Paul Dobesh, PharmD, FCCP, BCPS, provides a review of the available direct oral anticoagulants.
Jessica Kerr, PharmD, CDE: Dr Dobesh, this class has grown tremendously from researched practice in the last decade. It might be extremely helpful to expand further with each product, specifically in the factor Xa class from when we're looking at apixaban, rivaroxaban, edoxaban, and betrixaban. If you could talk a little bit about those, then we can move into dabigatran, the factor IIa inhibitor, shedding light on some of the similarities and differences among those agents in terms of indication, efficacy, dosage form as well as safety.
Paul Dobesh, PharmD, FCCP, BCPS: Sure, when you look at these agents, many of them have the same indications, but there are some that have a little extra, some that have a little less. It's important for us to realize the indications that these agents have because that tells you where they have been studied and successful. This is not a one-drug-fits-all type of thing for a lot of patients. Let’s talk about betrixaban, the newest one first, because it's the simplest. It has an indication for extended prophylaxis in medically ill patients. It is not indicated for preventing stroke and atrial fibrillation . It's not indicated for orthopedic surgery or VTE or anything like that. That drug has just 1 indication.
If you look at the others, apixaban, rivaroxaban, and edoxaban, all 3 of those drugs are indicated for reducing the risk of stroke and nonvalve-related defibrillation. All 3 of those drugs are indicated for the treatment of VTE, whether that be DVT or pulmonary embolism. So, all 3 of them share both of those indications. And for edoxaban, it adds those 2, basically. apixaban and rivaroxaban also have indications to reduce venous thromboembolic events in patients who undergo high-risk orthopedic surgery. So if you have a knee replacement, a hip replacement, apixaban and rivaroxaban both demonstrated safety and efficacy in those populations.
Finally with rivaroxaban, they have even more. They have indication for medically ill, extended prophylaxis, much like betrixaban. They are the only ones to also have that indication. They also have an indication in the treatment of arterial disease. No other direct oral anticoagulant has that. It’s a very low dose of the agent in that setting, 2.5 mg twice a day with low-dose aspirin. And it has been shown to prevent recurrent events in patients who have stable coronary artery disease or peripheral arterial disease. It is not used for acute, like acute coronary syndrome or anything like that, but it's for patients with stable disease.
Now, dabigatran, going to our direct thrombin inhibitor, has indications like most of the others. It's indicated to reduce the risk of stroke and AF. It's indicated to treat venous thromboembolic disease. And it's interesting, for orthopedic surgery it can be used for the prevention of thrombosis in hips, but not knees. That's kind of interesting. It's been studied in both, but it's knee study actually failed. It is indicated for hips but not knees. So, there are several different indications, and knowing the indications of the different agents, and it's also important to realize that it's not the same dose. Within these studies, you see very good efficacy and safety with the DOACs when you compare them to warfarin. There are no head-to-head studies between the DOACs, making those comparisons is very challenging and really medically inappropriate.