In patients who receive monitoring for P2Y12 inhibitors with the VerifyNow assay, interpretation of results can be tricky. Since the assay evaluates platelet reactivity, lower PRU values indicate more platelet inhibition (i.e., an increased risk of bleeding), whereas higher PRU values indicate less platelet inhibition (i.e., less risk of bleeding and possible risk of thrombotic events). As always, it is important to be mindful of how to interpret results whenever monitoring patients for safety and efficacy of their antithrombotic therapies.

Although many medications require an overlapping period to ensure a smooth transition, this is not the case when transitioning from cangrelor to clopidogrel or prasugrel. Due to the properties of these different medications, the activity of clopidogrel or prasugrel will actually be blocked if administered during cangrelor infusion, and the patient will not receive the effect of the drug until the next dose is given. It is important to ensure that loading doses of clopidogrel and prasugrel are not given until immediately after the cangrelor infusion is stopped in order to have the most benefit.

Special populations, such as patients who are pregnant, morbidly obese, severely malnourished or underweight, and those with organ failure (e.g., acute or chronic kidney or liver disease) may respond differently to medications than those from the normal population and often are excluded from initial trials. Differences in pharmacokinetic parameters such as absorption, distribution, metabolism, and excretion can vary significantly in these patients, and medications should be used cautiously and based on best evidence. When possible, it is useful to use therapeutic drug monitoring to ensure both efficacy and safety of high-risk medications.

Classes of antithrombotics each work in distinct ways to prevent thrombosis. When utilizing combination therapy, ensure that medications from different classes are being used together synergistically, instead of using multiple agents from the same class that work in the same way. Additionally, the more agents that are being used simultaneously (e.g., triple therapy), the more the risk of bleeding. It is important to minimize the duration of using more than two agents to reduce the risk of bleeding, whenever possible.

In the ISAR-REACT 5 trial published in 2019, authors evaluated the use of ticagrelor versus prasugrel in patients with ACS who were planned to receive invasive evaluation. Despite limitations to the study, the authors concluded that in patients with ACS with or without ST-segment elevation, prasugrel was superior to ticagrelor in this population of approximately 4,000 patients. This was supported by a lower incidence of death, MI, or stroke in the prasugrel group with a similar incidence of bleeding [60].

The CHANCE and POINT trials were two independent multicenter randomized controlled trials that showed the benefit of short-term dual antiplatelet therapy to prevent recurrent ischemic stroke in patients with minor stroke or high-risk TIA. The CHANCE trial evaluated patients who received aspirin plus clopidogrel for 21 days (followed by aspirin monotherapy) versus aspirin monotherapy for minor stroke or TIA in China. The POINT trial evaluated patients who received aspirin plus clopidogrel for 90 days versus aspirin monotherapy for minor stroke or TIA in North America, Europe, Australia, and New Zealand. In both trials, DAPT resulted in fewer ischemic events and overall benefit, though bleeding rates were higher [65,66].

In order to meet the Joint Commission standardized performance measures for comprehensive stroke centers, all patients with acute ischemic stroke must receive antithrombotic therapy by the end of hospital day two. For this reason, it is imperative that patients receive their antithrombotic (most often aspirin) as early as possible, once cleared to do so, in order to meet metrics and ensure good patient outcomes. This will typically be 24 hours after thrombolytics (e.g., alteplase or tenecteplase) or sooner in patients who are treated more conservatively.