title: On-clopidogrel platelet reactivity as predictor for long-term clinical outcome in patients after planned discontinuation of clopidogrel.
abstract: It is unknown whether the known association of high on-treatment platelet reactivity (HTPR) with worse clinical outcome in patients on clopidogrel following coronary stent implantation persists after planned discontinuation of clopidogrel. This study investigated the association of HTPR with major ischaemic events after planned discontinuation of clopidogrel. Consecutive patients undergoing elective coronary stent implantation after loading with clopidogrel 600 mg were followed for up to seven years (n=765). Platelet reactivity was tested on day 1 after coronary intervention. Clopidogrel was continued for six months after implantation of drug-eluting stents and for one month if only bare-metal stents were used. The combined primary endpoint was death of any cause or non-fatal myocardial infarction (MACE). HTPR was found in 217 of 765 patients (28 %). During a median follow-up of 5.7 years, the primary endpoint occurred in 145 subjects after planned discontinuation of clopidogrel. Patients with HTPR showed a higher incidence of MACE after discontinuation of clopidogrel. There was a significant interaction of HTPR and time following discontinuation of clopidogrel beyond one year (p for interaction 0.08). Landmark analyses confirmed that the association of HTPR and MACE was only significant within the first year (HR: 2.93, 95 %-CI 1.13-7.60, p=0.03), but not beyond the first year following discontinuation of clopidogrel (HR: 1.19, 95 %-CI 0.82-1.72, p=0.37). In conclusion, patients with HTPR persist to be at high risk for death or myocardial infarction even following planned discontinuation of clopidogrel. However, this association was only significant for the first year following discontinuation of clopidogrel.
authors.affiliation: Willibald, Hochholzer, MD, University Heart Center Freiburg · Bad Krozingen, Department of Cardiology and Angiology II, Suedring 15, 79189 Bad Krozingen, Germany, Tel.: +49 7633 4285, Fax: +49 7633 402 2489, E-mail: willibald.hochholzer@universitaets-herzzentrum.de.
authors.forename: Timo
authors.initials: T
authors.lastname: Bömicke
authors.forename: Christian M
authors.initials: CM
authors.lastname: Valina
authors.forename: Christian
authors.initials: C
authors.lastname: Stratz
authors.forename: Michael
authors.initials: M
authors.lastname: Amann
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Neumann
authors.forename: Willibald
authors.initials: W
authors.lastname: Hochholzer
mesh_terms: D000368:Aged; D000077144:Clopidogrel; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000401:mortality / Q000628:therapy*; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D005858:Germany; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000295:instrumentation / Q000401:mortality; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010979:Platelet Function Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: Antiplatelet therapy; discontinuation; outcome; platelet function