Critical appraisal of ticagrelor in the management of acute coronary syndrome

James J Nawarskas, Stanley S SnowdenUniversity of New Mexico College of Pharmacy, Albuquerque, NM, USAAbstract: Ticagrelor is a novel P2Y12 receptor antagonist which, like clopidogrel and prasugrel, functions by blocking adenosine diphosphate-mediated platelet aggregation. However, unlike the aforementioned agents, the binding of ticagrelor to this receptor is reversible. Ticagrelor is also believed to mediate some of its beneficial effects by augmenting the effects of adenosine, which is another unique pharmacologic property of this drug. In terms of antiplatelet effect, ticagrelor is more potent than clopidogrel and produces a faster and stronger inhibition of platelet aggregation. This may also be an advantage of ticagrelor over prasugrel, but this has not been adequately studied. Due to the reversible nature of the binding of ticagrelor to the platelet receptor, ticagrelor has a relatively fast offset of effect, with platelet aggregation approaching pretreatment levels about 3 days after discontinuation of therapy. This has advantages in patients requiring invasive procedures, but also makes medication adherence very important in order to be able to maintain an effective antiplatelet effect. Ticagrelor has been shown to be clinically superior to clopidogrel when given to patients with an acute coronary syndrome, resulting in significantly lower rates of myocardial infarction and vascular death. However, ticagrelor is indicated to be administered with aspirin, and the clinical benefits of ticagrelor may be less when daily dosages of aspirin exceed 100 mg. As expected, bleeding is the most common adverse effect with ticagrelor, although it occurs at rates comparable with those seen for clopidogrel with the exception of noncoronary artery bypass graft-related major bleeding and fatal intracranial bleeds, the latter of which occurs only rarely. Dyspnea is another common adverse effect with ticagrelor, although this is usually not severe and resolves with drug discontinuation. Unlike clopidogrel, there are no known pharmacogenomic concerns with ticagrelor, and emerging data suggest ticagrelor to be effective in patients resistant to clopidogrel, although more study is needed on this topic. While preliminary data suggest ticagrelor to be cost effective when compared with generic clopidogrel, the acquisition cost of ticagrelor is not insignificant and this will likely be an issue for many health care organizations. Currently, ticagrelor is well positioned to assume an active role in the treatment of coronary artery disease due to an impressive efficacy profile and reasonable safety. Its ultimate role in therapy will continue to evolve as studies on this drug continue eg, (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin, PEGASUS) and more information hopefully becomes available on its use in clopidogrel nonresponders and relative safety and efficacy compared with prasugrel.Keywords: ticagrelor, P2Y12, adenosine receptor antagonis

P2Y12 inhibitors for acute coronary syndromes: current perspectives

James J Nawarskas,1 Cheyenne Newsome,2 Joe R Anderson,1 Bina Ahmed3 1Department of Pharmacy Practice and Pharmacy Administration, The University of New Mexico College of Pharmacy, 2Department of Pharmacy, The University of New Mexico Hospitals, 3Department of Internal Medicine, The University of New Mexico School of Medicine, The University of New Mexico, Albuquerque, NM, USA Abstract: Antiplatelet therapies are a cornerstone for the management of acute coronary syndromes (ACSs), based largely on the prominent role that platelet activation and aggregation has on the pathophysiology of the disease. Dual-antiplatelet therapy involving an oral P2Y12 inhibitor plus aspirin is now considered standard of care for treating ACS. While clopidogrel has enjoyed nearly exclusive use as the P2Y12 inhibitor of choice for many years, the more powerful P2Y12 inhibitors prasugrel and ticagrelor have recently challenged clopidogrel as the preferred antiplatelet therapy for treating ACS. Both prasugrel and ticagrelor have proven to be superior to clopidogrel in reducing cardiovascular events in large clinical trials, albeit at the risk of increased bleeding. With the availability of these newer more potent agents, tailoring P2Y12 inhibition to be more patient specific becomes an intriguing possibility. Factors such as type of ACS presentation, patient comorbidities, use of concomitant medications, platelet reactivity, genetic predisposition, and cost should all be considered. In addition to oral agents, intravenous P2Y12 inhibition with cangrelor offers the advantage of quick onset and offset of action, but its clinical role is yet to be defined. Optimal medical and mechanical treatment of ACS hinges on suppressing platelet-related pathways, and P2Y12 inhibition plays a key role. As our understanding of ACS continues to evolve, there remains much to learn with respect to optimizing the use of these powerful drugs to most effectively help achieve the best clinical outcomes. Keywords: P2Y12 inhibitors, acute coronary syndrome, ticagrelor, prasugrel, clopidogre