Pradaxa versus Xarelto: An e-mail exchange between a cardiologist and an ER doctor

My friend Bill is an ER doctor and a bike racer. He’s like me in that he has rediscovered the beauty of being a learner. His most recent area of inquiry is the blood clotting cascade and the use of reversal agents for the novel new blood thinners, (dabigatran, rivaroxaban and the soon to be released apixaban.)

I have been exchanging emails with Bill and two other prominent ER doctors, Robert Orman from ERCast and Dr Amal Mattu.

Here’s what Rob wrote to my friend Bill:

Hi William,

Ironically, John Mandrola is exactly the guy I would ask about this question. I am still trying to wrap my head around Pradaxa and haven’t seen any patients on Xarelto. For some of the reasons you suggest in your email, as well as the need for BID dosing, cardiologists I’ve spoken with think Pradaxa may very well be pushed aside by once daily agents like Xarelto. I’d be curious to hear what you and John have been debating about this.

I thought that I would share my response:

Hi All,

My dear friend Bill and I don’t really debate. Rather, we are struggling to best understand the role of these new blood thinners. We strive to mesh what the mega-trials tell us with what we see in the real world. That’s tough b/c our experience with warfarin is so long, and with these new agents, so short.

We both understand the benefits and risks of the drugs, but our perceptions are colored by our differing vantage points. As an ER doc and bike racer, Bill’s natural tendency is to focus on which drug can be best reversed in the event of a serious bleed. He sees bleeding a lot more than I do. I, on the other hand, am charged with protecting AF patients from stroke. I don’t see as many bleeds; I see thousands of people with AF and have to counsel them on how much risk reduction can be had, and at what cost–in dollars, convenience and bleeding risk.

Bill likes the xA inhibitors (rivaroxaban and apixaban) as they seem more easily reversed.

The problem comes when the mega-trials were analyzed more closely, the researchers found that neither rivaroxaban nor apixaban reduced ischemic (clot-related) strokes, whereas dabigatran did. Sure, each of the 3 drugs lowered OVERALL strokes, but only dabigatran did it by reducing BOTH ischemic & hemorrhagic strokes. This data point has been widely interpreted as evidence that dabigatran is the superior stroke-preventing blood thinner for AF.

Obviously, for the patient with AF, it doesn’t really matter what causes their paralysis or speech impediment; it just matters that they don’t have it in the first place. Carrying this line of reasoning further, I keep having this thought: Since in reality most patients with spontaneous brain bleeds–on any blood thinner–do poorly, isn’t it better to pick the strategy that best prevents the bleed in the first place, rather than trying to salvage marginal brain functioning after the fact with reversal agents?

For elderly trauma victims, the decision harkens back to the age-old conundrum–frailty versus stroke prevention. Surely we can all agree that if a patient is too fragile for warfarin, they are also not appropriate candidates for these drugs.

If you like learning, the new thinners are featured prominently in this advanced class: clinical-decision making 401.

JMM

References:

1.) RE-LY trial of dabigatran for AF

2.) Rocket AF trial of rivaroxaban in AF

3.) Apixaban in patients with AF;