Vorapaxar as an Alternative for Ticagrelor Resistance in Neuroendovascular Intervention

BACKGROUND Perioperative dual‐antiplatelet therapy for flow diversion limits thromboembolic complications. However, resistance to dual‐antiplatelet therapy medications remains a concern for neuroendovascular intervention. To date, there is no standardized approach for resistance to ADP receptor antagonists. METHODS We report a case of ticagrelor resistance for flow diversion of an intracranial aneurysm treated with vorapaxar, as well as a narrative review of the literature for previous cases of ticagrelor resistance. RESULTS Flow diversion with the Pipeline embolization device was deployed for a left internal carotid artery blister aneurysm and bilateral internal carotid artery dissecting pseudoaneurysms. The patient had 3 thromboembolic complications while on dual‐antiplatelet therapy with ticagrelor or prasugrel, leading to transition of antiplatelet therapy to vorapaxar. At 84 days follow‐up, the patient was fully recovered with complete occlusion of the aneurysms. CONCLUSION Our case suggests that vorapaxar is a promising alternative for patients with ticagrelor resistance in flow diversion–treated intracranial aneurysms. High‐quality randomized controlled trials are needed to elucidate the safety and efficacy of vorapaxar in neuroendovascular procedures.

ADP-receptor antagonists in patients with acute myocardial infarction complicated by cardiogenic shock: a pooled IABP-SHOCK II and CULPRIT-SHOCK trial sub-analysis

Purpose The purpose of this pooled analysis is to compare the clinical outcome of patients with acute myocardial infarction complicated by cardiogenic shock treated with either clopidogrel or the newer, more potent ADP-receptor antagonists prasugrel or ticagrelor. Patients from the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) and Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) trial were included. Methods and results For the current analysis, the primary endpoint was 1-year mortality and the secondary safety endpoint was moderate or severe bleedings until hospital discharge with respect to three different ADP-receptor antagonists. Eight hundred fifty-six patients were eligible for analysis. Of these, five hundred seven patients (59.2%) received clopidogrel, one hundred seventy-eight patients (20.8%) prasugrel and one hundred seventy-one patients (20.0%) ticagrelor as acute antiplatelet therapy. The adjusted rate of mortality after 1-year did not differ between prasugrel and clopidogrel (hazard ratio [HR]: 0.81, 95% confidence interval [CI] 0.60–1.09, padj=0.17) or between ticagrelor and clopidogrel treated patients (HR: 0.86, 95% CI 0.65–1.15, padj=0.31). In-hospital bleeding events were significantly less frequent in patients treated with ticagrelor vs. clopidogrel (HR: 0.37, 95% CI 0.20–0.69, padj=0.002) and not different in patients treated with prasugrel vs. clopidogrel (HR: 0.73, 95% CI 0.43–1.24, padj=0.24), see Table 1. Conclusion This pooled sub-analysis is the largest analysis on safety and efficacy of three oral ADP-receptor antagonists and shows that an acute therapy with either clopidogrel, prasugrel or ticagrelor is no predictor of 1-year mortality. Treatment with ticagrelor seems to be associated with less in-hospital moderate and severe bleeding events in comparison to clopidogrel. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): German Heart FoundationEuropean Union 7th Framework Program

Clopidogrel vs. prasugrel vs. ticagrelor in patients with acute myocardial infarction complicated by cardiogenic shock: a pooled IABP-SHOCK II and CULPRIT-SHOCK trial sub-analysis

Aims The aim of this pooled sub-analysis of the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) and Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) trial was to compare the clinical outcome of patients with acute myocardial infarction complicated by cardiogenic shock treated either with clopidogrel or the newer, more potent ADP-receptor antagonists prasugrel or ticagrelor. Methods and results For the current analysis the primary endpoint was 1-year mortality and the secondary safety endpoint was moderate or severe bleedings until hospital discharge with respect to three different ADP-receptor antagonists. 856 patients were eligible for analysis. Of these, 507 patients (59.2%) received clopidogrel, 178 patients (20.8%) prasugrel and 171 patients (20.0%) ticagrelor as acute antiplatelet therapy. The adjusted rate of mortality after 1-year did not differ significantly between prasugrel and clopidogrel (hazard ratio [HR]: 0.81, 95% confidence interval [CI] 0.60–1.09, padj = 0.17) or between ticagrelor and clopidogrel treated patients (HR: 0.86, 95% CI 0.65–1.15, padj = 0.31). In-hospital bleeding events were significantly less frequent in patients treated with ticagrelor vs. clopidogrel (HR: 0.37, 95% CI 0.20 -0.69, padj = 0.002) and not significantly different in patients treated with prasugrel vs. clopidogrel (HR: 0.73, 95% CI 0.43 -1.24, padj = 0.24). Conclusion This pooled sub-analysis is the largest analysis on safety and efficacy of three oral ADP-receptor antagonists and shows that acute therapy with either clopidogrel, prasugrel or ticagrelor is no independent predictor of 1-year mortality. Treatment with ticagrelor seems independently associated with less in-hospital moderate and severe bleeding events compared to clopidogrel. This finding might be due to selection bias and should be interpreted with caution. Graphic abstract

Managing Clopidogrel Hypersensitivity without Interrupting Therapy: The Toronto Approach

Clopidogrel remains a widely used antiplatelet agent for patients with established or high risk of atherothrombotic disease, particularly those treated with coronary, carotid or peripheral endovascular stenting. Clopidogrel hypersensitivity is an uncommon but well established adverse drug reaction presenting a challenge for patient management. The clinical presentation ranges from focal or diffuse cutaneous manifestations in most patients to angioedema in some and a systemic immune response in rare cases. The treatment options include drug discontinuation with or without desensitization therapy, switching to alternate ADP receptor antagonists or administration of oral steroids while continuing clopidogrel in patients at high risk of adverse events with clopidogrel discontinuation. In this review the author describes the phenomenon of clopidogrel hypersensitivity, various treatment strategies.