This morning I am told, “Dr Mandrola, there are two ladies from this company, Boehinger Ingelheim, who need to to give you a secret, sealed envelope.”
I wonder whether the department of Health and Human Services knows about this exciting new potential warfarin substitute. Surely they do, as replacing the ubiquitous blood thinner warfarin with a newer, non-generic drug will cost millions.
If HHS could talk with the RE-LY investigators, would the phone conversation sound something like thisâ€¦
RE-LY Investigators: “Yes.”
Ms Sebelius: “We have some questions about your new drug, dabigatran.”
RE-LY Investigators: “Yes, what are the questions?”
Ms Sebelius: “Atrial fibrillation is the most common cardiac diagnosis. It affects millions, and is increasingly expensive to treat. AF’s primary complication is stroke. Warfarin is the present standard of care, but I understand dabigatran is an exciting new drug used to prevent strokes in patients with AF.”
RE-LY Investigators: “Yes, you are correct, the question?”
Ms Sebelius: “Is it true that in your randomized prospective trial of 18,000 patients, dabigatran, when compared to warfarin, was found to be both superior in stroke prevention and associated with less bleeding risk. It was supposed to be a non-inferiority trial, but as it turned out, dabigatran looked to be superior.”
RE-LY Investigators: “Yes, this is true.”
Ms Sebelius: “I also understand that dabigatran has no significant drug-drug, or drug-dietary interactions, and there is no need to check the INR.”
RE-LY Investigators: “Yes, this is true as well. We are really excited about this major therapeutic advance in stroke prevention.”
Ms Sebelius: “There is a problem.”
RE-LY Investigators: “A problem?”
Ms Sebelius: “Yes, you are aware that our new healthcare system is to cover millions more patients. And, we promised the American citizens that we would provide them the highest quality care while reducing costs.”
RE-LY Investigators: “Wow, that sounds like a great system, but you are aware that newer therapies proven superior are frequently more costly.”
Ms Sebelius: “Any ideas on how will I explain to all these people with AF that we can’t afford to replace the 4$/month warfarin with the hundreds/month dabigatran.”
RE-LY Investigators: “Ms Sebelius, I think we have something that may help you. It took a fair bit of statistical wrangling, but with the right spin, you can probably work with this. You may be interested in our recent Lancet paper. We went back and looked at the original data from RE-LY. You see, on many occasions, statisticians can do post-hoc analysis with arbitrary sub-groups and secondary end-points.”
Ms Sebelius: “Yes, tell me more about this recent retrospective look at the RE-LY trial.”
Re-LY Investigators: “First we separated the warfarin patients into 4 arbitrary quartiles of TTR (time in therapeutic range.) Then, if we consider composite endpoints (a combination of end-points) and mortality, we can say that dabigatran was superior to warfarin primarily when warfarin patients had poorly controlled INRs.”
Ms Sebelius: “So we could say that as long as warfarin patients are in therapeutic range there was little benefit to dabigatran.”
RE-LY Investigators: “You could say that, but most doctors know that no one is able to successfully control the INR (blood thinness) with warfarin. It is a terribly difficult drug to use; even in rigorously controlled trials, the INR is in therapeutic range only 2/3 of the time. Dabigatran avoids this problem.”
Ms Sebelius: “I see. Let me think a moment…Butâ€¦we could say this is a new healthcare system, with EMR. Yes, EMR…that will surely help us keep patients better controlled. Indeed, yes, EMR, that is the answer.”
RE-LY Investigators: “You should also know that there are many other oral anticoagulants in the pipeline, most of which have preliminary data that look favorable to warfarin as well.”
Ms Sebelius: “Helloâ€¦Helloâ€¦There must be a bad connection. Oh well.”
I can’t way to see how this plays out. My guess is that the dreaded blood thinner, warfarin, is going to look a lot less terrible when compared to the expensive alternative.
We will see.
Another h/t to Larry Husten at Cardiobrief for bringing this story to light.