Ticagrelor is an oral antiplatelet drug belonging to the class of P2Y12 platelet inhibitors. It works by selectively and reversibly binding to the P2Y12 receptor on platelets, preventing the activation and aggregation of platelets. It was developed by AstraZeneca as an alternative to Clopidogrel for the prevention of atherothrombotic events in patients with acute coronary syndromes and those undergoing percutaneous coronary intervention (PCI).
Mechanism of Action
The mechanism of action of Ticagrelor involves the reversible binding to the adenosine diphosphate (ADP) receptors P2Y12 on platelet membranes. When platelets are damaged at sites of vascular injury, ADP is released which stimulates more platelets to adhere and aggregate, leading to thrombus formation. Ticagrelor selectively and reversibly binds to the P2Y12 receptors, preventing ADP from activating and aggregating platelets. This results in reduced platelet reactivity and inhibition of platelet aggregation. Unlike Clopidogrel which is a prodrug requiring metabolic activation, It does not require bioactivation and binds more quickly and with greater potency and reversibility to the P2Y12 receptor.
Clinical Trials and Efficacy
The PLATO trial was a large phase III, multicenter, randomized controlled trial which compared it against Clopidogrel in 18,624 patients with acute coronary syndromes. The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction or stroke at 12 months. The trial demonstrated that it resulted in a 16% relative risk reduction in the primary composite endpoint compared to Clopidogrel (9.8% vs. 11.7%, p<0.001). It also significantly reduced the rate of total mortality compared to Clopidogrel (4.5% vs. 5.9%, p=0.001). There was no significant difference in major bleeds between the two groups.
Further Analyses from PLATO Trial
Some additional findings and subgroup analyses from the PLATO trial include:
- Ticagrelor was equally effective in reducing ischemic events compared to Clopidogrel, irrespective of whether patients underwent an invasive or conservative treatment strategy.
- The benefit of it over Clopidogrel was consistent across various prespecified subgroups based on age, gender, region, type of ACS, diabetes status, prior MI/PCI/CABG etc.
- Ticagrelor was shown to significantly reduce stent thrombosis by more than 50% compared to Clopidogrel in patients undergoing PCI.
- Patients receiving it had lower rates of stent thrombosis at 1 year compared to Clopidogrel, regardless of the type of stent implanted - bare metal or drug-eluting.
Dosing and Pharmacology
The recommended dose of it is 90 mg twice daily, with or without food. Compared to Clopidogrel which requires hepatic transformation, it is directly active and achieves maximum levels within 1-3 hours of administration without need for hepatic metabolism. The mean elimination half-life of it is 7-11 hours, allowing it to be dosed twice daily. Ticagrelor and its active metabolite are mainly metabolized by CYP3A4 and do not have significant interactions with cytochrome P450 enzyme inhibitors.
Safety Profile and Bleeding Risks
In the PLATO trial, major bleeding events defined by TIMI criteria were similar between Ticagrelor and Clopidogrel treated groups (11.6% vs. 11.2%). However, it was associated with a higher risk of non-coronary artery bypass graft (CABG)-related major bleeding (4.5% vs. 3.8%, p=0.03) and non-CABG related minor bleeding (21.6% vs. 19.9%, p=0.001). Patients on Ticagrelor also experienced higher rates of dyspnea which was mostly mild to moderate in severity. Rare but serious adverse effects include hyperuricemia, bradyarrhythmias and ventricular pauses. Caution is required in patients at high risk of bleeding or on concomitant anticoagulants.
Place in Therapy and Guidelines
Based on the results of the PLATO trial, international cardiovascular guidelines have included it as a first-line treatment option along with Prasugrel and Clopidogrel for the prevention of atherothrombotic events in patients with acute coronary syndromes and those undergoing PCI. It is preferable to Clopidogrel in patients with STEMI, those scheduled to undergo primary PCI, as well as in patients with prior history of MI, stent thrombosis or multiple lesions. It provides a useful alternative to Prasugrel owing to its more favorable safety profile in terms of bleeding risk. Overall, Ticagrelor has emerged as an established oral antiplatelet with proven efficacy in reducing ischemic outcomes post ACS and PCI.
Choose preferred language for better understanding-
About Author-
Ravina Pandya, Content Writer, has a strong foothold in the market research industry. She specializes in writing well-researched articles from different industries, including food and beverages, information and technology, healthcare, chemical and materials, etc. With an MBA in E-commerce, she has an expertise in SEO-optimized content that resonates with industry professionals. (https://www.linkedin.com/in/ravina-pandya-1a3984191)
Comments
0 comment