Clopidogrel (Plavix) is used to prevent the formation of a thrombus (clot) in vulnerable patients. However, a significant proportion of patients who receive clopidogrel remain at risk for subsequent death, myocardial infarction, stent thrombosis, and stroke because of insufficient clopidogrel-induced platelet inhibition.

Using customized relational databases with the capacity to rapidly mine data and identify previously-unknown relationships, McCormack Pharma reveals an amazing insight into why some people fail to adequately respond to the life-saving effects of the anti-platelet drug clopidogrel. This new report identifies free fatty acids as the final arbiter in determining the magnitude of clopidogrel resistance.

Unless clopidogrel’s blockade of the P2Y12 receptor pool on the platelet surface is 100% then above a threshold free fatty acids will augment signalling by the remaining few functional ADP-occupied receptors and drive the platelet toward aggregation. Consequently, in patients with CYP2C19 loss-of-function polymorphisms who coincidentally also have raised levels of free fatty acids, then the effects of an increased loading dose of clopidogrel will be non-linearly compromised when there is less than total blockade of the P2Y12 receptor pool. In these patients the answer is to lower the level of free fatty acids.

Maximising the efficacy of clopidogrel can only be achieved by “switching off” the endogenous and dominant modulation by elevated levels of free fatty acids, especially in patients who carry CYP2C19 loss-of-function polymorphisms.

“In these patients attempts to maximize clopidogrel efficacy through just stepping up the dose may be likened to a futile effort to slow a speeding vehicle through use of the brakes while the throttle remains wide open; attenuating levels of abnormally-raised levels of free fatty acids appears to offer a straightforward solution” …comments Dr Keith McCormack, founder and Head of Research at McCormack Pharma.