Dual antiplatelet drug resistance in patients with acute coronary syndrome.
OBJECTIVE
Antiplatelet therapy is a cornerstone in the management of the atherosclerotic vascular disease. Aspirin and clopidogrel are the two most commonly used antiplatelet drugs in its management. Recently, there has been a concern about the development of resistance to one or both antiplatelet agents with potentially devastating consequences. In this study we tried to assess the in vitro resistance to antiplatelet agents in patients presenting with acute coronary syndrome (ACS).


METHODS
144 patients presenting with ACS, who were not on any antiplatelet therapy prior to hospital admission were evaluated in this study. Baseline clinical data was obtained before giving the oral loading dose of aspirin and clopidogrel. Patients received a loading dose of 325 mg of aspirin and 300 mg of clopidogrel followed by a daily dose of 150 mg. of aspirin and 75 mg.of clopidogrel. After 7 days of dual antiplatelet therapy, platelet aggregation pattern was analyzed using optical aggregometer (chrono-log). Response to aspirin and clopidogrel was assessed by interaction with collagen (2microg/ml) and Adenosine diphosphate (ADP) (10micro/ml) respectively. The results were analyzed. Response to doubling the dose of antiplatelet agents was also observed in 6 aspirin resistant patients, 12 clopidogrel resistant patients and in 6 patients resistant to the effect of dual antiplatelet agents.


RESULTS
There were 22 patients (15.27%) who showed poor response to aspirin, 28 patients (19.44%) to clopidogrel (primary non-responder) and 18 patients (12.5%) showed a primary non-responsiveness to both the antiplatelet agents in the usual doses. After dose doubling, all 6 aspirin resistant patients showed adequate response but 4 out of 12 clopidogrel resistant patients showed inadequate response.


CONCLUSIONS
This pilot study brings out a disquieting picture of 12.5% patients suffering from ACS showing resistance to the antiplatelet effects of both aspirin and clopidogrel in the conventional dose. A long-term prospective randomized controlled trial is required to give an insight into this problem and its clinical consequences.
Guha
Santanu
S
Department of Cardiology, Medical College, Kolkata, India. guhas55@hotmail.com
Sardar
Partha
P
Guha
Pradipta
P
Roy
Sarita
S
Mookerjee
Soura
S
Chakrabarti
Prantar
P
Deb
P K
PK
Chaudhuri
Utpal
U
Deb
Suryyani
S
Karmakar
Rathindranath
R
Dasgupta
Anjan Kr
AK
Lahiri
Prabir
P
D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D001241:Aspirin / Q000008:administration & dosage*; D000077144:Clopidogrel; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011446:Prospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin