November 4th, 2013

Should Plasma Levels of Dabigatran Guide How We Dose the Drug?

CardioExchange’s John Ryan interviews Stuart J. Connolly about his research group’s analysis of data from the manufacturer-funded RE-LY trial. The study, published in JACC, showed that the risk for ischemic events was inversely related to trough plasma concentrations of dabigatran and that the risk for major bleeding increased with dabigatran exposure.

Ryan: Your study convincingly shows the relationship between dabigatran plasma-concentration levels and risk-benefit for patients with atrial fibrillation. Should we be dosing according to those levels?

Connolly: The relationship between plasma concentration and outcomes is most convincing for bleeding. There is some reason to consider that measuring a trough plasma concentration after starting therapy would be useful in reducing bleeding risk, perhaps with a target concentration <250 ng/mL. However, this has not been demonstrated in a prospective study. We currently have no clinically available way to measure the levels. A prospective trial would be best.

Ryan: You find that many factors predicted levels. Do they reflect who was taking the medication regularly or differences in patient factors?
Connolly: Quite a lot of variation in plasma concentration is unexplained, although we know that renal function is very predictive of concentrations. A few other factors, such as concomitant medication, also have some effect on levels.

Ryan: Should we be using an algorithm in the dosing?
Connolly: An algorithm would mostly depend on renal function and would have to be validated. As you may know, we did use an algorithm in the RE-ALIGN study in valve patients, to get a more appropriate dose. Unfortunately, dabigatran did not work in those patients, so we could not really validate the algorithm.


Given the findings from Dr. Connolly and his colleagues, do you think a validated algorithm for dabigatran dosing is likely to be developed? Would you use one if it were available?

3 Responses to “Should Plasma Levels of Dabigatran Guide How We Dose the Drug?”

  1. So the advantage of dabigatran over warfarin is that you do not need to follow an INR. Do this study indicate that we should be following levels?

  2. Siqin Ye, MD says:

    I wonder how much dabigatran levels fluctuate over time, depending on temporal changes in other patient factors (such as renal function). Given the primary findings of RELY and presumably previous pharmcokinetic studies, I imagine the fluctuations are still mostly within the therapeutic range, with the exception of specific scenarios such as immediately post-op.

    If there is not a lot of fluctuations, one intriguing possibility of measuring dabigtran levels would be using it to investigate personalized dosing– measure level at time of initiation and calculate the “best” maintenance dose for each patient. Another immediate use for measuring dabigatran level would be to identify patients who are non-adherent, which has been pointed out as an issue for switching from warfarin from dabigatran.

  3. Maarten Vasbinder, MD says:

    So better go back to warfarin. It will save billions and we have a huge experience, anti-dote included.