Antiplatelet effect of clopidogrel is reduced in patients treated with therapeutic hypothermia after cardiac arrest.
BACKGROUND
The platelet inhibitor clopidogrel is administered to patients treated with therapeutic hypothermia following cardiac arrest due to acute coronary syndromes. Interactions with proton pump inhibitors and genetics are factors with a known potential to attenuate the platelet inhibition of clopidogrel. In patients treated with therapeutic hypothermia, reduced gastrointestinal function and hypothermia may also reduce the effect of clopidogrel. To investigate the net platelet inhibition of clopidogrel, we have measured the platelet reactivity index in patients treated with therapeutic hypothermia.


RESULTS
Twenty-five Caucasian patients treated with clopidogrel and therapeutic hypothermia were prospectively included. Therapeutic hypothermia was defined as 33-34°C and delivered for 24h. Clopidogrel loading doses (300-600 mg) were administered enterally the day of admission and followed by 75 mg daily. Blood samples were collected on day 1 (n=25) and day 3 (n=16). The samples were analysed for inhibition by clopidogrel with a vasodilator stimulated phosphoprotein phosphorylation kit. On day 1 and day 3, platelet reactivity index was 0.77±0.09 and 0.57±0.16, respectively. The number of patients with a satisfactory antiplatelet effect (defined as platelet reactivity index <0.5) were 0 (0%) and 5 (31%), respectively.


CONCLUSIONS
In patients treated with therapeutic hypothermia after cardiac arrest, the effect of clopidogrel on platelets was virtually nonexistent on day 1 after administration, with some improvement on day 3.
Bjelland
Thor Wilhelm
TW
Department of Circulation and Medical Imaging, Medical Faculty, Norwegian University of Science and Technology, 7006 Trondheim, Norway. thorwilh@stud.ntnu.no
Hjertner
Øyvind
Ø
Klepstad
Pål
P
Kaisen
Kjell
K
Dale
Ola
O
Haugen
Bjørn Olav
BO
D054058:Acute Coronary Syndrome / Q000150:complications; D000077144:Clopidogrel; D005260:Female; D006323:Heart Arrest / Q000628:therapy*; D006801:Humans; D007036:Hypothermia, Induced; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011446:Prospective Studies; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine