Platelet function tests are not equally effective in measuring aspirin's antiplatelet effect and correlate poorly amongst themselves. The clinical usefulness of the different assays to classify correctly patients as aspirin resistant remains undetermined.

Current available data show that about 4% to 30% of patients treated with conventional doses of clopidogrel do not display adequate antiplatelet response. Clopidogrel resistance is a widely used term that remains to be clearly defined. So far, it has been used to reflect failure of clopidogrel to achieve its antiaggregatory effect. The interpatient variability in clopidogrel response is multifactorial. It can be due to extrinsic or intrinsic mechanisms. Among extrinsic mechanisms are the possibility of clopidogrel underdosing in patients undergoing stenting or with acute coronary syndrome, and drug-drug interactions involving CYP3A4. Intrinsic mechanisms include genetic polymorphisms of the P2Y(12) receptor and of the CYP3As, accrued release of adenosine diphosphate, or up-regulation of other platelet activation pathways. Presently, there is no definite demonstration of an association between low responsiveness to clopidogrel and thrombotic events. The optimal level of clopidogrel-induced platelet inhibition, which will correlate quantitatively with clopidogrel's ability to prevent atherothrombotic events is still lacking. Furthermore, because there is no single and validated platelet function assay to measure clopidogrel's antiplatelet effect, it is not justified to routinely look for clopidogrel resistance in the clinical setting. This review discusses currently available evidence surrounding the variability in the antiplatelet response to clopidogrel.

The assessment of platelet function inhibition by clopidogrel is highly test-specific. Decision to increase clopidogrel dosage may vary on the basis of the assay used, thus highlighting the need for unambiguous guidelines with respect to assay selection, as platelet function assays are not interchangeable. At present, platelet function testing evaluating clopidogrel efficacy cannot be recommended in routine clinical practice.

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Canadian patients with cardiovascular disease commonly report the use of herbal products and vitamins. Allied health professionals need to be aware of the widespread use of these products and their potential for adverse reactions and drug interactions.

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Aspirin resistance is often defined as failure to demonstrate an inhibitory effect of aspirin on standard platelet function assays. Although many studies have been published on this phenomenon, the performance of individual assays to detect actual aspirin effects is poorly defined. The aim of this study is to define the sensitivity and potential limitations of five different assays of platelet function on detecting aspirin effects. A prospective cohort of 45 healthy volunteers consented to taking 80 mg of non-coated aspirin for 8–10 days. Participants were selected if they were non-smokers, did not present any significant medical condition and were excluded if they had ingested any potential drug / supplement known to effect platelet function in the past 10 days or were found to have abnormal blood counts. Samples were collected immediately prior to the first aspirin dose and repeated after 8 to 10 days of aspirin therapy. The study population consisted of 16 males and 29 females, 19 to 59 years of age without acquired cardiovascular risk factors and a mean BMI of 24,1 (range: 18,8–32,5). Study drug intake was carefully monitored by patient questionnaire and unused pill count at the second study visit. Partial non compliance was identified in 4 participants (1–2 missed doses) although no missed doses occurred in the last 3 days of the study. Mean delay between the last aspirin dose and the post study sample was 221 minutes (range 60 to 720 min, 5 patients with delays over 6 hours). Test characteristics and performances in detecting aspirin intake in our population are resumed in the table below. Conclusion: Although aspirin clearly has an effect in all the assays tested, the broad distribution of values with LTA-ADP, platelet count drop, TEG-MA(AA) and urinary dTxB2 does not allow accurate discrimination of aspirin effects in healthy individuals. Considering their adequate distinction between subjects on and off aspirin, we suggest that LTA-AA and the VerifyNow assay should be preferred in studies evaluating aspirin effect and potential resistance to this drug. Findings such as ours should serve to better define the limitations of laboratory studies of platelet function for the assessment of aspirin effects. Table 1. Test performance characteristics LTA-AA 1,6 mM (%) LTA-ADP 10 umol (%) VerifyNow (ARU) Platelet count drop (%) TEG-MAAA(%) dTxB2 (pg/ml) * 95% confidence intervals; **paired t-test, ***as suggested by Gum et al, ¤as suggested by manufacturer, 2best fit on ROC curve Prior to ASA 61,2 (33,9;88,4)* 74,2 (35,1;113,3) 634,5 (564,8;704,3) 74,9 (35,3;114,4) 100,6 (27,2;174) 240,8 (0;821) After ASA 2,4 (0;7,9) 40,4 (0;85,8) 407,9 (355,7;460,1) 41,5 (8,8;74,3) 53,2 (−44,4;150,8) 115 (0;407,9) p value** <10e-29 <10e-13 <10e-32 <10e-10 <10e-7 <10e-6 Proposed cut-off values < 20%*** < 70%*** <550 ARU¤ <55%2 < 90%2 < 602 Sensitivity 100 % 84,4 % 100 % 82,2 % 82,9 % 62,2% Specificity 95,6 % 77,8 % 95,6 % 86,7 % 75,8 % 82,2%