Aspirin Resistance Affects Medium-Term Recurrent Vascular Events after Cerebrovascular Incidents: A Three-Year Follow-up Study

Abstract

Background: The aim of this prospective, a three-year follow-up study, was to establish the role of high on-treatment platelet reactivity (HTPR) in predicting the recurrence of vascular events in patients after cerebrovascular incidents, particularly in the aspect of stroke etiology. Methods:The study included 101 subjects with non-embolic cerebral ischemia (69 patients with ischemic stroke and 32 patients with transient ischemic attack) treated with 150 mg of acetylsalicylic acid (aspirin) a day. The platelet reactivity was tested in the first 24 h after the onset of cerebral ischemia by impedance aggregometry. Recurrent vascular events, including recurrent ischemic stroke, transient ischemic attack, myocardial infarction, systemic embolism, or sudden death of vascular reason, were assessed 36 months after the onset of cerebral ischemia. Results: Recurrent vascular events occurred between 3 and 9 months after onset in 8.5% of all subjects; in the HTPR subgroup, recurrent vascular events occurred in 17.9%; in the normal on-treatment platelet reactivity (NTPR) subgroup, they occurred in 4.6%. We did not notice early or long-term recurrent events. Aspirin resistant subjects had a significantly higher risk of recurrent vascular events than did aspirin sensitive subjects (Odds ratio (OR) = 4.57, 95% Confidence interval (CI) 1.00-20.64; p = 0.0486). Cox proportional hazard models showed that large-vessel disease (Hazard ratio (HR) 12.04, 95% CI 2.43-59.72; p = 0.0023) and high on-treatment platelet reactivity (HR 4.28, 95% CI 1.02-17.93; p = 0.0465) were independent predictors of recurrent vascular events. Conclusion: Aspirin resistance in the acute phase of cerebral ischemia was associated with a higher risk of recurrent medium-term vascular events, coexisting with large-vessel etiology of stroke. Platelet function-guided personalized antiplatelet treatment should be considered for patients with recurrent strokes, especially when due to large-vessel disease.

The Phenomenon of Clopidogrel High On-Treatment Platelet Reactivity in Ischemic Stroke Subjects: A Comprehensive Review

“…The most common event is another recurrent stroke or transient ischemic attack, but stroke subjects are also at a higher risk of myocardial infarction (MI), sudden cardiac death, acute limb ischemia, or systemic embolism. Previous studies regarding aspirin resistance have demonstrated a significant, independent association between high on-treatment platelet reactivity and a higher risk of recurrent vascular events in stroke subjects [51]. The data on clopidogrel therapy are consistent.…”

Multifactorial Background for a Low Biological Response to Antiplatelet Agents Used in Stroke Prevention

“…The mechanisms leading to a low biological response to antiplatelet agents and the incidence of aspirin and clopidogrel resistance are similar, both in ischemic stroke and coronary heart disease. A significant negative impact of the phenomenon on many clinical aspects in both diseases was reported, including a severe clinical course, poor early and late prognosis, an unfavorable clinical outcome, and a higher risk of recurrent vascular events [ 50 , 51 , 52 ].…”

Platelet function‐guided antiplatelet therapy in stroke prevention

“…In our next study we underlined that stroke subjects with large vessel disease and high on‐aspirin platelet reactivity have significantly larger volume of acute ischaemic infarct and severity of chronic ischaemic lesions compared with normal on‐aspirin platelet reactivity strokes 5 . We also emphasised that stroke subjects with aspirin nonresponsiveness are more likely to develop medium‐term (3 to 9 months) recurrent vascular events, in particular the next ischaemic stroke 6 . The above findings undoubtedly suggest a negative impact of aspirin ineffectiveness on poor clinical outcome, in particular among smoking males with large vessel disease as a cause of stroke.…”

“…5 We also emphasised that stroke subjects with aspirin nonresponsiveness are more likely to develop medium-term (3 to 9 months) recurrent vascular events, in particular the next ischaemic stroke. 6 The above findings undoubtedly suggest a negative impact of aspirin ineffectiveness on poor clinical outcome, in particular among smoking males with large vessel disease as a cause of stroke. Moreover, our findings regarding aspirin are consistent with the results obtained by other authors.…”