Experts in cardiovascular disease discuss the lack of data supporting dose adjustment of DOACs because of weight.
Jessica Kerr, PharmD, CDE: This is great discussion. One last question when we’re looking at and talking about the trials: With any of the data that came out from the trials, were there any discussions on specific weight-based recommendation for dosages?
Paul Dobesh, PharmD, FCCP, BCPS: That’s a great question. All these studies used BMIs as cutoffs. The big randomized trials, when they went back, they collected body-weight information. If you’re using claims data, there’s no way you’re going to get body weight. A lot of the real-world data have to use BMI. Even in the analysis by Costa and Coleman from the University of Connecticut, they used BMI. The randomized controlled trials did. Most of them use a cutoff of 100 kg. They went back and evaluated the patient, whether you weigh over 100 kg or less than 100 kg. I can’t remember if you were exactly 100—I think the upper half. Most of these used cutoffs of 100 kg. There might be a study or 2, and I can’t remember the specifics that might have used 120. But in those analyses it seems to be consistent safety and efficacy.
One of the things that it is somewhat interesting and that we already talked about is the subanalysis with rivaroxaban from the ROCKET AF trial. The subanalysis in patients with apixaban actually showed the bleeding benefit, which was seen in the overall study, was lost in heavier patients, which I thought was kind of interesting. Who knows if that’s a real finding or not, but statistically they lost significance in that group, and the point estimate basically came back to neutral.
Jessica Kerr, PharmD, CDE: Is it fair to say, or even correct to say, that there are no dosage-requirement changes like we would do with renal adjustments? Is there any dose adjustment for a person’s weight?
Paul Dobesh, PharmD, FCCP, BCPS: Not at this time. I don’t think we know. Would that be right? We don’t know what that would be. Maybe we have more experiences with these drugs over 10 years. The key with these drugs is that they are fixed dose. I will tell you clearly the evidence that I have seen with rivaroxaban shows that there is no need for dose adjustment. It performs, whether it’s VTE, A-fib, drug concentrations data show that it is doing what it’s supposed to do, and it doesn’t matter how big the patient is. With other DOACs that’s not as consistent. Maybe in the future there might be studying into, if you drop your anticoagulant activity by a third, what’s the representative increase that we might need for those patients to maintain adequate anticoagulant activity? That has yet to be determined.
Jessica Kerr, PharmD, CDE: Dr Johnson, when you have the consideration of using DOACs in your obese population, how often do you readily use those? How do you use them? Give us a little more. You don’t have to speak specifically on your practice—obviously, you work with some great colleagues whom you feel confident in. Just share the real-world thought processes.
Matthew Johnson, MD: I definitely think the thought process is that ideally we’re not going to base on weight adjustments. They’re not a weight-based dosing adjustment. The only real dosing adjustment is renal indications. Clinically, as we approach patients, as we get more information, especially with rivaroxaban, I think you feel a lot more comfortable using that in these patients as we start to see more analysis come through. From a clinical standpoint, we are not dose adjusting on weight-based dosing frame. That’s the beauty of the DOACs in general. As you start to talk about some of the guideline recommendations on extreme obesity or a BMI of 40, and they start to talk about possibly doing drug levels or an anticoagulant activity level that starts to flutter the beauty of the drugs themselves. When we started doing that, we started to defeat the whole purpose of coming out with the fixed-based dosing here. Clinically practitioners aren’t getting down possibly into the detail of all the obesity data, but they’re relying on the reassurance from these analyses, especially in the last year or 2.