Prior Antiplatelet Agent Use and Outcomes after Intravenous Thrombolysis with Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke: A Meta-Analysis of Cohort Studies and Randomized Controlled Trials

Abstract

In acute ischemic stroke patients receiving intravenous recombinant tissue plasminogen activator therapy, prior antiplatelet agent use did not lead to a significant difference in functional outcome, although it significantly increased the risk of symptomatic intracranial hemorrhage. Recanalization rate was not different between two groups. In the subgroup analysis, prior clopidogrel mono therapy may not increase the risk of symptomatic intracranial hemorrhage, which will need further studies to confirm.

Low- Versus Standard-Dose Alteplase in Patients on Prior Antiplatelet Therapy

“…Additionally, Pan et al 6 did not demonstrate increased recanalization rate in patients on prior APT in their meta-analysis. In ENCHANTED trial, more patients in the prior APT group had atrial fibrillation and a final diagnosis of cardioembolic stroke, features which may suggest a lower efficacy of low-dose alteplase because of proximal vessel occlusion and greater clot burden.…”

“…24 Another important aspect of APT in AIS relates to the type, number, and combination of prior agents for which the data are scarce, but a significant dose response in relation to the number of antiplatelet agents prescribed has been reported. 5,6 A higher sICH risk was noted in thrombolysis-treated patients on combination therapy, in particular aspirin and clopidogrel, who were registered in the Virtual International Stroke Trials Archive database. 25 Such an association was also noted in the SITS International Stroke Thrombolysis Register 3 and the Get With the Guidelines registry cohort where the combination aspirin and clopidogrel were associated with a number needed to harm of 60 compared with 147 for aspirin monotherapy.…”

“…5, 6 Pan et al 6 reported that his was associated with a reduced probability of good outcome (odds ratio [OR], 0.86; 95% confidence interval [CI], 0.73-1.01; P=0.06), although others have not reported any clear attenuation of the clinical benefit. 7 However, the ARTIS trial (APT in Combination With Recombinant Tissue Plasminogen Activator in Thrombolysis in Ischemic Stroke), the only randomized trial of de novo aspirin with standard-dose alteplase versus standard-dose alteplase alone, was terminated prematurely because of an excess sICH in the combination arm (absolute difference, 2.8%; 95% CI, 0.2-5.4; P=0.04).…”

Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Receiving Antiplatelet Therapy: A Systematic Review and Meta‐analysis of 19 Studies

“…Numerous efforts have been made by researchers to identify factors that could cause alterations in the efficacy and safety of systemic thrombolysis,5 among which prestroke medications have always been a major area of interest 6. However, it is thus far a disturbing fact—given the large proportion of stroke patients who receive long‐term antiplatelet therapy—that no consensus has been reached on the exact risk‐benefit profile of intravenous thrombolysis in patients taking antiplatelet medications before the onset of stroke.…”

“…Meta‐analyses based on only a limited number of those studies were therefore subject to inaccuracies and biases, because they did not allow us to synthesize adjusted results or to perform comprehensive subgroup analyses 5, 6. Now with data from some of the largest registries having surfaced, our attention is once again brought to the subject of intravenous thrombolysis in patients receiving antiplatelet medications 25, 26, 29.…”