Platelets are small blood cells that help the body form clots to stop bleeding at the site of an injured blood vessel. When a blood vessel is damaged, platelets stick together to form a plug that seals the opening in the damaged vessel. This process is called platelet aggregation. However, excessive or unwanted platelet aggregation can cause the formation of clots inside healthy blood vessels. These clots can block blood flow and lead to serious cardiovascular conditions such as heart attack or stroke. Therefore, antiplatelet drugs are used to prevent unwanted platelet aggregation. Mechanism Of Action Ticagrelor is an oral, reversibly binding P2Y12 receptor antagonist. Platelet activation and aggregation is regulated by two platelet receptors - P2Y1 and P2Y12. The P2Y12 receptor plays a key role in amplifying platelet activation signals initiated by other agonists like thromboxane A2 and thrombin. It selectively and reversibly binds to the P2Y12 receptor to prevent ADP-induced platelet aggregation. Unlike the older P2Y12 antagonist clopidogrel, it does not require metabolic activation through the CYP450 system. This allows it to have a quicker onset and more consistent antiplatelet effect compared to clopidogrel. Clinical Trials and Studies Ticagrelor was studied in the large multicenter Platelet Inhibition and Patient Outcomes (PLATO) trial which compared it to clopidogrel in over 18,000 patients with acute coronary syndrome with or without ST-segment elevation. The primary endpoint was cardiovascular death, myocardial infarction or stroke at 12 months. Results showed it was superior to clopidogrel in reducing the primary endpoint with an absolute risk reduction of 1.9%. It also significantly reduced all-cause mortality by 16% compared to clopidogrel. Subgroup analyses showed consistent benefit across all major subgroups including age, sex, region, revascularization status etc. Side effects and Precautions Like all antiplatelet drugs, it carries a risk of bleeding due to its antiplatelet effect. In the PLATO trial, it was associated with significantly higher rates of major bleeding not related to coronary artery bypass grafting compared to clopidogrel (11.6% vs. 9.8%). Increased risk of non-coronary artery bypass graft related major bleeding was also seen in a meta-analysis. Other common side effects reported more frequently with it include dyspnea and ventricular pauses. Due to risk of bleeding, it should be used with caution in patients at high bleeding risk or with history of stroke or TIA. Patients on ticagrelor also require occasional non-invasive or invasive procedures or surgeries should be managed carefully. Standard Dosing and Practical Usage The approved dosing of ticagrelor is 90 mg twice daily orally with or without food. Treatment should be initiated with a 180 mg loading dose. It can be used for up to 12 months after acute coronary syndrome or for up to 36 months in patients with a drug-eluting stent implanted. For patients who undergo coronary artery bypass grafting, it should be discontinued at least 24 hours prior to surgery to reduce bleeding risk. Due to its reversible binding and lack of metabolism, it can be administered to patients with mild to moderate kidney or liver impairment. There is limited experience in severe impairment. Role in Clinical Guidelines It is now recommended over clopidogrel as the preferred P2Y12 inhibitor after acute coronary syndrome in major guidelines including the European Society of Cardiology and American College of Cardiology/American Heart Association guidelines. This is due to ticagrelor's consistent clinical efficacy in reducing cardiovascular events demonstrated in landmark PLATO trial as well as greater, albeit modest, potency compared to clopidogrel. It is now considered the standard of care for post-ACS antiplatelet therapy barring specific contraindications. With advances in percutaneous coronary intervention techniques and drug-eluting stents, using potent newer antiplatelet agents like it helps improve long-term outcomes in ACS patients managed with a conservative or invasive approach.
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