Prevalence And Natural History Of Aspirin Responsiveness Measured By Whole Blood Aggregometry In Patient With Unstable Angina Pectoris

Background and objectivesDespite the efficacy of low-dose aspirin in preventing ischemic complications of atherothrombotic disease, aspirin does not benefit all patients equally, since a substantial proportion of patients receiving aspirin still suffer thrombo-embolic vascular events. However, there is currently no standardized approach to assess aspirin effect, and previous studies have estimated that 5.5% ~ 45% of the population are aspirin-resistant by means of various assays. Also, the profile and nature history of aspirin resistance have not yet been fully elucidated.The purposes of this study were: (1)to identify the preferred agent, and next with it, to evaluate aspirin responsiveness in patients with unstable angina pectoris (UAP) by whole blood aggregometry (WBA); (2) to examine whether aspirin resistance measured by this assay among UAP patients is associated with a higher risk of major adverse cardiovascular events (MACEs) in the follow-up.Materials and methodsFirstly, to determine the preferred agent, sixty patients with documented coronary artery disease were assigned to receive aspirin alone (ASA 100 mg/d) (n = 30) or aspirin-plus-clopidogrel (ASA 100 mg/d + C 75 mg/d) (n = 30). Platelet aggregation assessment by the use of WBA with collagen or ADP was performed in these patients and 30 normal volunteers. Next, we measured platelet aggregation by determining impedance values in 70 normal volunteers and 104 UAP patients on aspirin (100 mg/d≥7 days) with the preferred agent. We calculated a cutoff value based on data from normal volunteers to define aspirin responsiveness in cases. Aliquots from all samples were incubated with 0.1 mmol/L aspirin and measured again for aspirin-resistant classification.Secondly, the same cohort was followed up for a mean of six months. The primary end points were composites of cardiovascular death, nonfatal myocardial infarction (MI), revascularization, stroke/transient ischemic attack, and worsening UAP requiring re-hospitalization.ResultsWhen compared with the control group, therapy with ASA or ASA + C resulted in significant inhibition of collagen-induced platelet aggregation (P < 0.001 for each), but there was no statistically significant difference in the results between the ASA and ASA + C groups. When platelet aggregation was induced by ADP, the combined therapy with aspirin and clopidogrel decreased platelet aggregation significantly when compared with aspirin alone (P < 0.001), and no significant difference in the results between the ASA and normal groups was observed. And thus, collagen was chosen to study the antiplatelet effect of aspirin. Next, with 1μg/mL collagen and 2μg/mL collagen, aspirin resistance was observed in 38 patients (36.5%) and 51 patients (49.0%) among 104 cases, respectively. Collagen at low concentration (1μg/mL) was suggested as a preferred agent for detecting aspirin inhibitory effect according to coefficient of sensitivity. After incubation, only 3 among 38 aspirin-resistant patients showed normal platelet aggregation, and were classified into pharmacodynamic type.In the course of six months, only 1 patient in the aspirin-sensitive group failed to continue the follow-up procedure, and MACEs occurred in 24 patients (23.3%). Patients with aspirin resistance were not suggested having a higher risk of clinical events compared to those who were aspirin-sensitive (28.9% vs 20.0%, P > 0.05). Cox regression analysis showed that aspirin resistance seemed to have no correlation with six-month clinical outcome (HR, 1.559; 95% CI, 0.698-3.483; P > 0.05).ConclusionsCollagen at low concentration (1μg/mL) may prove useful to study aspirin effect by WBA. In the presence of 1μg/mL collagen, the prevalence of aspirin resistance is about 36.5% in UAP patients, and most of aspirin"resistance"is just due to pharmacokinetic issues. However, in the six-month follow-up, aspirin resistance defined by WBA is not associated with an increased risk of MACEs in UAP patients. The clinical significance of aspirin responsiveness detected by platelet function tests requires further evaluation in larger longitudinal studies.