ticagrelor and Arterial-Occlusive-Diseases

An important role for adenosine diphosphate (ADP)-induced platelet activation and aggregation was proposed more than 40 years ago. The clinical use of clopidogrel, a prodrug of an irreversible P2Y (12) antagonist, has further proved the relevance of inhibiting signaling via the platelet-specific P2Y (12) ADP receptor in the prevention of cardiovascular events. Pharmacological studies at AstraZeneca R&D Charnwood have identified direct, selective, and competitive P2Y (12) antagonists, including cangrelor (also known as AR-C69931MX), which is suitable for intravenous administration, and AZD6140, which is suitable for oral administration. In preclinical use, these compounds predictably and effectively inhibited platelet aggregation without significant increases in bleeding time. In clinical use, these compounds may have significant advantages over current antiplatelet agents. This article summarizes preclinical and clinical data on cangrelor and AZD6140 and discusses the potential of these compounds as novel antiplatelet therapies.

Topics: Adenosine; Adenosine Diphosphate; Adenosine Monophosphate; Administration, Oral; Animals; Arterial Occlusive Diseases; Clinical Trials as Topic; Dogs; Double-Blind Method; Drug Evaluation, Preclinical; Female; Fibrinolytic Agents; Humans; Injections, Intravenous; Male; Membrane Proteins; Platelet Aggregation; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Pyridines; Rabbits; Randomized Controlled Trials as Topic; Receptors, Purinergic P2Y12; Thrombosis; Ticagrelor

Given many emerging indications for endovascular interventions in ischemic strokes, a safe and effective adjuvant antiplatelet regimen for acute revascularization has become a subject of interest. Ticagrelor is a direct oral P2Y12 inhibitor that may achieve rapid platelet suppression than standard oral therapies. We report our experience of Ticagrelor use in revascularization of acute large arterial steno-occlusive disease, describing procedural post-procedure thrombotic events, major hemorrhages, and other clinical outcomes.. This was a single-center retrospective case series of large steno-occlusive disease requiring endovascular reperfusion with emergent adjuvant Ticagrelor, defined as 30 min of the procedure from skin puncture to closure of the arteriotomy. Major outcomes investigated were thromboembolism in the target artery, and symptomatic intracranial or extracranial major hemorrhages. Additional analyses were performed with respect to timing of the administration and use of rescue GPIIb/IIIa inhibitors if any.. 73 consecutive patients were identified, presenting with severe ischemic stroke (median NIHSS 16) of large artery origin. 67% required stent placement (45% cervical carotid, 22% intracranial artery), 9.5% angioplasty and 23% mechanical thrombectomy only. Two experienced symptomatic in-stent occlusion, and 7 experienced major hemorrhages (9.5%) including 3 fatal symptomatic intracranial hemorrhages (4.1%). Among 19 subjects (26%) who received pretreatment with Ticagrelor, there were fewer GPIIb/IIIa administration, angioplasty and stenting, without yielding benefit in functional outcome or mortality. GPIIb/IIIa was administered as rescue therapy in 45 subjects (62%), which was found associated with increased bleeding compared to patients receiving Ticagrelor only, in whom no bleeding complications were recorded (16% vs. 0%; p = 0.03).. We report our findings on Ticagrelor as an adjuvant antiplatelet therapy in ischemic stroke of large arterial origin requiring emergent revascularization. Effectiveness, safety, need for additional rescue treatment, and comparison to other commonly used oral antiplatelets should be investigated in future prospective studies.

Topics: Arterial Occlusive Diseases; Endovascular Procedures; Humans; Intracranial Hemorrhages; Ischemic Stroke; Reperfusion; Retrospective Studies; Stents; Stroke; Thrombectomy; Ticagrelor; Treatment Outcome