Optimizing P2Y12 receptor inhibition in patients with acute coronary syndrome on the basis of platelet function testing: impact of prasugrel and high-dose clopidogrel.
OBJECTIVE
This study sought to evaluate the impact of treatment with prasugrel and high-dose clopidogrel on the basis of platelet function testing in patients with acute coronary syndrome (ACS) who are undergoing percutaneous coronary intervention (PCI).


BACKGROUND
The clinical impact of treatment with prasugrel in patients with ACS who have high platelet reactivity (HPR) is unknown.


METHODS
Patients with ACS who were pre-treated with clopidogrel and undergoing successful PCI were enrolled in a single-center, prospective registry. Platelet function was measured 12 to 36 h after PCI with the Multiplate device (Roche Diagnostics GmbH, Mannheim, Germany). Patients with HPR (>46 U) were switched to prasugrel or treated with high-dose clopidogrel, and those without HPR continued treatment with 75 mg of clopidogrel.


RESULTS
A total of 741 consecutive patients were enrolled in the study between September 2011 and August 2012, and 219 of these patients (29.5%) had HPR. Although platelet reactivity decreased after treatment adjustments in those with HPR, prasugrel provided significantly more potent platelet inhibition compared with high-dose clopidogrel (p < 0.0001). Compared with patients without HPR, the risk of all-cause death, myocardial infarction, stent thrombosis, or stroke at 1 year was significantly higher in the high-dose clopidogrel group (hazard ratio [HR]: 2.27; 95% confidence interval [CI]: 1.45 to 3.55; p < 0.0001), and patients who were switched to prasugrel had similar outcomes (HR: 0.90; 95% CI: 0.44 to 1.81; p = 0.76). Bleeding Academic Research Consortium (BARC) type 3/5 bleeding was also more frequent in patients treated with high-dose clopidogrel (HR: 2.09; 95% CI: 1.05 to 4.17; p = 0.04) than in patients switched to prasugrel (HR: 0.45; 95% CI: 0.11 to 1.91; p = 0.28). In a multivariate model, HPR with high-dose clopidogrel, but not with prasugrel, was an independent predictor of the composite ischemic endpoint (HR: 1.90; 95% CI: 1.17 to 3.08; p = 0.01).


CONCLUSIONS
Switching patients with ACS who have HPR to treatment with prasugrel reduces thrombotic and bleeding events to a level similar to that of those without HPR; however, there is a higher risk of both thrombotic and bleeding complications with high-dose clopidogrel.
Department of Cardiology, Heart Center Balatonfüred, Balatonfüred, Hungary. Electronic address: daniel_aradi@yahoo.com.
Dániel
D
Aradi
Heart Institute, University of Pécs, Pécs, Hungary.
Adrienn
A
Tornyos
Heart Institute, University of Pécs, Pécs, Hungary.
Tünde
T
Pintér
Heart Institute, University of Pécs, Pécs, Hungary.
András
A
Vorobcsuk
Heart Institute, University of Pécs, Pécs, Hungary.
Attila
A
Kónyi
Department of Cardiology, Heart Center Balatonfüred, Balatonfüred, Hungary.
József
J
Faluközy
Department of Cardiology, Heart Center Balatonfüred, Balatonfüred, Hungary.
Gábor
G
Veress
Heart Institute, University of Pécs, Pécs, Hungary.
Balázs
B
Magyari
Heart Institute, University of Pécs, Pécs, Hungary.
Iván G
IG
Horváth
Heart Institute, University of Pécs, Pécs, Hungary.
András
A
Komócsi
D054058:Acute Coronary Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality* / Q000628:therapy; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000379:methods; D002423:Cause of Death; D000077144:Clopidogrel; D003131:Combined Modality Therapy; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage*; D012042:Registries; D018570:Risk Assessment; D012720:Severity of Illness Index; D015607:Stents; D020521:Stroke / Q000517:prevention & control; D015996:Survival Rate; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects; D013927:Thrombosis / Q000517:prevention & control; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D010879:Piperazines; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine
PCI; bleeding; high platelet reactivity; high-dose clopidogrel; mortality; platelet function testing; prasugrel; stent thrombosis