Ticagrelor as an Alternative Antiplatelet Therapy in Cardiac Patients Non-Sensitive to Aspirin

Abstract

Background and Objectives: Aspirin (acetylsalicylic acid—ASA) is a first-line antiplatelet therapy provided to patients with coronary artery disease (CAD). However, it has been demonstrated that 20–30% of these patients are non-sensitive to their ASA therapy. ASA non-sensitivity is a phenomenon where low-dose ASA (81–325 mg) does not completely inhibit arachidonic-acid-induced platelet aggregation, putting patients at risk of adverse cardio-thrombotic events. Ticagrelor is a P2Y12 receptor inhibitor and alternative antiplatelet that has been approved to reduce the risk of stroke, myocardial infarction, and overall cardiovascular-related death. In this study, we aimed to identify ASA non-sensitive patients and evaluate if they would be sensitive to ticagrelor. Materials and Methods: For this pilot study, thirty-eight patients with CAD taking 81 mg ASA were recruited. Blood samples were collected from each patient and platelet rich plasma (PRP) from each sample was isolated. Light-transmission aggregometry (LTA) was used to determine baseline ASA sensitivity in each patient using 0.5 mg/mL arachidonic acid as a platelet agonist. Patients with ≥20% maximal platelet aggregation after activation were considered ASA non-sensitive. Fresh PRP samples from all patients were then spiked with a clinical dosage of ticagrelor (3 μM—approximately equivalent to a loading dose of 180 mg ticagrelor). Sensitivity was determined using LTA and 5 μM ADP as a platelet agonist. Patients with ≥46% maximal platelet aggregation were considered ticagrelor non-sensitive. Results: Of the 38 CAD patients taking 81 mg ASA, 32% (12/38) were non-sensitive to their 81 mg ASA therapy. All 38 of the recruited patients (100%) were sensitive to ticagrelor ex vivo. In conclusion, we were able to identify ASA non-sensitivity using LTA and determine that ASA non-sensitive patients were sensitive to ticagrelor. Conclusions: Our results suggest that ticagrelor is a promising alternative therapy for patients who are non-sensitive to ASA.

Plateletworks® as a Point-of-Care Test for ASA Non-Sensitivity

“…ASA non-sensitivity has become a well-known and prevalent issue, with anywhere between 20 and 30% of patients at risk of further adverse cardiovascular events due to the failure of ASA to completely inhibit platelet aggregation. Previous studies have reported that 15% of patients with atherosclerotic vascular disease were non-sensitive to their prescribed 81 mg ASA therapy, and a further 32% of patients with cardiovascular risk factors were also non-sensitive to ASA [ 11 , 12 ]. There are two main mechanisms of ASA non-sensitivity: (1) pharmacokinetic variability in patients’ response to ASA—for example reduced absorption within the gastrointestinal tract, higher ASA metabolism, or increased platelet turnover; (2) pharmacodynamic differences such as genetic polymorphisms leading to structural changes in the COX enzyme [ 25 ].…”

“…The Antithrombotic Trialists Collaboration demonstrated that ASA is effective in reducing adverse cardiovascular events by approximately 20% [ 6 ]. However, an alarming 20–30% of patients with atherosclerotic disease suffer from ASA non-sensitivity, where ASA fails to prevent adverse cardiovascular events [ 7 , 8 , 9 , 10 , 11 , 12 ].…”

Low-dose aspirin and rivaroxaban combination therapy to overcome aspirin non-sensitivity in patients with vascular disease

“…LTA was conducted as described above. Patients were considered aspirin non-sensitive if they had a maximal platelet aggregation of ≥20% when activated with arachidonic acid, as per previous studies ( 8 , 13 – 17 , 20 , 21 ).…”

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

“…It has been documented that ~20–30% of patients are resistant to their aspirin therapy, with some studies determining resistance to be as high as 60% in their respective patient population [ 36 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. Recent studies suggest that aspirin resistance increases the risk of adverse cardiovascular events by almost three-fold in various patient populations [ 38 , 46 , 52 ].…”

“…In LTA analysis, light transmission is proportional to platelet aggregation and hence can provide the total percentage of platelets aggregated in response to the platelet agonist of interest. LTA can be a useful method for invitro platelet testing, as a wide range of platelet activation pathways can be investigated using different agonists such as arachidonic acid, ADP, and thrombin, and plasma samples can be incubated with drugs of interest before testing in order to study the effects of these drugs on platelet aggregation [ 51 , 58 ]. Therefore, in patients taking antiplatelets, aggregation is expected to remain around 0%, and those who are not taking any antiplatelet therapy, the light transmission is expected to increase to approximately 100% [ 59 , 60 ]…”