cangrelor and Ischemic-Stroke

Rescue therapies are increasingly used in the setting of endovascular therapy for large-vessel occlusion strokes. Among these, cangrelor, a new P2Y12 inhibitor, offers promising pharmacologic properties to join the reperfusion strategies in acute stroke. We assessed the safety and efficacy profiles of cangrelor combined with endovascular therapy in patients with large-vessel-occlusion stroke.. We performed a retrospective patient data analysis in the ongoing prospective multicenter observational Endovascular Treatment in Ischemic Stroke Registry in France from July 2018 to December 2020 and conducted a systematic review and meta-analysis using several data bases. Indications for cangrelor administration were rescue strategy in case of refractory intracranial occlusion with or without intracranial rescue stent placement, and cervical carotid artery stent placement in case of cervical occlusion (tandem occlusion or isolated cervical carotid occlusion).. In the clinical registry, 44 patients were included (median initial NIHSS score, 12; prior intravenous thrombolysis, 29.5%). Intracranial stent placement was performed in 54.5% (. Cangrelor offers promising safety and efficacy profiles, especially considering the complex endovascular reperfusion procedures in which it is usually applied. Further large prospective data are required to confirm these findings.

Topics: Adenosine Monophosphate; Cerebral Hemorrhage; Combined Modality Therapy; Endovascular Procedures; Humans; Ischemic Stroke; Thrombectomy; Treatment Outcome

Cangrelor is an intravenous P2Y12 receptor inhibitor with a rapid onset/offset of action and a short half-life (3-6 min). The objective was to present a preliminary experience regarding the safety and effectiveness using cangrelor, in combination with aspirin, in acute ischemic stroke patients requiring acute stenting.. Retrospective analysis for patients who underwent stenting (intracranial and/or extracranial) in the setting of acute ischemic stroke with cangrelor and aspirin as antiplatelet therapy.. Cangrelor was used in 12 patients, 4 (33%) with extracranial stenting, 6 (50%) with intracranial stenting and 2 (17%) with combined extracranial and intracranial stenting. The mean age was 67 years (44-88) and 9 patients (75%) were female. The median National Institutes of Health Stroke Score at admission was 15 (IQR: 8-22). Of the patients, six (50%) received intravenous thrombolysis. All patients (100%) obtained modified thrombolysis in cerebral infarction score ≥2b. Good clinical outcome, defined as modified Rankin scale score ≤2 at 3‑months follow-up, was observed in 7 patients (58%). None of the patients experienced intraprocedural thromboembolic complications. Postprocedural stent thrombosis after cessation of cangrelor infusion due to emergency craniotomy surgery to manage malignant cerebral infarction occurred in one patient (8%). Of the patients, two (17%) experienced asymptomatic intracranial hemorrhage (ICH), one patient (8%) experienced symptomatic ICH and one (8%) retroperitoneal hematoma was observed, which was managed conservatively.. Cangrelor might be a safe and effective antiplatelet medication owing to its on/off activity for acute stenting in the setting of acute ischemic stroke. Further investigations through randomized studies with larger samples are necessary.

Topics: Adenosine Monophosphate; Adult; Aged; Aged, 80 and over; Brain Ischemia; Female; Humans; Ischemic Stroke; Male; Middle Aged; Retrospective Studies; Stents; Thrombectomy; Treatment Outcome

Guidelines for antiplatelet therapy administration, during emergent stenting for extra-cranial internal carotid artery (EC-ICA) occlusion in the setting of acute ischemic stroke (AIS) are lacking. Different antiplatelet regimen are used in association to endovascular therapy (EVT) for the treatment of EC-ICA lesions. We aimed to compare the clinical and radiological effects of three intravenous antiplatelet agents used during emergent EC-ICA stenting.. Clinical data were collected from January 2015 to December 2019 in a monocentric prospective registry of AIS patients treated by EVT. All patients who underwent emergent EC-ICA stenting were sorted regarding the intravenous antiplatelet agent used during the procedure.. Among 218 patients treated by EVT for an EC-ICA occlusion of the anterior circulation during the study period, 70 underwent an emergent stenting of the EC-ICA. 60 were included in the present study, 9 received intravenous (IV) Cangrelor, 8 IV abciximab and 43 Aspirin. The rate of favorable neurological outcome, defined as modified Rankin Scale (mRS) ≤ 2 at three months were better in the Cangrelor and Aspirin groups (66,7% and 58,1%, respectively) than in the Abciximab group (37,5%), as well as, the rate of any intracranial ICH (22,2% and 37,2% vs 62,5%). The rate of acute stent reocclusion was similar between groups.. When used as a rescue treatment during emergent stenting of EC-ICA, Cangrelor and Aspirin present a better safety profile than Abciximab, with less intracranial hemorrhages and a higher rate of good clinical outcome. Additional studies are needed to confirm these findings.

Topics: Abciximab; Adenosine Monophosphate; Administration, Intravenous; Aged; Aspirin; Carotid Artery, Internal; Carotid Stenosis; Drug Administration Schedule; Emergencies; Endovascular Procedures; Female; Humans; Ischemic Stroke; Male; Middle Aged; Platelet Aggregation Inhibitors; Registries; Retrospective Studies; Stents; Time Factors; Treatment Outcome

The inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-activating peptide (AP)-induced platelet aggregation have not been fully elucidated. The present study aimed to investigate the inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-AP-induced platelet aggregation using platelet-rich plasma (PRP) from individuals including patients with stroke or transient ischemic attack (TIA).. PRP was given to 10 healthy individuals pretreated in vitro with cangrelor, then stimulated with adenosine diphosphate (ADP), PAR4-AP, or PAR1-AP. Moreover, 20 patients were enrolled from 148 consecutive patients with acute ischemic stroke or TIA admitted to our institute between December 2017 and April 2019. PRP obtained from each patient before and >7 days after initiation of clopidogrel was similarly stimulated with these agonists. Platelet aggregation was measured using an automatic coagulation analyzer in all participants.. In healthy individuals, ADP- and PAR4-AP-induced platelet aggregations were significantly inhibited depending on the cangrelor concentration in vitro, while PAR1-AP-induced platelet aggregation was slightly inhibited. In patients with stroke or TIA, clopidogrel inhibited ADP-induced platelet aggregation at all concentrations, and significantly inhibited PAR4-AP-induced platelet aggregation at 50 µmol/L of PAR4-AP (p<0.05), especially in 5 patients who showed high reactivity to PAR4-AP. PAR1-AP-induced platelet aggregation was also slightly inhibited.. We showed significant inhibitory effects on PAR4-AP-induced platelet aggregation by clopidogrel in patients with stroke or TIA who had high reactivity to PAR4-AP.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adult; Aged; Aged, 80 and over; Blood Platelets; Case-Control Studies; Clopidogrel; Female; Humans; Ischemic Attack, Transient; Ischemic Stroke; Male; Middle Aged; Oligopeptides; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Predictive Value of Tests; Prospective Studies; Purinergic P2Y Receptor Antagonists; Treatment Outcome

Emergent stenting of both extra- and intracranial occlusions during acute ischemic stroke procedures is complicated by the need for immediate platelet inhibition to prevent thromboembolic complications. IV cangrelor is a relatively new antiplatelet that was initially approved for coronary interventions. Five prior case series have been published evaluating the results of IV cangrelor in neurointerventional procedures. We sought to combine the data from all prior studies and analyze only ischemic stroke interventions.. A prospectively maintained database was reviewed to identify all cases of IV cangrelor administration during acute ischemic stroke intervention. Nine additional patients were identified who have not been previously published. In addition, a literature search was performed to identify five prior publications of cangrelor in neurointervention. The data from these was combined with our institution in a pooled-analysis.. Overall, 129 patients who received IV cangrelor during an acute ischemic stroke intervention were identified. The asymptomatic intracranial hemorrhage rate was 12.6%(11/87). The symptomatic intracranial hemorrhage rate was 6.2% (8/129). The rate of retroperitoneal hematoma and gastrointestinal bleeding were also low (1.5% and 0.8%, 2/129 and 1/129). There was one case of intraprocedural thromboembolic complication (0.8%) and no cases of intraprocedural in-stent thrombosis(0%).. IV cangrelor during acute ischemic stroke intervention appears to be safe, with a symptomatic intracranial hemorrhage rate of 6.2%. More research is needed to determine the ideal dosing regimen.

Topics: Adenosine Monophosphate; Brain Ischemia; Humans; Ischemic Stroke; Platelet Aggregation Inhibitors; Stents; Stroke; Treatment Outcome

In cases of large-vessel-occlusion strokes due to an underlying tandem internal carotid artery occlusion or intracranial atherosclerotic disease, concomitant stent placement may be needed. Immediate platelet inhibition is necessary, but to date, a standardized approach for antiplatelet inhibition in acute settings is still missing. Here we report our single-center experience about the safety and efficacy of periprocedural administration of cangrelor in patients with acute ischemic stroke due to intracranial or cervical artery occlusion undergoing stent placement.. We retrospectively evaluated all cases of acute ischemic stroke that needed acute stent implantation and were treated with periprocedural administration of cangrelor between January 2019 and April 2020 at our institution. All patients who needed either extracranial or intracranial artery stent placement (in either the anterior or posterior circulation) were included.. We evaluated 38 patients in whom cangrelor was administered IV periprocedurally. Their mean age was 64 years (range, 26-85 years), with 25/38 male subjects and 13/38 female patients. In 26 patients (68.4%), a tandem occlusion was present and was treated with carotid artery stent placement, while 12 patients (31.6%) required an intracranial stent implantation. In 4 subjects (10.5%), an intracerebral hemorrhage occurred after the procedure. All patients in the series were alive 1 week after the procedure.. Although larger, multicentric randomized studies are strongly warranted, our results support the hypothesis of a possible role of cangrelor as a valuable therapeutic option in the management of platelet inhibition in acute ischemic stroke procedures after intra- or extracranial stent placement.

Topics: Adenosine Monophosphate; Adult; Aged; Aged, 80 and over; Arterial Occlusive Diseases; Carotid Artery, Internal; Cerebral Hemorrhage; Endovascular Procedures; Female; Humans; Ischemic Stroke; Male; Middle Aged; Platelet Aggregation Inhibitors; Retrospective Studies; Stents; Thrombectomy; Treatment Outcome