ticagrelor and Obesity

Body mass index (BMI) may affect the response to platelet P2Y. In a multicentre, randomized, double-blind, placebo-controlled trial, conducted in China, we randomized patients with minor stroke or TIA who carried the. Among 6412 patients, 876 were classified as obese and 5536 were classified as nonobese. Compared with clopidogrel-ASA, ticagrelor-ASA was associated with a significantly lower rate of stroke within 90 days among patients with obesity (25 [5.4%] v. 47 [11.3%]; hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.30-0.87), but not among those in the nonobese group (166 [6.0%] v. 196 [7.0%]; HR 0.84, 95% CI 0.69-1.04) The interaction of treatment and BMI group was significant (. In this secondary analysis of a randomized controlled trial involving patients with minor ischemic stroke or TIA, compared with clopidogrel-ASA, patients with obesity received more clinical benefit from ticagrelor-ASA therapy than those without obesity.. Clinicaltrials.gov, no. NCT04078737.

Topics: Aspirin; Body Mass Index; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Obesity; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

Obese patients exhibit an overall increased platelet reactivity and a reduced sensitivity to antiplatelet therapy. The aim of this study is to evaluate the platelet reactivity measured by impedance aggregometry in overweight and obese patients and chronic coronary syndrome (CCS) that were treated with dual antiplatelet therapy (DAPT).. Platelet aggregation was assessed by impedance aggregometry in patients with CCS receiving DAPT (aspirin plus clopidogrel). We compared the platelet reactivity in patients with a normal weight versus overweight or obese patients. Furthermore, the correlation between the body mass index (BMI) and adenosine diphosphate- (ADP-) or thrombin receptor-activating peptide- (TRAP-) dependent platelet aggregation was analyzed.. 64 patients were included in the study of which 35.9% were patients with normal weight. A higher ADP- and TRAP-dependent platelet reactivity was observed in overweight and obese patients (ADP: median 27 units (U) [IQR 13-39.5] vs. 7 U [6-15], p < 0.001 and TRAP: 97 U [73-118.5] vs. 85 U [36-103], p = 0.035). Significant positive correlations were observed between agonist-induced platelet reactivity and BMI.. Despite the use of DAPT, a higher platelet reactivity was found in overweight and obese patients with CCS. If these patients will benefit from treatment with more potent platelet inhibitors, it needs to be evaluated in future clinical trials.

Topics: Adenosine; Adenosine Diphosphate; Aspirin; Blood Platelets; Clopidogrel; Humans; Obesity; Overweight; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Ticagrelor; Ticlopidine

Ticagrelor inhibits the equilibrative-nucleoside-transporter-1 and thereby, adenosine cell re-uptake. Ticagrelor limits infarct size (IS) in non-diabetic rats and the effect is adenosine-dependent. Statins, via ecto-5'-nucleotidase activation, also increase adenosine levels and limit IS.. Ticagrelor and rosuvastatin have additive effects on myocardial adenosine levels, and therefore, on IS and post-reperfusion activation of the NLRP3-inflammasome.. Diabetic ZDF rats received via oral gavage; water (control), ticagrelor (150 mg/kg/d), prasugrel (7.5 mg/kg/d), rosuvastatin (5 mg/kg/d), ticagrelor + rosuvastatin and prasugrel + rosuvastatin for 3d. On day 4, rats underwent 30 min coronary artery occlusion and 24 h of reperfusion. Two additional groups received, ticagrelor + rosuvastatin or water in combination with CGS15943 (CGS, an adenosine receptor antagonist, 10 mg/kg i.p. 1 h before ischemia).. Both ticagrelor and rosuvastatin increased myocardial adenosine levels with an additive effect of the combination whereas prasugrel had no effect. Similarly, both ticagrelor and rosuvastatin significantly reduced IS with an additive effect of the combination whereas prasugrel had no effect. The effect on IS was adenosine dependent as CGS15943 reversed the effect of ticagrelor + rosuvastatin. The ischemia-reperfusion injury increased myocardial mRNA levels of NLRP3, ASC, IL-1β and IL-6. Ticagrelor and rosuvastatin, but not prasugrel, significantly decreased these pro-inflammatory mediators with a trend to an additive effect of the combination. The combination also increased the levels of anti-inflammatory 15-epilipoxin A. Ticagrelor and rosuvastatin when given in combination have an additive effect on local myocardial adenosine levels in the setting of ischemia reperfusion. This translates into an additive cardioprotective effect mediated by adenosine-induced effects including downregulation of pro- but upregulation of anti-inflammatory mediators.

Topics: Adenosine; Animals; Apoptosis Regulatory Proteins; CARD Signaling Adaptor Proteins; Cardiotonic Agents; Cyclooxygenase 2; Diabetes Mellitus, Experimental; Drug Synergism; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-1beta; Interleukin-6; Lipoxins; Male; Myocardial Reperfusion Injury; Myocardium; NLR Family, Pyrin Domain-Containing 3 Protein; Obesity; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Rats, Zucker; RNA, Messenger; Rosuvastatin Calcium; Ticagrelor