Enhanced Platelet Reactivity under Aspirin Medication and Major Adverse Cardiac and Cerebrovascular Events in Patients with Coronary Artery Disease

Abstract

Aspirin is indispensable in secondary prevention of ischemic events in patients with coronary artery disease (CAD). However, insufficient platelet inhibition despite aspirin medication is frequent. This is referred to as high on-treatment platelet reactivity (HTPR). Nevertheless, if this is associated with clinical outcome instead of only laboratory phenomenon remains unclear so far. In this study, we test whether patients with ischemic events have higher platelet reactivity despite aspirin medication than patients without ischemic events. In this prospective study of 72 CAD patients, we determined pharmacodynamic response to aspirin by arachidonic acid induced aggregation via light-transmission aggregometry and expressed as maximum of aggregation (MoA). During a mean follow-up duration of 3.2 years, major adverse cardiac and cerebrovascular events (MACCE), mortality, non-ST-elevation myocardial infarction (NSTEMI), and stroke were assessed as endpoints via yearly telephone interviews with the treating physician of the patients. Patients who suffered from MACCE, death, and NSTEMI had a significantly higher MoA than those without (MACCE: 5.4 vs. 16.4%, <i>p</i> < 0.05; death: 5.6 vs. 16.8%, <i>p</i> < 0.05; NSTEMI: 1.8 vs. 21%, <i>p</i> < 0.001). MoA did not differ with regard to the occurrence of stroke (10.1 vs. 14.9%, <i>p</i> = 0.59). Patients with MACCE, death, and NSTEMI show enhanced platelet reactivity despite aspirin medication as compared to patients without ischemic events. Hence, insufficient response to aspirin medication should be regarded as risk factor for ischemic events in CAD patients. Further trials are needed to assess options to overcome HTPR to aspirin.

P2Y12 inhibitors in neuroendovascular surgery: An opportunity for precision medicine

“…12 Genotyping aspirin resistance, however, has gained attention, i.e., for the genetic polymorphism of the PTGS1 gene that encodes COX-1, as specific short nucleotide polymorphisms and haplotypes dysregulate arachidonic acidinduced thromboxane production leading to inadequate aspirin responses. 13 Aspirin HPR, a risk factor for major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI), 14 is observed in up to 15% of patients undergoing neuroendovascular interventions; however, in alignment with cardiovascular studies, a consistent association of aspirin PR and clinical outcomes is not evident. However, two recent metaanalyses suggest that in DAPT, low-dose (150 mg daily) as compared to high-dose aspirin given either before or after the neuroendovascular intervention increases late (>6 months) thromboembolism by about 2.5 times without differences in hemorrhagic events.…”

MTX Treatment Does Not Improve Outcome in Mice with AMI

“…However, this is not surprising as it has been shown that a primarily thrombocytopenia under MTX is followed by a phase of thrombocytosis [40]. Platelet reactivity is known to be associated with cardiovascular events [41]. Hence, this might have influenced outcome in a counterbalanced way after AMI as well.…”

MicroRNA as Potential Biomarkers of Platelet Function on Antiplatelet Therapy: A Review

“…Several possible causes were put forward to explain the phenomenon of ischemic events in patients on antiplatelet treatment, such as genetic polymorphisms, drugdrug interactions, or HTPR (Buonamici et al, 2007;Russo et al, 2016). HTPR observed during both ASA and P2Y 12 receptor antagonists therapy was associated with a higher risk of adverse cardiovascular events (Buonamici et al, 2007;Aradi et al, 2010;Dannenberg et al, 2020). As was previously described, miRNAs are able to modify the expression of platelet proteins by targeting mRNAs and thereby altering their biochemical pathways including those associated with drug response.…”

“…It is worth noting that many factors may increase the risk of MACE, but the mechanisms of correlations between miRNAs, platelet reactivity, and MACE are not clear. The risk of cardiovascular events can be heightened due to a number of factors, i.e., HTPR (Buonamici et al, 2007;Aradi et al, 2010;Dannenberg et al, 2020). However, miRNAs might also influence the transcription of specific genes and lead to the abnormalities of the process of hemostasis, thrombosis, and antiplatelet drug response (Teruel-Montoya et al, 2015;Parker et al, 2020).…”