Platelet response to aspirin and clopidogrel in patients with peripheral atherosclerosis

Abstract

Aspirin and clopidogrel are important drugs in the secondary prevention of ischemic events. A considerable individual variation in platelet response to these drugs has, however, been reported, and high residual platelet reactivity despite treatment may be an independent risk factor for ischemic events. Most studies have been undertaken in patients with coronary heart disease, but patients with peripheral artery disease (PAD) may exhibit greater residual platelet reactivity, possibly because of platelet activation by a larger area of diseased endothelium. It is yet unsettled which method that best measures platelet reactivity and an eventual lack of response to aspirin. Several instruments are promoted to measure platelet response and low-response to platelet inhibitors, but it is questionable if they measure this in comparable ways. We studied the comparability of three tests of platelet reactivity for the assessment of low-response to aspirin and clopidogrel in patients with PAD. In 263 patients, platelet function was assessed twice, 3 months apart, by the Platelet Function Analyzer-100 (PFA), light transmission aggregometry (LTA), and whole blood impedance aggregometry (IA). In a subgroup of 43 patients, we studied the effect of a single dose of 600 mg clopidogrel on platelet function. Low-response to aspirin assessed by analyses targeting cyclooxygenase-1 activity (LTA, IA) was rare (≤ 8.1%). With the PFA, we found 17% with low response at both visits, and 60% who were consistently responsive, whereas 23% were categorized differently at the two visits. Low response to clopidogrel, occurred in 0-23%, depending on the method and the criteria used. A low-response to aspirin, defined by lack of COX-1 inhibition, is a rare phenomenon whereas high residual platelet reactivity as determined by PFA may be a rather frequent finding but is not consistent over time in all patients. A low-response to clopidogrel depends very much on the method and definition used.

Review of aspirin and clopidogrel resistance in peripheral arterial disease

“…The authors remarked on the comparability of this study to the "moderate to poor agreement between methods used" in previous studies and the importance of continued research in the area. 33 Another 2011 study analyzing 80 PAD patients for AR using three different methods including optical aggregometry using arachidonic acid (AA) and adenosine diphosphate (ADP) as well as PFA revealed persistent AR prevalence over 12 months of 5%, 27.5%, and 9.9%, respectively. There was a statistically significant albeit small agreement between AA optical aggregometry and PFA.…”

Comparison of Three Tests to Distinguish Platelet Reactivity in Patients with Renal Impairment during Dual Antiplatelet Therapy

“…Since a majority of the platelet studies are historically conducted during loading DAPT phase in the setting of acute coronary syndromes, the index data are of special interest. Lack of agreement among the platelet assays has been previously described during DAPT [4,5,6,7], but this evidence is still hard to reasonably explain or comprehend. We conducted the multivariable regression analyses, which confirmed the advantage of the VerifyNow test over 2 other technologies.…”

“…The most important design feature of the VerifyNow-P2Y12 assay is the usage of the combination of ADP and prostaglandin E1 (PGE1) to directly measure the effects of clopidogrel on the P2Y12 receptor. However, the diagnostic utility of different platelet tests in RI DAPT patients is unclear, since the issue of comparability of platelet function tests in quantifying platelet inhibition achieved by DAPT is constantly emerging without definite solutions [4,5,6,7]. In this study, we measured and compared residual platelet reactivity in RI patients undergoing chronic DAPT by 3 conventional assays in a large cohort of post-stenting Korean patients.…”