Comparison of Different Laboratory Tests to Identify “Aspirin Resistance” and Risk of Vascular Events among Ischaemic Stroke Patients: A Double-Blind Study

Abstract

“Aspirin resistance” (AR) is associated with increased risk of vascular events. We aimed to compare different platelet function tests used in identifying AR and assess their implications on clinical outcome. We performed platelet aggregation studies on non-cardioembolic ischaemic stroke patients taking aspirin 100 mg/day and 30 non-stroke controls. Data were collected on demographics, vascular risk factors, and concomitant medications. Cut-offs for AR were (1) light transmission aggregometry (LTA) of ≥20% using arachidonic acid (AA), ≥70% using ADP, or ≥60% using collagen; and (2) VerifyNow® assay ≥ 550 ARU. Telephone follow-ups were conducted by study staff blinded to AR status to ascertain the occurrence of vascular outcomes (stroke, myocardial infarction, amputation, death). A total of 113 patients were recruited, mean age 65 ± 8 years, 47% women, 45 ± 15 days from index stroke. 50 (44.3%, 95% CI 34.9–53.9) had AR on at least 1 test. Frequency of AR varied from 0% to 39% depending on method used and first vs. recurrent stroke. There were strong correlations between LTA AA, VerifyNow® and Multiplate® ASPItest (r = 0.7457–0.8893), but fair to poor correlation between LTA collagen and Multiplate® COLtest (r = 0.5887) and between LTA ADP and Multiplate® ADPtest (r = 0.0899). Of 103 patients with a mean follow up of 801 ± 249 days, 10 (9.7%) had vascular outcomes, of which six had AR by LTA-ADP. AR by LTA-ADP is associated with increased risk of vascular outcome (p = 0.034). Identification of AR is not consistent across different platelet function tests. LTA of ≥70% using 10 µM ADP in post-stroke patients taking aspirin is associated with increased risk of vascular outcome.

Aspirin Resistance in Vascular Disease: A Review Highlighting the Critical Need for Improved Point-of-Care Testing and Personalized Therapy

“…Numerous studies have established ≥20% aggregation in response to arachidonic acid by LTA as a diagnostic cut-off for aspirin resistance [ 61 , 62 , 63 , 64 , 65 , 66 , 67 ]. Previous studies have also established a link between patients with ≥20% aggregation and significant increase in the risk of cardiovascular and thrombotic events [ 38 , 54 ].…”

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“…However, many people may not respond to aspirin despite its widespread usage for a wide variety of conditions. These people are also known as non-aspirin responders [11]. This condition, also known as aspirin resistance, has received a lot of attention from researchers.…”

Genetic Association Study and Machine Learning to Investigate Differences in Platelet Reactivity in Patients with Acute Ischemic Stroke Treated with Aspirin

“…Among the assays that determine platelet function, light transmission aggregometry (LTA) is considered as the gold standard in platelet function testing [ 11 ]. Automated (point-of-care) assays such as VerifyNow ® , PFA-100 ® , Multiplate ® , Plateletworks ® and others are widely used for monitoring platelet response to antiplatelet agents including aspirin [ 6 , 12 , 13 ]. HTPR was shown to increase the risk of recurrent vascular events and long-term clinical outcomes for patients with cerebrovascular pathology [ 14 , 15 , 16 , 17 ].…”

“…HTPR was shown to increase the risk of recurrent vascular events and long-term clinical outcomes for patients with cerebrovascular pathology [ 14 , 15 , 16 , 17 ]. Nevertheless, platelet function tests differ in their ability to predict the risk of cardiovascular outcomes [ 12 ].…”