There was good news today in the atrial fibrillation world.
Though no surprise to heart rhythm doctors, an FDA investigation reveals no evidence that new cases of bleeding are any higher with dabigatran (Pradaxa) than with warfarin.
The full statement from the FDA is here.
The assessment was undertaken because after approval of the novel anticoagulant (blood-thinner) a large number of adverse events were reported to the FDA. Despite conscientious medical opinions, these ‘bad drug’ reports led to a public perception that dabigatran was more dangerous than really dangerous drugs.
Smart folks who looked at these events came to four conclusions:
- Most of the adverse events related to bleeding, which is not surprising with a drug that blocks clotting.
- Early enthusiasm for the first warfarin-replacement drug in decades led to inappropriate use of dabigatran, such as in frail elderly patients or those with chronic kidney disease.
- It was impossible to judge the rate of bleeding events because no one knew how many had been started on the drug. All that was reported was the numerator.
- Adverse outcomes that occur in patients on new drugs get reported more vigorously than events on old drugs. No one would think of reporting a bleeding event with warfarin. These are expected and common. It’s an anticoagulant after all.
The reason why I find this FDA report to be good news is not that it confirms the safety of dabigatran. No drug is completely safe. What gives me hope is that this news might allow us to re-emphasize the most important aspect of AF care:
Shared-decision making.
Of course anticoagulants increase the risk of bleeding events. That’s how they work. The reason why heart-rhythm doctors recommend a drug that increases the risk of bleeding is that it’s the only proven way to reduce the risk of stroke. The higher the risk of stroke, the greater the benefit of the drug. It’s a shared-decision between patient and doctor. A doctor’s job is to guide a patient through this delicate and nuanced decision. It’s about balancing risk: the risk of stroke versus the risk of bleeding.
The thing about stroke: It’s worse than bleeding. There are fewer Mulligans with obstructed blood vessels in the brain. Stroke kills and disables permanently. Bleeding isn’t good either, but far more often than in stroke, patients with bleeds survive unscathed–that is, without a permanent drool or paralysis or life in a nursing home.
You know I don’t like the word need. I don’t tell patients they need to take an anticoagulant. I do my best to tell them of the risks of being on the drug versus being off. Then I try not to be attached to their decision.
JMM
Andy Miller says
November 2, 2012 at 8:17 pmDr John I would like some answers on this.
http://www.prescriptiondrug-info.com/Discuss/Pradaxa-Can-Be-Very-Dangerous-227416.htm
Andy Miller says
November 2, 2012 at 8:49 pmDr. John:
I just searched the death rate for people on site below for Pradaxa and Warfarin there are ten times the deaths from Paradaxa as there are from Warfarin?
http://www.fdable.com/advanced_aers_query/b8aa55759beb19566b0ddae5087e79af
Please advise!
Dr John says
November 2, 2012 at 8:57 pmAndy,
Take a look at the evidence:
http://www.nejm.org/doi/full/10.1056/NEJMoa0905561 >> 18,000 is a lot of patients.
And this: http://m.circ.ahajournals.org/content/early/2012/10/15/CIRCULATIONAHA.112.115410.abstract
Andy Miller says
November 3, 2012 at 11:23 amDr. John:
The statements below come from the first study, you suggested.
The problem I see is major bleeding with dabigatran it is like playing with snakes and not having an anti venom should you get bit. (Sure Death)
I also see 10 times the death rate for dabigatran verses warfarin on FDA’s own web site and dabigatran has only been on the market for some three years!
There was a significantly higher rate of major gastrointestinal bleeding with dabigatran at the 150-mg dose than with warfarin.
The rate of myocardial infarction was 0.53% per year with warfarin and was higher with dabigatran: 0.72% per year in the 110-mg group (relative risk, 1.35; 95% CI, 0.98 to 1.87; P=0.07) and 0.74% per year in the 150-mg group (relative risk, 1.38, 95% CI, 1.00 to 1.91; P=0.048).
On the other hand, as compared with the 110-mg dose, the 150-mg dose of dabigatran was associated with a trend toward an increased risk of major bleeding (P=0.052) and also with increased risks of gastrointestinal, minor, and any bleeding.
The only adverse effect that was significantly more common with dabigatran than with warfarin was dyspepsia (Table 4TABLE 4
Discontinuation of the Study Drug, Adverse Events, and Liver Function According to Treatment Group.
). Dyspepsia occurred in 348 patients (5.8%) in the warfarin group and in 707 patients (11.8%) and 688 patients (11.3%) in the 110-mg and 150-mg dabigatran groups, respectively
This is partly explained by the more inclusive definition of major bleeding in our study. There was an increase in the rate of gastrointestinal bleeding with the higher dabigatran dose, despite the overall lower rates of bleeding at other sites. To enhance absorption of dabigatran, a low pH is required. Therefore, dabigatran capsules contain dabigatran-coated pellets with a tartaric acid core. This acidity may partly explain the increased incidence of dyspeptic symptoms with both dabigatran doses and the increased risk of gastrointestinal bleeding with the 150-mg dose.
(Also putting our bodies at a lower PH makes us more susceptible to other diseases especially cancer!
An
Andrew Bowman says
November 2, 2012 at 9:25 pmThere may not be a higher incidence of bleeding on Pradaxa as opposed to Coumadin but at least with Coumadin I have approaches to reverse it much more readily.
Ken Grauer, MD says
November 3, 2012 at 6:05 amThere is a concern about an increase in cardiac events with Pradaxa (Dabigatran) – and the drug should not be used in frail, older patients with impaired renal function (as you allude to above) – https://www.dropbox.com/s/s7gb38gqefiw4ez/Dabigatran%20Concerns.png – The GOOD news about your post is that you state your views and cite evidence – and leave us with emphasis on shared decision-making. The question of anticoagulation with Chronic AFib leaves us with a number of alternatives – none of which I really like. “Hindsight is 100% in the retrospectoscope” – but MUCH more difficult up front to predict what is the best course for any given patient. Time should ultimately tell. In the meantime – best effort by clinician to explain the situation and assist the patient in shared decision-making appears to be the best policy. Not becoming “attached” to whatever the patient decides as you conclude is optimal. THANKS for posting! This is NOT an easy issue …
Brent Reed says
November 3, 2012 at 9:38 amI like that your post alluded to the importance of appropriate patient selection as a consideration that should precede the shared decision-making discussion. As you describe, I think the overwhelming enthusiasm for an alternative to warfarin led to these conversations being had with patients who should have never even been candidates for dabigatran in the first place — and likely the reason why so many concerns were initially raised over its safety compared to warfarin. One of the issues that I think will make these conversations more challenging moving forward is if/when the discussion involves several alternatives to warfarin: should clinicians present patients with what is, in their professional opinion, the most ideal of the options available (i.e., based on patient-specific characteristics) or present them with all of the alternatives available to them (explaining the subtle differences between efficacy, safety, etc)?
Ken Grauer, MD says
November 3, 2012 at 6:02 pmBrent – You hit upon the “essence” of optimal joint decision-making – which is always a fine balance between providing adequate information to empower the patient and enable him/her to sift through the choices and decide what they feel is best for them – yet not biasing the patient with the clinician’s views – and as Dr. John states in his last sentence, not becoming attached to whatever the patient ends up deciding (regardless of whether that decision is what you the clinician think is best). It is not easy – and each patient is different – but it is by far the BEST way to go for clinical situations such as AFib/Stroke Prevention when each treatment choice has pros and cons …
Dr John says
November 3, 2012 at 8:17 pmKen…
Thank you.
I appreciate your words. You are the best.
Please, keep commenting.