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18 protocols using ticagrelor

1

Ticagrelor Modulates Atherosclerosis in ApoE−/− Mice

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Seventy-five C57BL/6 ApoE-/- mice were purchased from Jackson Laboratory (Bar Harbor, ME, USA) and were randomly divided into five groups after 1 week of acclimation: (1) high-cholesterol diet (HCD, n = 15): 1% cholesterol and 5% lard (Alpha Biotechnologies, Wuhan, China) for 16 weeks; (2) HCD plus ticagrelor (AstraZeneca, London, UK) 25 mg/kg/d by gavage for 16 weeks (T1, n = 15); (3) HCD plus ticagrelor 50 mg/kg/d by gavage for 16 weeks (T2, n = 15); (4) HCD plus ticagrelor 100 mg/kg/d by gavage for 16 weeks (T3, n = 15); and (5) a normal diet group (ND, n = 15). The ND and HCD group received saline as control. All animals were allowed to drink water ad libitum and gained weight during the process of the study. Mice were bred and maintained in the animal center of Beijing University. All animal studies were approved by the animal study committee of Tongji Medical College of Huazhong University of Science and Technology following the principles of the experimental animal ethics.
At day 0 and at week 16, fractionated blood was collected from the caudal vein in conscious mice (0.1–0.2 ml each time) to measure blood lipids, serum TSLP levels, ATP release, platelet aggregation, and expression of TSLPR, CD62, and CD63.
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2

Carotid Doppler and Cardiac Assessment

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Ticagrelor was obtained from AstraZeneca Pharmaceutical Co., Ltd. (Cambridge, UK) with the approval no. H20171079, and atorvastatin calcium tablets were obtained from Pfizer Pharmaceuticals Limited (New York, NY, USA) with the approval no. H20051408. A Carotid doppler ultrasound (CDU) was obtained from Qisheng (Shanghai) Medical Device Co., Ltd. with the approval no. GXZJ20153541809, a 12-lead electrocardiogram (ECG) machine (model ECG-1350) was obtained from Jinan Shengrui Biotechnology Co., Ltd., and an automatic biochemical analyzer was obtained from Shandong Biobase Technological Instrument Co., Ltd. An enzyme-linked immunosorbent assay (ELISA) kit was obtained from Shanghai Jingkang Bioengineering Co., Ltd., and an enzyme-labeling instrument was obtained from Shanghai Yongchuang Bioengineering Co., Ltd.
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3

Ticagrelor versus Clopidogrel in Aspirin Therapy

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The patients in the ticagrelor group received 300 mg of aspirin (Bayer, Germany) and 180 mg of ticagrelor (AstraZeneca, UK) once daily, and the patients in the clopidogrel group received 300 mg of aspirin and 600 mg of clopidogrel (Sanofi, France) once daily.
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4

Postoperative Antiplatelet Therapy

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Patients received routine medical and nursing care from community-based physicians and cardiologists after discharge from the hospital. Conventional treatment consisted of the postoperative administration of 100 mg aspirin (Bayer Leverkusen, Germany) once daily for long-term maintenance. Oral ticagrelor (AstraZeneca, Wilmington, DE) 90 mg twice daily was prescribed for one year. Other medications (statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, and β-receptor blockers) were given as needed according to the patient’s condition. Routine care comprised post-PCI patient health education and medication management information provided by ward nurses prior to discharge, and regular follow-ups. The routine medical care was in accordance with the guidelines for cardiovascular rehabilitation and secondary prevention in China 2018 simplified edition23 .
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5

Antiplatelet Agents Modulate ConA-Induced Immune Hepatitis

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A single dose of ConA (Sigma-Aldrich, St. Louis, MO) was dissolved in normal saline solution at a concentration of 10 mg/ml. At the age of 8-10 weeks, mice were intravenously injected with ConA at 7.5, 10, 12.5, 15 or 20 mg/kg body weight, through the tail vein and their survival rate was monitored continuously for 7 days. The ConA dose of 12.5 mg/kg body weight injected intravenously was selected to induce immune hepatitis in mice. Clopidogrel (Sanofi Clir SNC, France) (7.5, 15, 30 mg/kg body weight) or ticagrelor (AstraZeneca AB, Sweden) (15, 30, 60 mg/kg body weight) was administered orally once daily for 7 days before ConA treatment. Clopidogrel (15 mg/kg body weight) or ticagrelor (15 mg/kg body weight) was administered orally once after ConA treatment 30 min, 1 hr or 12 hr. A 0.9% saline solution was used as vehicle.
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6

Intracranial Aneurysm Treatment with WEB

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Procedures were performed under general anesthesia on a biplane angiographic system (Axiom Artis, Siemens Biplane and Allura Clarity, Philips Healthcare). Since 2013, all patients treated with WEB (with or without stent) received premedication with double antiplatelet treatment (DAPT). Two protocols were used successively: aspirin and clopidogrel (Sanofi-Aventis, Gentilly, France) for 5 days until April 2015, followed by aspirin and ticagrelor (AstraZeneca, Courbevoie, France) for 2 days. The change of DAPT protocol was prompted by the high rate of clopidogrel resistance. In the event of stent placement, this treatment continued for 3 months; thereafter, clopidogrel or ticagrelor were stopped and aspirin continued for at least 12 months post-procedure date. Antiplatelet activity testing was not performed.
Post-procedure MRI including diffusion-weighted imaging (DWI) was performed 24 hours post-procedure. Digital subtraction angiography (DSA) was performed at 6 and 12 months.
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7

Ticagrelor Pharmacokinetics in ApoE-/- Mice

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Female apoE−/− mice with a C57BL/6 background were housed in the animal care facility at the University of Heidelberg in a temperature-controlled room on a 12-hour light cycle. The mice were randomized, at 8 weeks of age, to receive standard chow supplemented with ticagrelor (AstraZeneca, Gothenburg, Sweden), 0.05% (90 mg/kg/day) (n=3) or 0.1% (180 mg/kg/day) (n=3). Blood samples were collected on several days at different times of the day. Plasma was prepared within 30 minutes of blood sampling by centrifugation at 1,500× g for 10 minutes at 4°C. The plasma was transferred into tubes and stored at −20°C within 1 hour of sample collection. Plasma concentration of ticagrelor was determined by protein precipitation and liquid chromatography mass spectrometry as described previously.18
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8

Ticagrelor Versus Placebo in Patients

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Patients were randomly assigned 1:1 to receive either ticagrelor 90 mg twice daily or matched placebo tablets (AstraZeneca, Cambridge, United Kingdom). Randomization was performed by using a Web-based system that ensured allocation concealment, with treatment allocation incorporating minimization based on age (<65 and ≥65 years of age), sex, baseline plasma high-sensitivity troponin I concentration (≤5.1 and >5.1 ng/l), and the presence or absence of coronary 18F-fluoride uptake. A random element was included with a 1 in 10 chance of the determined treatment allocation being switched to the other treatment arm.
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9

Platelet Inhibition Assay Protocol

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Apyrase and prostaglandin E1 were purchased from Sigma-Aldrich Corporation (St. Louis, MO, USA). Thrombin was obtained from Enzyme Research Laboratories (South Bend, IN, USA). CD45 antibody was obtained from Bio-Rad (Hercules, CA, USA). Biotinylated goat anti-rat antibody was obtained from Vector (Burlingame, CA, USA). ASA was obtained from Bayer Health Care (Leverkusen, Germany), ticagrelor was obtained from AstraZeneca PLC (Shanghai, China), clopidogrel was purchased from Sanofi Winthrop Industrie (Shanghai, China), and prasugrel was purchased from Bio tool (Houston, TX, USA). Prasugrel and clopidogrel active metabolites were purchased from Shanghai Race Chemical Co., Ltd. (Shanghai, China). The Masson Stain Kit was obtained from Shanghai Yeasen Biological Technology Co., Ltd. (Shanghai, China).
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10

Atorvastatin, Dapagliflozin, and Metoprolol for STEMI

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Immediately after admission, the patients received general treatment, including ECG, blood pressure, and oxygen saturation detection, bed rest, establishment of venous channels, oxygen inhalation, and correction of water, electrolyte balance, and acid-base balance disorders. Meanwhile, atorvastatin or rosuvastatin was used for plaque stabilization in all three groups. All patients were given oral 300 mg of aspirin (Bayer Health Care Co., Ltd., National drug approval number: J20080078) and 180 mg of ticagrelor (AstraZeneca AB, National drug approval number: J20130020) and then underwent emergency PCI. After PCI, aspirin (100 mg/d) and ticagrelor (180 mg/d) were routinely taken orally. Group C was given placebo, and group B was given dapagliflozin (AstraZeneca Pharmaceuticals Co., Ltd., National drug approval number: J20170040), 10 mg/time, once a day. Group A was given dapagliflozin combined with metoprolol succinate sustained-release tablets (AstraZeneca Pharmaceuticals Co., Ltd., National Drug approval number: J20150044), dapagliflozin was given as group B, and metoprolol succinate sustained-release tablets were given orally, 11.875-47.5 mg/time, once a day. All three groups were treated continuously for 3 months.
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