Background

Ticagrelor is a recent antiplatelet agent that reversibly inhibits the ADP P2Y12 receptor [1]. It is widely used in the treatment of coronary acute syndromes [2]. The literature on intravenous thrombolysis for ischemic stroke in patients taking ticagrelor is limited to eight cases [3-7]. Two cases of symptomatic intracranial hemorrhage, one case of asymptomatic intracranial hemorrhage and one case of retropharyngeal hematoma have been reported [3-5].

Since the SOCRATES [8] and THALES [9] trials, interest for ticagrelor in secondary prevention of minor stroke or transient ischemic attack has emerged. The use of ticagrelor following moderate or severe acute ischemic stroke is presumed to be a safe option according one retrospective study [10].

The number of patients who suffer acute ischemic strokes while taking ticagrelor is likely to increase in the future. However, the eligibility for intravenous thrombolysis remains controversial. According to international stroke guidelines, the use of intravenous thrombolysis in acute ischemic stroke treatment is recommended notwithstanding a single or dual antiplatelet therapy pretreatment [11]. However, no study has investigated the safety of intravenous thrombolysis in patients taking ticagrelor.

We present a case of intravenous thrombolysis in an acute stroke patient taking ticagrelor for an ST-segment elevation myocardial infarction.A literature review for intravenous thrombolysis in acute ischemic stroke patients pretreated with ticagrelor was conducted by searching PubMed using the keywords stroke, intravenous thrombolysis and ticagrelor.

Case Presentation

We present a 57-year-old patient who was hospitalized for ST-segment elevation myocardial infarction and treated by ticagrelor (90mg) twice daily. Upon admission, he underwent percutaneous coronarography showing severe tritronic atheromatosis.

Four days later, he developed sudden right hemiparesis and mutism. His National Institutes of Health Stroke Scale (NIHSS) was 12 for right facial weakness, right hemiparesis, mutism, partial alteration of consciousness and partial gaze palsy. Brain computed tomography did not demonstrate any acute ischemic damage (Figure 1). He received 0.9 mg/kg intravenous alteplase 15 minutes after symptoms were discovered and was last seen asymptomatic 90 minutes prior to discovery. 24 hours after intravenous thrombolysis, his NIHSS score improved to 1 (mild dysarthria) and brain CT demonstrated left frontal hypodensity without hemorrhage (Figure 2). A magnetic resonance imaging six days later demonstrated left frontal infraction (Figure 3). Aspirin therapy at 80 mg once a day was started and ticagrelor was continued at 90 mg twice daily. He was eventually discharged home with mild aphasia as his only neurological deficit (NIHSS: 1).

Figure 1: Initial brain computed tomography.

Figure 2: 24-hour post intravenous thrombolysis computed tomography demonstrating a left frontal hypodensity without hemorrhage.

Figure 3: Magnetic resonance imaging six days later demonstrating left frontal infraction with a hyperintensity on axial diffusion (A) and axial FLAIR (B) sequencies.

The patient had no residual neurological deficits at a 1-year follow up.

Discussion and Conclusions

A literature review for intravenous thrombolysis in acute ischemic stroke patients pretreated with ticagrelor was conducted by searching PubMed using the keywords stroke, intravenous thrombolysis and ticagrelor. Only eight cases have been described to date [3-7]. The main characteristics of each patient are illustrated in Table 1. Three of them developed clinical complications, two deadly hemorrhagic transformations (Godier et al. 2015; Lo et al. 2016) and one retropharyngeal hematoma (Lo et al. 2016) while one patient presented an asymptomatic intraparenchymal hemorrhage (Wright et al. 2019). Each of those cases involved the anterior cerebral circulation. Our case is the second patient taking ticagrelor who was treated by intravenous thrombolysis for an anterior circulation ischemic stroke without complication. It is worth noting that only one case also benefited from mechanical thrombectomy (Rizzo et al. 2021). Onset to needle time is missing in three patients (Godier et al. 2015; Lo et al. 2016).

Table 1: Main characteristics of published cases of intravenous thrombolysis in acute ischemic stroke.

The increasing use of ticagrelor raises the question of intravenous thrombolysis eligibility in case of acute ischemic stroke. According to international stroke guidelines, intravenous thrombolysis for acute ischemic stroke treatment is recommended notwithstanding single or dual antiplatelet therapy pretreatment [12]. Conflicting data exists on the safety of intravenous thrombolysis for acute ischemic stroke in patients taking dual antiplatelet therapy [13,14]. A recent meta-analysis demonstrated that the increase in symptomatic intracranial hemorrhage and mortality initially reported does not persist after adjusting for confounding variables [15]. Pending further studies on the safety of intravenous thrombolysis in patients taking ticagrelor, such decisions must be made on a case-by-case basis.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent for publication was obtained from the patient.

Availability of data and materials

Not applicable. 

Competing interests

The authors declare that they have no competing interests.

Funding

Not applicable.

Authors' contributions

L.P. is the main writer. L.P. was in charge the patient during the hospitalization and performed the literature review. E.L. was in charge of the patient during the hospitalization and commented the article. C.R. performed the literature review and commented the article. M.D. was in charge of the patient during the hospitalization and commented the article. J.E. was in charge of the patient during the hospitalization and commented the article.

Acknowledgements

Not applicable.

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