AF Symposium 2015
All Anticoagulants Cause Bleeding
Updated August 2015
Dr. Peter Kowey of Lankenau Hospital in Wynnewood, PA discussed the special needs of patients with both A-Fib and Coronary Artery Disease (CAD). Sometimes, for example, these patients have to take both anticoagulant therapy for A-Fib and antiplatelets for stents. Some patients wind up taking a combination of three different drugs like warfarin, clopidogrel and aspirin.
Dr. Kowey pointed out how taking combinations of anticoagulants and antiplatelets multiplies the risk of bleeding. He cited the WOEST study which, though small, indicated that there was no real need for aspirin in addition to warfarin and clopidogrel.
All Anticoagulants Cause Bleeding
His most important point Dr. Kowey made for A-Fib patients is that all anticoagulants cause bleeding. That’s how they work. What an EP and an A-Fib patient strive for together is to find the right dose that gives the best protection versus minimizing the chances of bleeding. It’s tricky, because there are so many differences among patients. And it changes over time as we do.
NOACs May Be Dose Dependent
Dr. Kowey also discussed how the new anticoagulants (NOACs) were FDA approved on the assumption that one-size-fits-all, that one dosage works for all patients. But we know that warfarin is dose dependent. One would expect intuitively that the NOACs would work in a similar manner.
Dr. Kowey discussed the recent FDA hearings on the new anticoagulant edoxaban (Savaysa), namely that patients who had very good renal function seemed to get less of an anticoagulant effect. Patients taking the previously FDA approved NOACs may have been underdosed, because most of these drugs are renally eliminated. Unlike the INR measure in warfarin, the NOACs don’t have any standard, recognized way of measuring the anticoagulant effect as a guide to dosing. The one-size-fits-all NOAC dosage may work for most people, but others may be over- or under-anticoagulated.
Though not part of Dr. Kowey’s presentation, recent reports on Pradaxa (dabigatran) indicate that Boehringer-Inglehoff may have known that Pradaxa was dose dependent but didn’t tell the FDA. (See Claim “Misguided” That Pradaxa Needs No Blood-Level Monitoring.)
Taking anticoagulants is a trade-off. For most people, lowering the risk of an A-Fib stroke is a most welcome benefit compared to an added tendency to bleed.
All Anticoagulants Cause Bleeding and Are Dangerous
Anticoagulants are not like taking vitamins. No one wants to take an anticoagulant. Dr. Kowey’s statement that “all anticoagulants cause bleeding” and are inherently dangerous should determine how we look at all anticoagulants. This is in stark contrast with how NOACs are presented in today’s TV advertisements. (Just take an anticoagulant and live happily ever after!)
We obviously don’t have any data on the long-term effects of taking NOACS for years. Some people on long-term warfarin have been known to develop micro bleeds and dementia. Will this happen with the NOACs? We simply don’t know. But intuitively one would expect the same thing to happen, though probably not to the extent of warfarin.
NOACs Dose Dependent?
Dr. Kowey’s presentation also highlighted another important point for A-Fib patients—NOACs are probably dose dependent to some extent. One size does not fit all. If you are taking a NOAC, you may be under- or over-dosed.
How serious a problem is this? We simply don’t know. With Pradaxa many people have died in the ER from bleeding that doctors couldn’t stop. Was this because of over-dosing? It’s hard to tell. (See Stop Prescribing or Taking Pradaxa.)
One wonders how the FDA could have approved new anticoagulants with no standard, proven method of determining the anticoagulants’ effectiveness? (The NOACs were also approved with no reversal agent or antidote in case of bleeding!) But to be fair to the FDA, there was a great need for new anticoagulants to alleviate the problems with warfarin. And from the clinical trials, few could have anticipated the real world NOAC problems.
Update August 15, 2015: Reversal Agent for Pradaxa (dabigatran)
An experimental drug, idarucizumad, has show positive results as a reversal agent for Pradaxa (dabigatran). In a new study of 90 patients who had uncontrolled bleeding with Pradaxa, idarucizumad stopped this bleeding within minutes. No serious side effects were reported. FDA approval is pending.
We have previously reported on the reversal agent Andexanet Alfa which is on FDA fast track approval as an antidote to the Factor Xa inhibitors Xarelto and Eliquis. FDA approval is pending.
Update October 26, 2015: FDA Approves Reversal Agent Praxbind® for the Anticoagulant Pradaxa
Last updated: Wednesday, January 27, 2016