High Rate of Aspirin Resistance among Patients Undergoing Per-Cutaneous Intervention for Unstable Angina Is Associated with Clinical Outcome.
Authors: Abdelrahman Nader , Brill Alexander , Touretsky Natalia , Mosseri Elinor , Mosseri Moris , Varon David 
Published: October 2019

Abstract
The response to anti-platelet therapy may affect clinical outcome in patients with ischemic heart disease. We prospectively investigated the response to aspirin and clopidogrel in unstable angina patients undergoing per-cutaneous intervention (PCI). Platelet function was analyzed using an aggregometer and the Cone and Platelet Analyzer (CPA) tests. In the CPA test, preincubation of blood samples with sub-optimal concentrations of arachidonic acid (AA) or ADP results in decreased platelet deposition under flow. The test was used to evaluate platelet responsiveness to aspirin and clopidogrel. Preliminary studies have demonstrated that this method is useful in detecting the response to aspirin in healthy volunteers. All patients (87) received aspirin treatment prior to hospitalization. On admission, the response to aspirin as tested by the CPA method was unexpectedly low, surface coverage (SC) with AA 2.2±0.2% (mean ± SE), with ADP 1.7±0.2%, reflecting a response rate of 26.9%. Comparable results were obtained using aggregometry, with 33.9±2.6% maximal aggregation in response to AA and 60.7±3.1% maximal aggregation in response to ADP, reflecting a response rate to aspirin of 33.3%. On the second day, after receiving 300 mg clopidogrel, the CPA assay with ADP revealed a significant response to the drug (SC 4.1±0.4%). Moreover, testing with AA on the second day demonstrated an increased response rate to aspirin (SC 4.6±0.3%), suggesting a cooperative effect of the two drugs. These results reflect response rate to aspirin of 75.4% on the second day. Aggregometry testing on the second day revealed an increased response rate up to 84.0% (maximal aggregation with AA 18.3±2.2% and with ADP 23.3±2.2%). A sub-group of 50 patients examined 6 months after the hospitalization demonstrated that the high response rate to aspirin (90%, SC 6.1±0.6%) was preserved nevertheless clopidogrel treatment had been discontinued. At the same time, according to aggregometry with AA, only 68% response rate to aspirin was observed (25.5±3.8% maximal aggregation). The response to ADP in both assays returned to the control level (SC 2.2±0.2%; maximal aggregation 70.5±3.1%), reflecting the fact that all tested patients were off clopidogrel therapy at this point. A prospective clinical evaluation revealed that 7 out of 8 patients who required additional PCI (balloon or stent) during the first 6 months after discharge were unresponsive to aspirin on the day of hospitalization as judged by both methods. In contrast, these patients except one became responders to aspirin on day 2 and after 6 months, as tested by both methods. In conclusion: a) a low response rate to aspirin was observed in patients with unstable angina undergoing PCI; b) loading dose of 300 mg of clopidogrel significantly increased the response to aspirin accordnig to both methods; c) aspirin resistance on admission might predict future complications; d) the CPA test was found useful for monitoring the effects of both aspirin and clopidogrel, and e) clopidogrel therapy before PCI in unstable angina (at least for aspirin resistant patients), may improve clinical outcome.