cangrelor and Stroke

New P2Y12 inhibitors can be classified as oral (prasugrel and ticagrelor) and intravenous drugs (cangrelor and elinogrel). These P2Y12 inhibitors might be superior to clopidogrel for reducing ischemic events in patients with coronary artery disease (CAD). We performed a meta-analysis of randomized trials that compared new oral or intravenous P2Y12 inhibitors with clopidogrel to determine their efficacy and safety in patients.. Twelve randomized, placebo-controlled studies and two subgroup analyses of included studies on ST-segment elevation myocardial infarction (STEMI) were included. The database consisted of 82,784 patients, with 43,875 (53%) on new oral P2Y12 inhibitors and 38909 (47%) on intravenous P2Y12 inhibitors compared with clopidogrel. The primary efficacy endpoint was major adverse cardiac events (MACEs). The primary safety endpoint was thrombolysis in myocardial infarction (TIMI) major bleeding. New oral P2Y12 inhibitors significantly decreased MACEs (odds ratio: 0.85, p<0.0001 for the whole cohort; OR: 0.77, p=0.04 for STEMI) and all-cause death (OR: 0.88, p=0.04 for the whole cohort; OR: 0.77, p=0.01 for STEMI). Among new intravenous P2Y12 inhibitors, only cangrelor significantly decreased the risk of MACEs. An increase in TIMI major bleeding was observed only by prasugrel among the new P2Y12 inhibitors.. New oral P2Y12 inhibitors reduce ischemic events, but there is no obvious increase in major bleeding in patients with CAD, and the risk/benefit ratio is particularly favorable for STEMI patients. Moreover, only cangrelor is beneficial for ischemic events in patients on new intravenous P2Y12 inhibitors.

Topics: Acute Coronary Syndrome; Adenosine; Adenosine Monophosphate; Administration, Oral; Clopidogrel; Coronary Artery Disease; Coronary Restenosis; Fibrinolytic Agents; Hemorrhage; Humans; Injections, Intravenous; Multicenter Studies as Topic; Myocardial Infarction; Piperazines; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Quinazolinones; Randomized Controlled Trials as Topic; Stents; Stroke; Sulfonamides; Thiophenes; Thrombolytic Therapy; Ticagrelor; Ticlopidine

Topics: Adenosine Monophosphate; Aspirin; Clinical Trials as Topic; Dipyridamole; Drug Therapy, Combination; Humans; Platelet Aggregation Inhibitors; Risk; Stroke; Treatment Outcome

Dual antiplatelet therapy (DAP) is necessary to prevent thromboembolic events during carotid stenting, stent-assisted coil embolization, and implant of flow diverters (FD). However, DAP in the acute phase may be challenging. An intravenous alternative, cangrelor, has rapid onset, short plasma half-life, and more reliable antiplatelet action for acute interventions. The study objective was to evaluate feasibility and safety of IV cangrelor during acute neuroendovascular surgery procedures.. We performed a retrospective analysis of our database of patients treated with stent-assisted coil embolization, FD placement for aneurysmal subarachnoid hemorrhage (aSAH), or stenting for acute internal carotid artery (ICA) occlusion where IV cangrelor was used. Morbidity, mortality, incidence of thromboembolic events, hemorrhages, and 90-day outcomes were reported.. Ten patients were found in our database from June 2018 through January 2019. Four patients had aSAH, four had middle cerebral artery strokes with tandem lesions, one had an ICA occlusion, and one had a vertebral artery aneurysm. One of the ten patients experienced a thrombotic event. One patient developed new post-procedural bleeding and two had worsening intracranial hemorrhage. Five patients were discharged home in stable condition, two to acute rehabilitation, one to a nursing facility, and two others expired (likely the result of the severe and evolving strokes). Of the eight who were discharged, six (75%) had a good 90-day functional outcome (modified Rankin Scale 0-2).. Acute administration of IV cangrelor with or without oral ticagrelor is a feasible antiplatelet treatment option for acute neuroendovascular procedures.

Topics: Adenosine Monophosphate; Administration, Intravenous; Administration, Oral; Adult; Aged; Aged, 80 and over; Clopidogrel; Endovascular Procedures; Female; Humans; Male; Middle Aged; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Self Expandable Metallic Stents; Stroke; Subarachnoid Hemorrhage; Ticagrelor; 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

Rescue endovascular and pharmacologic approaches are increasingly being adopted after recanalization failure of acute large-vessel occlusion strokes with mechanical thrombectomy, with encouraging results. The safety and efficacy of glycoprotein IIb/IIIa inhibitors in ischemic stroke have been investigated, though cangrelor, a recent intravenous P2Y12-receptor inhibitor with a rapid onset/offset of action and a short half-life, may be a valuable option. We compared the safety and efficacy of cangrelor with those of glycoprotein IIb/IIIa inhibitors for refractory occlusions.. We performed a retrospective analysis of the ongoing prospective, multicenter, observational Endovascular Treatment in Ischemic Stroke Registry in France between May 2012 and February 2020. Refractory intracranial occlusions of the anterior and posterior circulation were included and defined as recanalization failure of large-vessel occlusion stroke, perioperative target artery reocclusion, or high risk of early reocclusion related to an arterial wall lesion. The primary end point was a favorable outcome, defined as a 90-day mRS of 0-2. Secondary end points were reperfusion, intracranial hemorrhage, and procedural complications.. Among 69 patients, 15 were treated with cangrelor, and 54, with glycoprotein IIb/IIIa inhibitors. The favorable outcome (adjusted OR = 2.22; 95% CI, 0.42-11.75;. Cangrelor seems to be as safe as glycoprotein IIb/IIIa inhibitors for managing refractory intracranial occlusion and leads to satisfactory brain reperfusion. Cangrelor is a promising agent in this setting, and additional studies are warranted to confirm our findings.

Topics: Adenosine Monophosphate; Humans; Prospective Studies; Retrospective Studies; Stroke; Thrombectomy; Treatment Outcome

Acute myocardial infarction (AMI) complicating ischemic stroke is a well known and undertreated event. A conservative management is not infrequent in these settings, due to the fear of hemorrhagic complications related to antithrombotic therapy. Notably, an invasive approach with a primary percutaneous coronary intervention (PCI) has been shown to be associated with a lower in-hospital mortality in patients with concomitant ischemic stroke and AMI. The optimal antiplatelet regimen in these cases has been not clearly defined, yet. We report two cases of patients with AMI complicating ischemic stroke, successfully treated with cangrelor infusion, which was started during PCI and maintained up to 48 h at bridge therapy dosage (0.75 mcg/kg/min). Both patients underwent successful PCI in the acute phase, and neither ischemic nor hemorrhagic complications occurred during in-hospital stay.

Topics: Adenosine Monophosphate; Aged; Aged, 80 and over; Biomarkers; Disease Management; Female; Humans; Male; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Stroke; Time-to-Treatment; Tomography, X-Ray Computed; Treatment Outcome

Treatment of acute cerebrovascular pathology, such as acute ischemic stroke or intracranial aneurysms, presents a challenge if an extracranial or intracranial stent is required; immediate platelet inhibition is vital. To date, there is no standardized approach for antiplatelet inhibition in an acute setting.. To report our preliminary experience and lessons learnt using cangrelor in acute neurointervention.. A single-arm pilot study was performed to assess the safety and efficacy of cangrelor plus aspirin for platelet inhibition in patients who require acute stenting in the setting of neuroendovascular treatment.. Eight patients were enrolled between October 2017 and August 2018. Median age was 71 years (53-86). Seven patients were treated in an acute setting according to the stroke protocol at our institution, while one patient was treated for a symptomatic, unruptured aneurysm with flow diversion and coiling. At admission, the median National Institutes of Health Stroke Scale score for the patients with stroke was 12.5 (range 2-22.3). Cangrelor was infused and all patients achieved adequate platelet inhibition (<200 PRU (P2Y12 reaction units)). Six of seven patients with ischemic stroke had a carotid stent placed and one had an intracranial stent deployed in the middle cerebral artery. None of the patients experienced intraprocedural thromboembolic complications, intraprocedural in-stent thrombosis, hemorrhagic complications, or stroke within 24 hours after the intervention. The majority of patients (6/8) had a good clinical outcome at discharge (modified Rankin Scale score 0-2).. Our findings suggest that cangrelor is a promising alternative in acute stenting for the treatment of cerebrovascular pathology. However, further studies with larger samples are required to accurately elucidate its safety and effectiveness in neuroendovascular procedures.

Topics: Adenosine Monophosphate; Adult; Aged; Aged, 80 and over; Aspirin; Brain Ischemia; Drug Therapy, Combination; Endovascular Procedures; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pilot Projects; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Stents; Stroke; Thrombectomy; Treatment Outcome

Cangrelor is a potent intravenous adenosine diphosphate-receptor antagonist that in the CHAMPION trials reduced the 48-hour and 30-day rates of ischemic events during percutaneous coronary intervention without an increase in severe bleeding.. CHAMPION PCI (A Clinical Trial to Demonstrate the Efficacy of Cangrelor), CHAMPION PLATFORM (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition), and CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention) were 3 randomized, double-blind, double-dummy trials in which cangrelor was compared with clopidogrel during percutaneous coronary intervention. The effect of cangrelor on ischemic events and bleeding was analyzed in the subgroup of patients with a history of cerebrovascular events at least 1 year prior to randomization; the Breslow-Day test was used to test for interaction of treatment effect in subgroups with and without such a history. The primary efficacy end point was a composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours. Among 24 910 randomized patients, 1270 patients (5.1%) had a cerebrovascular event >1 year old, including 650 assigned to cangrelor and 620 assigned to clopidogrel. Consistent with the overall trial results, the rate of the primary efficacy end point was 4.3% in the cangrelor group versus 5.3% in the clopidogrel group (odds ratio 0.80; 95% confidence interval 0.48-1.34; P=0.40; P for interaction =0.97), and the rate of GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding was 0.3% in both groups (P=0.97; P for interaction =0.81).. Among patients in the CHAMPION trials with a prior cerebrovascular event at least 1 year before the percutaneous coronary intervention, the efficacy and bleeding profile of cangrelor compared with clopidogrel was similar to that in the overall trial.

Topics: Adenosine Monophosphate; Aged; Brain Ischemia; Chi-Square Distribution; Clopidogrel; Coronary Artery Disease; Coronary Thrombosis; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Logistic Models; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Stroke; Ticlopidine; Time Factors; Treatment Outcome