Most studies indicated that low on-treatment platelet reactivity ( LTPR ) , as measured by several platelet function tests , and the carriage of CYP2C19 * 17 allele were independent risk factors for bleeding .
A bleeding score also proved to be helpful in identifying patients at risk .
Several patient characteristics were also identified as independent predictors of bleeding , such as older age , female sex and renal failure .
Patients with coronary artery disease are usually treated with dual antiplatelet therapy ( DAPT ) after percutaneous coronary intervention .
Patients on DAPT are at risk of both ischaemic and bleeding events .
Although side-lined for a long time , real-life studies have shown that both the incidence and the associated morbidity and mortality of out-of-hospital bleeding are high .
This indicates that prevention of ( post-interventional ) bleeding is as important as prevention of ischaemia .
For this purpose it is crucial to reliably identify patients with a high bleeding risk .
In order to postulate an algorithm , which could help identifying these patients , we performed a systematic review to determine the value of previously proposed prognostic modalities for bleeding .
Paraoxonase-1 is a major determinant of clopidogrel efficacy
Clinical efficacy of the antiplatelet drug clopidogrel is hampered by its variable biotransformation into the active metabolite . The variability in the clinical response to clopidogrel treatment has been attributed to genetic factors , but the specific genes and mechanisms underlying clopidogrel bioactivation remain unclear . Using in vitro metabolomic profiling techniques , we identified paraoxonase-1 ( PON1 ) as the crucial enzyme for clopidogrel bioactivation , with its common Q192R polymorphism determining the rate of active metabolite formation . We tested the clinical relevance of the PON1 Q192R genotype in a population of individuals with coronary artery disease who underwent stent implantation and received clopidogrel therapy .  PON1 QQ192 homozygous individuals showed a considerably higher risk than RR192 homozygous individuals of stent thrombosis , lower PON1 plasma activity , lower plasma concentrations of active metabolite and lower platelet inhibition . Thus , we identified PON1 as a key factor for the bioactivation and clinical activity of clopidogrel . These findings have therapeutic implication s and may be exploited to prospect ively assess the clinical efficacy of clopidogrel
Most studies indicated that low on-treatment platelet reactivity ( LTPR ) , as measured by several platelet function tests , and the carriage of CYP2C19 * 17 allele were independent risk factors for bleeding .
A bleeding score also proved to be helpful in identifying patients at risk .
Several patient characteristics were also identified as independent predictors of bleeding , such as older age , female sex and renal failure .
Patients with coronary artery disease are usually treated with dual antiplatelet therapy ( DAPT ) after percutaneous coronary intervention .
Patients on DAPT are at risk of both ischaemic and bleeding events .
Although side-lined for a long time , real-life studies have shown that both the incidence and the associated morbidity and mortality of out-of-hospital bleeding are high .
This indicates that prevention of ( post-interventional ) bleeding is as important as prevention of ischaemia .
For this purpose it is crucial to reliably identify patients with a high bleeding risk .
In order to postulate an algorithm , which could help identifying these patients , we performed a systematic review to determine the value of previously proposed prognostic modalities for bleeding .