Knowledge about antiplatelet drugs - ticagrelor.🩸🩸🩸

Ticagrelor is an antiplatelet drug. It is a potent P2Y12 receptor antagonist. For patients with acute coronary syndromes, ticagrelor is recommended as first-line treatment in the treatment guidelines of many countries. The following will introduce the knowledge about its use.

The mechanism of ticagrelor.

Platelet aggregation refers to the adhesion of platelets to platelets. Normally, glycoprotein IIb/IIIa (GP IIb/IIIa) receptor on the platelet membrane is not activated. It does not bind to fibrinogen. Early thrombus formation is because after GP IIb/IIIa receptor is activated and it binds to fibrinogen. Fibrinogen makes it be able to connect to adjacent platelets and causing platelets aggregation. 

GP IIb/IIIa receptor is directly inhibited by tirofiban and eptifibatide, so that fibrinogen cannot bind to it. 

Adenosine diphosphate (ADP) enters platelet through platelet P2Y12 receptor and then activating GP IIb/IIIa receptor. Ticagrelor reversibly inhibits P2Y12 receptor and the active metabolite of clopidogrel irreversibly inhibits P2Y12 receptor. These drugs prevent the P2Y12 receptor from binding to ADP. GP IIb/IIIa receptors are unable to activate and prevent platelet aggregation.

Adverse reactions to ticagrelor.

The most common side effect of ticagrelor is the risk of bleeding. It prolongs the bleeding and has no antidote. It is contraindicated in patients with active pathological bleeding or a history of intracranial hemorrhage. It should also not be enabled when a patient is undergoing emergency coronary artery bypass surgery.

In addition, it increases the concentration of adenosine in the blood. Elevated adenosine concentrations can cause other adverse effects of ticagrelor such as bradycardia and dyspnea. In addition, adenosine also promotes the synthesis of uric acid, which can lead to hyperuricemia or gout.

Difference between ticagrelor and clopidogrel.

Studies have shown that ticagrelor is more effective than clopidogrel in the first 12 months of acute coronary syndrome. However, ticagrelor has a higher incidence of side effects such as bradycardia, dyspnea, bleeding, and increased uric acid levels than clopidogrel.

Rapid antiplatelet therapy for acute coronary syndromes.

All patients without contraindications should be given aspirin immediately. The loading dose is 300 mg, followed by a long-term maintenance dose of 75 to 100 mg daily. All patients should receive a P2Y12 receptor antagonist for more than 12 months in addition to aspirin unless the patient has a high risk of bleeding or other contraindications. Among P2Y12 receptor antagonists, ticagrelor is the drug of choice. Its loading dose is 180 mg, followed by 90 mg twice a day. In patients with contraindications to ticagrelor, clopidogrel should be used. Its loading dose is 300 to 600 mg, followed by 75 mg once daily.

Oral antiplatelet therapy in stable coronary heart disease.

In patients with stable coronary heart disease without contraindications to aspirin, daily 75 to 100 mg of aspirin should be used as a long-term treatment. If the patient is intolerant to aspirin, it recommends taking a P2Y12 receptor antagonist. Ticagrelor 60 to 90 mg twice daily or clopidogrel 75 mg once daily. Aspirin combined with ticagrelor (60 mg twice a day) can be considered as a long-term treatment if the bleeding risk is not high in patients at high risk of thrombosis.

Precautions while using ticagrelor.

Food has only a small effect on ticagrelor, so it can be taken before or after meal.

If the patient cannot swallow whole ticagrelor tablet, it can be crushed and taken or given by nasogastric tube.

Since the half-life of ticagrelor is approximately 7 hours and the half-life of its active metabolite is approximately 9 hours, if a patient misses a dose, another dose is not required. One missed dose has limited effect on the antiplatelet effect.

The clinical efficacy of ticagrelor is reduced by high doses (greater than 100 mg) of aspirin. In addition, ticagrelor can cause severe and even fatal bleeding when used in combination with maintenance doses of aspirin greater than 100 mg/day. Therefore, the maintenance dose of aspirin should not exceed 100 mg, typically 75 to 100 mg per day.

The metabolism of ticagrelor is via CYP3A4. Therefore, strong CYP3A4 inducers (such as carbamazepine, phenobarbital, phenytoin, dexamethasone, rifampin, etc.) and strong CYP3A4 inhibitors (such as voriconazole, itraconazole, clarithromycin, etc.) should be avoided taking with ticagrelor. Additionally, because ticagrelor metabolism requires depletion of CYP3A4, it is a CYP3A4 inhibitor. When simvastatin or lovastatin is used in combination with ticagrelor, the dose of simvastatin and lovastatin should not exceed 40 mg.