Atrial fibrillation Dabigatran/Rivaroxaban/Apixaban Health Care Health Care Reform

A letter to the CEO of Boerhinger Ingelheim–on Pradaxa

I remember in high school, as an assignment, I wrote a letter to a prominent business person.  I will try it again. In 2010, this would be an e-letter.

To: J Martin Carroll
CEO of Boehringer Ingelheim Corporation: The makers of the recently-released exciting new oral blood-thinner, dabigatran (Pradaxa).

Dear Sir,

To start off on a positive note, a hearty congratulations is in order. Developing a safe and effective replacement for warfarin (Coumadin) is a remarkable achievement. Simply awesome. Cheers. “H/t” and all that.  (Ed note: Presently, dabigatran is FDA-approved only for non-valvular AF.)

But before the celebration progresses much further, I wish to offer-up an idea for making your potential blockbuster into a bona fide blockbuster, in the real-world of American medicine.

My suggestion is that Boehringer Ingelheim lower the price of dabigatran!   Ridiculously low, not 250+/month, that’s not that low–how about 40-50/month? Surely, you have heard this plea before, and undoubtedly there were intense strategy sessions on how to price the drug for maximal profit. 

But sir, I have five reasons why this benevolent strategy might work:

First, do it because your company’s motto is “Value through Innovation.” 

Now, I realize you might refer readers to the recent Annals of Internal Medicine paper which suggested—via mind-boggling statistics—that dabigatran “could” be the most cost effective strategy for stroke prevention in AF.  The problem with that study is that even if those mathematical models are correct (and they depend greatly on pricing), the cost savings is to the ‘healthcare system,’ not to the individual patient at the pharmacy counter with a credit card.  Remember, stroke prevention is only one facet of AF therapy; most AF patients are on a few other medicines as well. (And they have monthly cable TV and iPhone bills to pay.)

Second, although your advisers may not have told you this very forcefully, there are many patients on long-term warfarin who do great. They eat a stable diet, don’t take new drugs without checking first, and don’t mind a trip to the warfarin “finger-stick” clinic once a month. They might switch to dabigatran if it were cheap, but not so much at 300/month.

To this, you might respond that dabigatran was proven more effective and safer than warfarin in the RE-LY trial.  This is true, but what if a patient asked me this, 

“Hey Doc, I looked at RE-LY too. You saw that the warfarin-treated group was only in therapeutic [blood-thinning] range 65% of the time. I have been in range for years…so do you think dabigatran is still better for me?”

>>Makes one think of this dreamy trial: What if dabigatran (or any new oral blood-thinner) were compared head-to-head against a cohort of well-educated motivated warfarin-treated patients who were equipped with an INR home-monitoring device which facilitated staying in ideal blood-thinning range all the time? <<

Third, to a business novice, a lower price makes sense because what you lose in margin, you would gain in volume—and in warfarin-replacement the volume would be a lot larger at 50/month than 300/month.  Since you know this angle better than me, let’s move on.

Fourth, building the largest possible volume of patients on dabigatran is time sensitive. There are formidable competitors on the horizon, and the likely next one is once daily—Rivaroxaban. BI has a head-start, but as I see it, the more brand loyalty you accrue the larger the hurdle for upcoming competitors.  

Fifth, it would be a really cool thing to do, for humanity. Think of all the goodwill BI would accumulate. And it is well known that goodwill is good for the heart.  I see that that your company wins a number of “best-places” to work awards; so you all seem to get the goodwill thing.


John Mandrola, MD

5 replies on “A letter to the CEO of Boerhinger Ingelheim–on Pradaxa”

Hey John,

Coincidentally, my brother-in-law works for Boerhinger Ingleheim in Connecticut. I will forward your post to him.

Sammy (the Bull).


Historically, even before my time, one of the most common causes of AF was valvular heart disease, specifically rheumatic mitral stenosis. The atria became huge–like a stream that is dammed would–and the propensity for clots was huge. Nowadays, in the developed world, rheumatic heart disease is very uncommon.

Although mitral stenosis is rare, valvular heart disease in general is still common. Bad heart valves–be it leaky or stenotic–often lead to dilated atria which in turn predispose to clot formation and hence the risk of stroke. These patients clearly benefit from warfarin, and thus were excluded from recent trials of AF blood-thinning drugs, which include only patients without valvular heart disease–non-valvular AF.


Thanks for that.


Thanks, John.

1. Is there also a tricuspid stenosis disease? If one valve is bad (leaky or stenotic as you mentioned above), does it cause dilation in both atria, or just the atrium on the side of the bad valve?

2. You mentioned the RE-LY trial in previous post, I have some questions about it as I don't have access to the full article. What is the warfarin dose they use in the trial to bring the patients to therapeutic INR? I ask because most AF patients have the same therapeutic INR range; however, the range of their warfarin dose (at therapeutic INR) can be quite broad. It varies from one patient to another, making it hard to compare warfarin to dabigatran in term of bleeding because patients on higher dose of warfarin would have higher risk of bleeding than those on lower dose. I try to understand how they compared one or two doses of dabigatran with a broad range of warfarin dose in term of major bleeding (not in term of primary outcome, stroke prevention). Even in one patient, warfarin dose can fluctuate from week to week due to the patient's diet, other medications, co-morbidities, etc… How do they control all of these factors in the RE-LY study? Do you think they did a good job?



Mitral valve disease can cause both RA and LA dilation. TC disease causes primarily RA dilation.

Your warfarin question is an important one. The warfarin dose may vary, both inter-patient and intra-patient. But the ultimate goal is the blood thinning effect, measured by the INR. The INR is standardized, so off warfarin–with a normal liver–one has an INR of 1.0. The INR goal that is proven effective is 2.0-3.0. For example, your INR of 2.5 is equal to mine at 2.5. Our blood is equally thin, regardless of the dose of warfarin. You might be taking 2 mg/day and I 10mg/day; if the INR is equal than we are the same thinness. This is one of the challenges of warfarin: keeping people in "therapeutic" range correlates with warfarin efficacy and safety. In Re_LY the time in range was only 65%. That's as good as any trial, and surely better than real-life.


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