ticagrelor and Diabetic-Angiopathies

Topics: Absorbable Implants; Acute Coronary Syndrome; Adenosine; Aftercare; Aged, 80 and over; Cardiac Imaging Techniques; Coronary Angiography; Coronary Artery Bypass; Coronary Disease; Diabetic Angiopathies; Drug Therapy, Combination; Fibrinolytic Agents; Fractional Flow Reserve, Myocardial; Graft Occlusion, Vascular; Humans; Out-of-Hospital Cardiac Arrest; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Prosthesis Design; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; ST Elevation Myocardial Infarction; Stents; Thrombectomy; Ticagrelor; Time-to-Treatment; Tissue Scaffolds

Lower extremity arterial disease (LEAD) occurs more common in patients with diabetes than without diabetes. Microvascular complications of diabetes contribute to higher rates of adverse limb events in patients with LEAD. Blood flow in the macrocirculation and microcirculation is reduced with increasing low-shear and high-shear blood viscosity. We hypothesize that the adenosine enhancing properties of ticagrelor will reduce low-shear blood viscosity and improve microcirculatory flow in the dorsum of the feet of patients with type 2 diabetes. Ticagrelor is a P2Y12 receptor antagonist with evidence of cardiovascular event reduction in patients with acute coronary syndromes and those with a previous myocardial infarction. In a large multicenter trial of patients with symptomatic LEAD and a history of limb revascularization, ticagrelor was no more effective than clopidogrel in reducing cardiovascular disease events; however, this trial was not designed to investigate microvascular complications of diabetes.. Hema-kinesis will evaluate whether ticagrelor monotherapy or ticagrelor combined with aspirin as compared with aspirin monotherapy can reduce blood viscosity-dependent blood flow in the feet of type 2 diabetes patients with LEAD. Eligible study participants will be randomized into a three-arm double-dummy crossover trial design. All subjects will have baseline blood viscosity measurements and determinations of microvascular flow using laser Doppler flowmetry. If the results of Hema-kinesis are positive, ticagrelor should be considered as treatment to reduce microvascular complications of LEAD in patients with type 2 diabetes.

Topics: Aspirin; Blood Flow Velocity; Blood Viscosity; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Drug Therapy, Combination; Humans; Laser-Doppler Flowmetry; Lower Extremity; Microcirculation; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Regional Blood Flow; Ticagrelor; Time Factors; Treatment Outcome

patients with diabetes mellitus (DM) have high platelet reactivity and are at increased risk of ischaemic events and bleeding post-acute coronary syndromes (ACS). In the PLATelet inhibition and patient Outcomes (PLATO) trial, ticagrelor reduced the primary composite endpoint of cardiovascular death, myocardial infarction, or stroke, but with similar rates of major bleeding compared with clopidogrel. We aimed to investigate the outcome with ticagrelor vs. clopidogrel in patients with DM or poor glycaemic control.. we analysed patients with pre-existing DM (n = 4662), including 1036 patients on insulin, those without DM (n = 13 951), and subgroups based on admission levels of haemoglobin A1c (HbA1c; n = 15 150). In patients with DM, the reduction in the primary composite endpoint (HR: 0.88, 95% CI: 0.76-1.03), all-cause mortality (HR: 0.82, 95% CI: 0.66-1.01), and stent thrombosis (HR: 0.65, 95% CI: 0.36-1.17) with no increase in major bleeding (HR: 0.95, 95% CI: 0.81-1.12) with ticagrelor was consistent with the overall cohort and without significant diabetes status-by-treatment interactions. There was no heterogeneity between patients with or without ongoing insulin treatment. ticagrelor reduced the primary endpoint, all-cause mortality, and stent thrombosis in patients with HbA1c above the median (HR: 0.80, 95% CI: 0.70-0.91; HR: 0.78, 95% CI: 0.65-0.93; and HR: 0.62, 95% CI: 0.39-1.00, respectively) with similar bleeding rates (HR: 0.98, 95% CI: 0.86-1.12).. ticagrelor, when compared with clopidogrel, reduced ischaemic events in ACS patients irrespective of diabetic status and glycaemic control, without an increase in major bleeding events.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Blood Glucose; Clopidogrel; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glycated Hemoglobin; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Ticagrelor; Ticlopidine; Treatment Outcome

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Diabetic Angiopathies; Humans; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine