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 .
Effects of CYP2C19 genotype on outcomes of clopidogrel treatment.
BACKGROUND It has been suggested that clopidogrel may be less effective in reducing the rate of cardiovascular events among persons who are carriers of loss-of-function CYP2C19 alleles that are associated with reduced conversion of clopidogrel to its active metabolite . METHODS We genotyped patients from two large , r and omized trials that showed that clopidogrel , as compared with placebo , reduced the rate of cardiovascular events ( the primary efficacy outcome ) among patients with acute coronary syndromes and among patients with atrial fibrillation . Patients were genotyped for three single-nucleotide polymorphisms ( * 2 , * 3 , * 17 ) that define the major CYP2C19 alleles . RESULTS Among 5059 genotyped patients with acute coronary syndromes , clopidogrel as compared with placebo significantly reduced the rate of the primary efficacy outcome , irrespective of the genetically determined metabolizer phenotype ( P=0.12 for heterogeneity ) . The effect of clopidogrel in reducing the rate of the primary efficacy outcome was similar in patients who were heterozygous or homozygous for loss-of-function alleles and in those who were not carriers of the alleles ( rate among carriers , 8.0 % with clopidogrel vs. 11.6 % with placebo ; hazard ratio with clopidogrel , 0.69 ; 95 % confidence interval [ CI ] , 0.49 to 0.98 ; rate among noncarriers , 9.5 % vs. 13.0 % ; hazard ratio , 0.72 ; 95 % CI , 0.59 to 0.87 ) . In contrast , gain-of-function carriers derived more benefit from clopidogrel treatment as compared with placebo than did noncarriers ( rate of primary outcome among carriers , 7.7 % vs. 13.0 % ; hazard ratio , 0.55 ; 95 % CI , 0.42 to 0.73 ; rate among noncarriers , 10.0 % vs. 12.2 % ; hazard ratio , 0.85 ; 95 % CI , 0.68 to 1.05 ; P=0.02 for interaction ) . The effect of clopidogrel on bleeding did not vary according to genotypic subgroups . Among 1156 genotyped patients with atrial fibrillation , there was no evidence of an interaction with respect to either efficacy or bleeding between the study treatment and the metabolizer phenotype , loss-of-function carrier status , or gain-of-function carrier status . CONCLUSIONS Among patients with acute coronary syndromes or atrial fibrillation , the effect of clopidogrel as compared with placebo is consistent , irrespective of CYP2C19 loss-of-function carrier status . ( Funded by Sanofi-Aventis and Bristol-Myers Squibb ; Clinical Trials.gov number , NCT00249873 . )
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 .