The possible increased incidence of pradaxa side effects of serious bleeding have become newsworthy since my post on Pradaxa in July, Pradaxa side effects especially bleeding complications have dominated the news on this new anticoagulant. I think it is hard to put these pradaxa bleeding side effects in perspective. The use of Pradaxa has been quite popular in the treatment of patients with atrial fibrillation for the treatment of stroke. In the initial study of approximately 18,000 patients that led to the FDA approval of Pradaxa the incidence of bleeding complications was fairly similar to the incidence of bleeding on warfarin therapy. Between the FDA approval of Pradaxa in October 2010 through August 2011 the FDA reports approximately 1.1 million Pradaxa prescriptions dispensed in the US and over 3 to 70,000 individual patients treated with Pradaxa from outpatient retail pharmacies. This is a lot of patients and with the known bleeding complication rates of both warfarin and Pradaxa significant number of major bleeding side effects would’ve been expected. This is been the case and the FDA is currently reviewing aftermarket use of Pradaxa using a process called The Mini-Sentinal surveillance program to see if the bleeding complication rate in newly started patients on Pradaxa is comparable to warfarin or maybe better or worse. Certainly the Pradaxa side effects of major bleeding are dramatic and can be life-threatening, just as the same as these complications with warfarin use can be. Still the benefit of stroke prevention in atrial fibrillation patients is generally felt to be enough higher than the risk of bleeding complications that anticoagulation therapy with either warfarin, Pradaxa, apixaban or one of the other anticoagulants on the market is felt to be indicated for many patients.
I’ve heard from patients and red in the news about the fact that Pradaxa cannot be reversed with vitamin K like warfarin can. I think this is a seriously flawed argument. The Pradaxa half-life is short enough that requires twice daily dosing (12-17 hours) and within about 36 hours after the last dose of Pradaxa it’s anticoagulation effect should be largely gone in patients with normal renal function. When using vitamin K as an antidote warfarin it takes a day or two for significant hepatic metabolism of the coagulation factors inhibited by warfarin and I seriously doubt if use of vitamin K leads to a reversal of the anti-coagulation in warfarin patients any faster than or even as fast as simply discontinuation of Pradaxa therapy. It’s true that in major emergencies either fresh frozen plasma or other coagulation factor products can be used as an infusion to reverse the quite neuropathy in warfarin use. Pradaxa works directly as an inhibitor of coagulation, so its anticoagulation effect should be less responsive to this type of therapy. Still I suspect that the argument that there’s no antidote for Pradaxa is less important clinically than it sounds in newsprint.
It will be interesting to see how the aftermarket evaluation of Pradaxa and the other newer anticoagulants bears out. Patients taking Pradaxa seem to certainly appreciate not needing to have frequent coagulation clinic visits to monitor their quite elation status necessary with warfarin use, and so far thankfully I’m not aware of any of my patients who have had bleeding complications from Pradaxa. I seem to see the current local cardiologists still prescribing Pradaxa fairly frequently and my expectations are that as more data comes to bear on the situation Pradaxa will be found to have a bleeding complication rate fairly similar to warfarin. Stay tuned for more updates regarding Pradaxa side effects and efficacy as they become available.