,

Stefanie Schulz

¹Deutsches Herzzentrum, Technische Universität, Munich, Germany

› Author Affiliations

Abstract

Summary

There is little evidence on the optimal mode of clopidogrel discontinuation. Epidemiological studies observed clustering of thrombotic events after cessation of chronic clopidogrel therapy. The underlying mechanism has been ascribed to transient platelet hyper-reactivity. Gradual tapering of clopidogrel may have the potential to attenuate this phenomenon. The objective of the present study was to assess whether in patients with drug-eluting stents (DES) gradual discontinuation of clopidogrel maintenance therapy is superior to conventional, abrupt discontinuation. Patients with planned discontinuation of chronic clopidogrel therapy after DES implantation were randomised in a double-blinded fashion to either gradual discontinuation (according to a tapering schema over four weeks) or abrupt discontinuation (after continued clopidogrel therapy for additional four weeks). The primary endpoint was the composite of cardiac death, myocardial infarction, stroke, stent thrombosis, major bleeding or rehospitalisation due to an acute coronary syndrome at 90 days. Enrollment of 3,000 patients was planned. The study was stopped prematurely due to slow recruitment after enrollment of 782 patients. At 90 days, nine of 392 patients (2.3%) with tapered cessation reached the primary endpoint compared to five of 390 patients (1.3%) with abrupt cessation (p=0.284). The composite of death or myocardial infarction occurred in three patients with tapered and three patients with abrupt discontinuation (p=0.764). In conclusion, tapered discontinuation of chronic clopidogrel therapy is not superior to abrupt discontinuation regarding the primary endpoint in this study. However, the results must be interpreted in view of the premature termination of the trial and low event rates.

Keywords

Clopidogrel - tapering - rebound - drug-eluting stent

Full Text

References

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