Oral anticoagulation with coumarin derivatives and antiplatelet effects of clopidogrel.
OBJECTIVE
A relevant proportion of patients receiving aspirin and clopidogrel after percutaneous coronary intervention (PCI) also require oral anticoagulation with a coumarin derivative such as phenprocoumon. Both clopidogrel and phenprocoumon are metabolized by the hepatic cytochrome P450 system and a drug-drug interaction may exist at this level. The aim of this study was to investigate the impact of phenprocoumon on the antiplatelet effects of clopidogrel in patients with coronary artery disease.


RESULTS
Patients (n = 1223) eligible for this study were under dual maintenance antiplatelet treatment with aspirin and clopidogrel. Adenosine diphosphate-induced platelet aggregation (in AU*min) was measured with multiple electrode platelet aggregometry on a Multiplate analyzer (Dynabyte, Munich, Germany). From the entire study population, 124 (10.1%) patients were under concomitant phenprocoumon treatment at the time point of platelet function testing. Platelet aggregation (median [interquartile range]) was significantly higher in patients with (n = 124) concomitant phenprocoumon treatment compared with patients without (n = 1099) phenprocoumon treatment (308 [190-493] AU*min vs. 224 [145-390] AU*min; P = 0.0001, adjusted P = 0.002).


CONCLUSIONS
Phenprocoumon significantly attenuates the antiplatelet effects of clopidogrel. The impact of this interaction on the risk of thrombotic and bleeding events after PCI requires further investigations.
Deutsches Herzzentrum and 1. Medizinische Klinik rechts der Isar, Technische Universität München, Lazarettstrasse, Munich, Germany. dirk@sibbing.net
Dirk
D
Sibbing
Nicolas
N
von Beckerath
Tanja
T
Morath
Julia
J
Stegherr
Julinda
J
Mehilli
Nikolaus
N
Sarafoff
Siegmund
S
Braun
Stefanie
S
Schulz
Albert
A
Schömig
Adnan
A
Kastrati
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy*; D003430:Cross-Sectional Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010644:Phenprocoumon / Q000008:administration & dosage / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000627:therapeutic use
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine; D010644:Phenprocoumon; D001241:Aspirin