Poor response to clopidogrel: current and future options for its management.
Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndromes and/or undergoing percutaneous coronary interventions (PCI). Clopidogrel, a thienopyridine antiplatelet agent, has been used to prevent vascular complication in atherothrombotic patients, to prevent stent thrombosis in patients undergoing PCI, and in long term prevention of cardiovascular and cerebrovascular events. More than 40 million patients in the world receive clopidogrel but unfortunately about 20% of these are either non or poor responders. Several methods have been used to assess clopidogrel-induced antiplatelet effects. However, none of these tests have been fully standardized or fully agreed upon to measure clopidogrel responsiveness. Nevertheless, many studies using different techniques, platelet agonists and definitions, showed that patients with a poor response to clopidogrel have an increased risk of death, reinfarction and stent thrombosis. The mechanisms leading to poor responsiveness are not fully clarified and are likely multifactorial: genetic factors, accelerated platelet turnover, up-regulation of the P2Y(12) pathways, high baseline platelet reactivity, poor compliance, under-dosing and drug-drug interactions. The management of these patients is very difficult, but some evidence showed that a strategy of higher maintenance dose or switch to different thienopyridine (e.g. ticlopidine or prasugrel) or use of glycoprotein IIb/IIIa inhibitors during PCI may be helpful to overcome poor responsiveness and improve the long-term clinical outcome. This paper reviews the impact of clopidogrel poor responsiveness on clinical outcomes, the mechanisms leading to poor effect and the different assays to assess it. Finally, current and future options for its management is discussed.
Cardiovascular Institute, Azienda Ospedaliera Universitaria S Anna, Ferrara, Italy. cmpglc@unife.it
Gianluca
G
Campo
Luca
L
Fileti
Marco
M
Valgimigli
Matteo
M
Tebaldi
Elisa
E
Cangiano
Caterina
C
Cavazza
Jlenia
J
Marchesini
Roberto
R
Ferrari
D002318:Cardiovascular Diseases / Q000188:drug therapy; D000077144:Clopidogrel; D019468:Disease Management; D005544:Forecasting; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017211:Treatment Failure
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine