REsistance to Aspirin and Clopidogrel in acuTe Myocardial Infarction (REACT-MI)

University Hospital Ostrava

Status and phase

Completed

Phase 4

Conditions

Acute Myocardial Infarction

Treatments

Drug: Aspirin 200mg qd, Clopidogrel 2x75mg qd

Study type

Interventional

Funder types

Other

Identifiers

NCT01381185

FNO-KVO-1

plasek680 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to compare 3 point-of-care methods for monitoring antiplatelet therapy to golden standard (Light transmittance aggregometry-LTA) in high risk population of acute myocardial infarction patients. If two methods (PFA-100, VerifyNOW,Multiplate or LTA) will indicate insufficient antiplatelet blockade/high residual reactivity for aspirin, clopidogrel or both, the dose of aspirin will be increased to 200mg qd and the dose of clopidogrel will be increased to 2x75mg qd.In addition genotyping of CYP2C19 (6 alleles) will be performed.

Full description

Dual antiplatelet therapy is the cornerstone of treatment of coronary heart disease after coronary stent implantation. The interindividual response to this therapy is not uniform, however. There are subgroups of patients, where no anticipated antiplatelet effect to either aspirin, clopidogrel or both is reached. The term of aspirin/clopidogrel resistance has been introduced few years ago, most recently it was substituted by more suitable term - high on-treatment residual platelet reactivity (HPR). Although there are many assays to monitor antiplatelet therapy, uncertainty still remains about the correlation of HPR with ischemic vascular events (in-stent thrombosis, myocardial infarction, etc.). Thus platelet aggregation testing is considered to be the most promising method to indicate inappropriate/low response to aspirin/clopidogrel, however the best suited method is not established yet. Up-to date light transmittance aggregometry is widely accepted as golden standard, nonetheless labour intensive and difficult to standardize. On the other hand many point-of-care aggregation testing methods like PFA-100, VerifyNOW, Multiplate etc. have been introduced, their role in clinical practice is uncertain, however. The biggest challenge of today is to determine platelet function assay, which could reliably indicate future ischemic vascular events;moreover it could be potentially used to tailor antiplatelet therapy and precede these events. It was demonstrated, that gene polymorphism - CYP2C19*2 and CYP2C9*3 loss of function is conjugated with an increased occurrence of stent thrombosis. Within the project we also plan to examine 4 alleles which have not been examined in detail before.

Enrollment

154 patients

Sex

All

Ages

21 to 90 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

acute myocardial infarction (verified by troponin I elevation and ST-segment deviation ≥0.1mV in ≥2 contiguous ECG leads persisting for at least 20 minutes and angiographical proof of coronary stenosis )
preceding antiplatelet medication with aspirin100mg qd/5 and more days before PCI
pre-treatment with 600mg Clopidogrel loading dose
preferably patients with drug eluting stent implantation
signed informed consent

Exclusion criteria

stable/unstable angina pectoris
active malignancy
contraindication to antiplatelet therapy
increased risk of bleeding (trauma, surgery or non-ischemic stroke in last month)
effective anticoagulation therapy:LMWH, Pradaxa, Xarelto, Warfarin
known thrombophile disorder
SIRS
renal insufficiency (eGFR under 15ml/min)
severe anemia (<80 g/l)
polyglobulia (>160 g/l)
pregnancy
Hematocrit <0.25 > 0.55