December 7th, 2009

Dabigatran vs Warfarin: War or Peace?

CardioExchange Editors: Given the results of both your RE-COVER study and the recently published RE-LY study, should anybody still be using warfarin?

Goldhaber: Warfarin is not going to fade away into oblivion.  Anyone currently stable on warfarin has little reason to abandon this time-tested drug.  If once monthly INRs are usually in the therapeutic range, and if there have been no bleeding or clotting complications, why “rock the boat”?  By the way, warfarin’s fighting back.  It’s been around since 1954, so we know all of its potential complications.  And it’s inexpensive.  With a large ongoing NHLBI trial to test rapid turnaround genetic testing to prescribe a more precise starting dose of warfarin, and with (mostly) insurance-reimbursed point-of-care fingerstick self-testing of INR, effective prescription of warfarin is more widespread now than ever before.  Keep in mind that nurse and pharmacist-run Anticoagulation Clinics have also enhanced the safety and efficacy of warfarin prescription. Finally, dabigatran has not been tested in important thrombotic conditions such as for prophylaxis against venous thromboembolism during hospitalization for medical illness or for prevention of thrombosis with mechanical prosthetic heart valves.  At the moment, dabigatran is not FDA approved for any condition in the United States.  And nowhere has it yet received regulatory approval for stroke prevention in atrial fibrillation or for treatment (along with a required initial course of low molecular weight heparin or fondaparinux) for acute venous thromboembolism.

CardioExchange Editors: If it were to receive FDA approval, what situations would you consider to be prohibitive for dabigatran?

Very few.  Inability to comply with a twice daily medication.  Renal failure.  Gastric discomfort not alleviated by taking dabigatran with food.  Keep in mind that a small minority of patients (3%) suffers excruciating gastric discomfort.  They can’t tolerate dabigatran and should use warfarin.  Contraindications also include any active bleeding condition or bleeding predisposition that would ordinarily prohibit use of warfarin.

CardioExchange Editors:
Given that very few patients in RE-COVER had even mild renal dysfunction, how cautious do you think we should be in situations where the creatinine clearance is above 30 but below 50 ml/minute, knowing that dabigatran is 80% renally excreted?

We need to be cautious using dabigatran in patients with chronic kidney disease, especially the creatinine clearance might drift down below 30 ml/minute.  Major bleeding is an ominous prognostic sign for patients with either arterial or venous thrombotic illness.  Patients with renal failure (creatinine clearance <30 ml/minute) should use warfarin, which is metabolized by the liver, not the kidney.

CardioExchange Editors:
Although the difference was not statistically significant, people with a prior VTE appeared to do better on warfarin versus dabigatran in RE-COVER.  Why might this be the case?

It has been long observed by “blood clot docs” that patients who are established on warfarin and clinically stable have much better control of the INR and far fewer problems than “warfarin naïve” patients.  So, I’d expect that these patients already taking warfarin are, in a sense, pre-selected to do well.  All the kinks of anticoagulation have been pretty much been worked out for them.

Comments are closed on this post, but please join the conversation at our Dabigatran Resource Round-Up.

4 Responses to “Dabigatran vs Warfarin: War or Peace?”

  1. A Look to the Future…

    Really interesting comments about the clinical importance of warfarin. Do you think that in the coming era of pharmacogenomic testing, we may see a time when people get point-of-care testing with respect to their suitability for warfarin versus an alternate anticoagulant such as dabigatran? The analogy that comes to mind is possible point-of-care testing for anti-platelet drugs which may offer the possibility of “personalized medicine.”

  2. What about weight/BMI?

    In the RE-LY study of afib patients, the benefits of dabigatran over coumadin were not observed in the patients >100kg (suggesting that 150mg bid may not be the ideal dose for these patients). Did you see the same in RE-COVER?

  3. Re: A Look to the Future

    Hi Nihar, The technology already exists to devise point-of-care testing for pharmacogenomics affecting warfarin dosing. However, this approach has not been commercialized because it remains uncertain whether routine, rapid turnaround genetic testing will ultimately benefit patients who are about to initiate warfarin and whether such an approach will be worth the expense. We should have a definite “yes” or “no” answer by 2013, when the COAG Trial sponsored by the NHLBI is published. In the future, it might be that patients who are predicted to be outliers requiring really high or low doses of warfarin will be especially good candidates for fixed dose oral anticoagulants.

  4. Re: What About Weight/BMI?

    Dear Rick,

    We looked at every variable we could think of when we analyzed the results of RE-COVER. And a heavy weight didn’t stick out as a “bad actor.” In this respect, it is reassuring that RE-COVER used the higher dose (150 mg BID) of the two doses used in RE-LY.