Blood Thinner Blog Posts Worth Reading
Nov19

Blood Thinner Blog Posts Worth Reading

What you're looking at is an overview of the complex biochemical pathway behind blood clotting, and a smattering of the drugs researchers are developing to control clotting for preventing strokes and more. Over at Terra Sigillata, David Kroll has two back-to-back posts about some of these drugs that are worth reading. In the first post, Kroll discusses news out of the American Heart Association's annual meeting: Rivaroxaban (Xarelto), a blood clot preventing drug from Bayer and J&J, has been shown to be about as efficacious as the established medication warfarin (coumadin) and better with regard to spontanous bleeding complications. He also dishes on some of the fascinating historical context behind the drugs. In the second, he brings attention to Pfizer and BMS's announcement that they are halting a trial of apixaban, their investigational blood clot preventing medication. Eight other apixaban trials are ongoing. We covered some apixaban news last June, when a different apixaban clinical trial was stopped early because an independent analysis concluded that the drug candidate was more effective than aspirin at reducing strokes and blood clots in patients with a common abnormal heart rhythm. As we've written in C&EN, many factors will determine whether patients at risk of strokes or other dangerous blood clots will end up taking warfarin or will take one of the new drugs. Boehringer-Ingelheim's Pradaxa (dabigatran), which acts at a different target from apixaban and rivaroxaban, is already approved by FDA. Rivaroxaban and Pradaxa are already approved in a number of other countries for short-term use. Each drug is slightly different, from how many times a day it must be taken, to how much of it is cleared via the kidneys (a potential issue for patients on dialysis or other kidney conditions), and much more. And of course, a big question is what the difference in cost is going to be- warfarin pills are cheap but the quality of life costs- incessant testing and diet monitoring- can be steep. Image:...

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On Blood Thinners And Rat Poison
Aug16

On Blood Thinners And Rat Poison

C&EN's cover story this week is about finding replacements for the blood thinner warfarin, something that hasn't happened in the more than fifty years since the drug went on the market. Warfarin prevents blood clots from forming and reduces active clots as well. When it works, it's great for preventing strokes. As a bonus, it's a dirt cheap pill, costing on the order of a couple of cents a day. But the trouble is that warfarin doesn't always work well. It is extremely unpredictable in the body. Foods and other drugs affect its activity, as do certain genetic traits. The last thing you want to do is to take too much or too little warfarin. Too much warfarin could lead to uncontrolled bleeding, something that can be deadly in a place like the brain. And of course too little warfarin won't be effective at preventing clots. So patients on warfarin must constantly monitor how well their blood is clotting, so their doctor can get their dose just right. The fact that it's easy to overdose on warfarin is a pain for doctors and patients. But it comes in pretty handy in warfarin's other, perhaps less well-known application: rat poison. It seems that messing with rodents' blood clotting pathways is a very efficient way to off them. My cursory research indicates that we've got many rodenticide options, and warfarin isn't the most common one. I couldn't find warfarin at three different D.C. hardware stores. But it's still available online. YOUR KEYWORD FOR THIS BLOG IS: COMING As an aside: medical websites seem to use the name "coumadin", but the rat poison boxes read "warfarin". I'd love to know the history behind this name divergence. It could be another instance of name-changing to assuage patient fears. I can certainly understand how a patient would find it disconcerting to see a giant box of their blood thinner in the pest control aisle at Home Depot. Think of how a nuclear magnetic resonance spectrometer uses essentially the same technology as a magnetic resonance imaging instrument. But the name you see used in the health field drops the...

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BMS and Pfizer’s blood thinner beats aspirin- now, what can it really do?
Jun11

BMS and Pfizer’s blood thinner beats aspirin- now, what can it really do?

Yesterday, Bristol Myers Squibb and Pfizer agreed to stop AVERROES, a late-stage clinical trial of an experimental blood thinner, early. It's relatively rare for a trial to be stopped for positive reasons, but that is what happened here. An independent analysis concluded that the blood thinner, called apixaban, was more effective than aspirin at reducing strokes and blood clots anywhere outside of the brain in patients with atrial fibrillation, a common abnormal heart rhythm. Stroke is a major complication for patients that have this heart problem, and drug companies would like to find a more manageable way to reduce patients' chances of having one. Apixaban is one of a slew of potential new blood thinners in the pipeline that is an oral inhibitor of Factor Xa, a protease enzyme that sits at a key point in the body's complicated blood coagulation cascade. Matthew Herper at Forbes recently broke down how another drug in this same class, Merck's betrixaban, works. One thing to keep in mind is that none of the 5600 patients in this study were taking warfarin, a decades-old blood thinner that's still one of the gold standards for preventing stroke. For patients with atrial fibrillation, warfarin, a vitamin K antagonist that interferes with the coagulation cascade, is generally considered to be a more effective option than aspirin, which prevents blood platelet activation. The patients in the AVERROES trial, BMS's press release explains, were either unable to take or chose not to take warfarin. I can understand the perspective of the folks choosing not to go that route. Warfarin works, it's cheap, and it's also an oral medication, but it's far from perfect. People who take it must be very carefully monitored by a physician, because other drugs and even foods in the diet can alter its effects in the body. And with blood thinners, you're always walking a tightrope- too high a dose can lead to excessive bleeding. Also, some genetic differences can affect how well warfarin will work. Patients who have that genetic makeup might want to have another option that they can take in the form of a pill. But apixaban is still an investigational agent- FDA has yet to approve it. The news in this trial was good news, but given the relative effectiveness of aspirin I'm not sure how surprising it really was to those following this field closely. To get a complete picture of what apixaban can do, it will be good to see what comes of the ongoing ARISTOTLE trial. That trial, like AVERROES, is a Phase III, randomized, double blind clinical trial in patients with atrial fibrillation. But instead of...

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