Prasugrel…The New Kid on the Block!
In July 2009, the FDA approved the drug prasugrel (Effient) in the treatment of acute coronary syndrome patients who had planned percutaneous coronary intervention. Prasugrel, in clinical trials, has been associated with a decrease in ischemic events (including stent thrombosis), but also an increase in the risk of bleeding, including fatal bleeding.1 One study showed that when compared to clopidogrel (Plavix), prasugrel had greater platelet inhibition. This study looked at patients receiving 60 mg prasugrel compared to clopidogrel 600 mg po as a loading dose, and also on maintenance doses of prasugrel 10 mg versus clopidogrel 150 mg daily.2 Due to the increased bleeding shown in clinical trials, prasugrel comes with a contraindication, or black box label, if the patient has a history of stroke and transient ischemic attack (TIA), if the patient is >75 years of age and if the patient is < 60 kg. Some thought is being given to decreasing the dose of prasugrel to 5 mg for patients weighing less than 60 kg and patients older than 75. This, however, has not been studied in clinical trials.
My facility has started to use prasugrel. However, there does not seem to be any standard for when it is used or on what type of patients it is used. Some of our MDs check a P2Y12 assay, and if the inhibition is less than 50%, they change the patient from clopidogrel to prasugrel. When making this switch, some MDs give a loading dose of 60 mg, then 10 mg po daily; others do not load and just start the patient on the daily dose of 10 mg.
P2Y12 levels are not consistently rechecked once the patient has been switched from clopidogrel to prasugrel. Prasugrel is more efficient in inhibiting ADP receptors because it is more efficiently metabolized. More active metabolite is delivered to the platelet, thus preventing platelet activation to a greater extent than clopidogrel, at current doses.3 In my experience so far, there have been two patients who had 0% platelet inhibition on clopidogrel and then, when switched to prasugrel, they also had 0% inhibition. One of these patients had prasugrel dose increased to 20 mg daily and the P2Y12 assay showed a platelet inhibition of 43%.
Some thoughts that come to mind when using these antiplatelet drugs are:
1. Should we be checking P2Y12 levels on all patients on clopidogrel? To be honest, I am surprised at the number of patients whose levels come back 0% or sub-therapeutic — it’s more than I would have thought.
2. Should we be rechecking P2Y12 levels once the patient is switched to prasugrel? Although in the trials almost everyone on prasugrel had therapeutic inhibition levels, we have had, as I noted, two patients with no platelet inhibition on prasugrel.
3. Should we develop some guidelines for which patients should be placed on prasugrel versus clopidogrel?
4. One reason I looked forward to the release of a new antiplatelet drug was a hope that the new medication would be less expensive than clopidogrel. However, this is not the case. Prasugrel actually costs more than clopidogrel ($5.45/day versus $4.62/day. This is the net wholesale price as of August 2009).4 These antiplatelet drugs are a huge expense for our patients, especially Medicare patients, who have limited prescription drug benefits.
Of course, now there is a new player in the antiplatelet arena: ticagrelor. Apparently, it is doing well in European trials. We will just have to wait and see how it does in the U.S.
1. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007 Nov 15;357(20):2001-2015.
2. Wiviott SD, Trenk D, Frelinger AL, et al. Prasugrel compared with high loading- and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention: the Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial Infarction 44 trial. Circulation 2007 Dec 18;116(25):2923-2932.
3. Bhatt DL. Prasugrel in clinical practice. N Engl J Med 2009 Sep 3;361(10):940-942.
4. Cardiovascular Business. Conference News. TCT: Prasugrel costs hospitals less than clopidogrel, due to less repeat PCI. Available online at http://tinyurl.com/prasugrelTCT. Accessed February 9, 2010.