October 22nd, 2010
Warfarin or Dabigatran? The Thick and Thin of Deciding on an Anticoagulant
Anju Nohria, MD
These four patients are receiving chronic anticoagulation therapy. Read the descriptions of their cases and decide which, if any, of them you would switch to dabigatran.
Case 1
A 69-year-old man with a history of hypertension and colon cancer was found to be in atrial fibrillation during a preoperative assessment for colon resection. Metoprolol was used to control his heart rate, and he underwent cardioversion guided by transesophageal echocardiography. When atrial fibrillation recurred postoperatively, he was started on warfarin. Multiple attempts at electrical and chemical cardioversion have been unsuccessful. Warfarin maintenance therapy has kept his INR values between 2 and 3. The patient is “sick of being poked and prodded” and wants to know whether he can stop the warfarin.
Case 2
A 53-year-old heart-transplant patient had her post-transplant course complicated by biopsy-induced tricuspid regurgitation. After undergoing tricuspid valve replacement with a mechanical tricuspid valve, she has been maintained on warfarin for several years without complications. She woke up one morning with fever, a headache, confusion, and a diffuse rash on her chest. She was treated for presumptive meningitis until her laboratory values revealed an INR of 11. A head CT scan identified a large frontal intracerebral hemorrhage, and her INR spike was aggressively reversed with vitamin K and fresh frozen plasma. She was monitored with serial echocardiograms and head CTs while off anticoagulation treatment. When she stabilized, warfarin was cautiously resumed.
Case 3
A 33-year-old woman with a history of adriamycin-induced cardiomyopathy, cardiogenic cirrhosis, and atrial fibrillation is maintained on warfarin but is extremely nonadherent to her schedule of INR checks and clinic visits. When measured, her INR values have ranged from 2.0 to 5.6. She has had no major complications from anticoagulation therapy, except for menometrorrhagia.
Case 4
A 35-year-old man has antiphospholipid antibody syndrome and multiple pulmonary emboli despite therapeutic anticoagulation with warfarin and INR values between 3 and 4. His warfarin was discontinued, and he has been maintained on fondaparinux without any further events. The patient’s health insurance does not cover fondaparinux, and he wants to know whether a cheaper alternative is available.
Questions
1) Which of these four patients would you consider switching to dabigatran? Why or why not?
2) Would you consider cost in each case?
3) Would the potential for improved quality of life be an adequate reason to switch any of these patients to dabigatran?
For more of our coverage on dabigatran, check out the Dabigatran Resource Round-Up.
7 Responses to “Warfarin or Dabigatran? The Thick and Thin of Deciding on an Anticoagulant”
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cases 1 2 3. Not appropriate for case 4. Case 1 would be dependent on cost. He has CHADS score of 1 and aspirin is reasonable consideration. Also, he is doing well on warfarin and it would provide better stroke prevention than aspirin. Dabigatran would be a reasonable consideration, if he was unhappy with monitoring warfarin and was willing to accept the expense of Dabigatran. Cases 2 and 3 would likely do much better on Dabigatran presuming cost was acceptable.
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Oops. Case 3 has cirrhosis. She likely won’t do will given here noncompliance with INR checks and clinic visits and her sever disease burden. She might be happier and safer with home INR monitoring.
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Case 1 can be switched to Dabigatran without problems. Case 2,3 and 4 would have been excluded f rom participation to the Re-ly trial, therefore we can’t be sure that the benefits found in that trial can be obtained in these three patients.
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I received speaking compensation in some BI organized meeting.
In general I would agree w Dr Fresco but that pt only has a CHADS score of 1 and I might queston AC therapy in her. BTW is the CHADS score applicable for Dabigatran ? It was devised for relative risk, benefit for warfarin. If the bleeding risk is lower, would it improve the relative benefit ?
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Interesting point Paul…the CHADS2 score grossly predicts stroke rate. This is fixed. The threshold for anticoagulation may change with dabigatran, as ICB risk is lower. I imagine that a formal risk-benefit analysis would favor dabig for CHADS2 of 1 rather than” optional” for warfarin.
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Speaker for BI
I would treat the patients in cases 1 and 3 with dabigatran. I wouldn’t feel comfortable treating the patient’s in cases 2 and 4 with the new drug because it has not been tested in those specific settings.
With regards to case 1, I am in favor of treatment with anticoagulation even with a CHADS(2) score of just 1. RE-LY demonstrated dabigatran 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage; I agree with other comments that this changes the risk-benefit ratio of anticoagulation, probably in favor of anticoagulation. Dabigatran is a cost-effective alternative to warfarin that would spare this patient pokes and improve his quality of life.
(Article to support cost-effectiveness: Freeman et al. Cost-Effectiveness of Dabigatran Compared With Warfarin for Stroke Prevention in Atrial Fibrillation; Annals of Internal Medicine November 2, 2010, 153 (9)) –> at 237/month, it would not be cheap, but it may be cost effective….
For case 3, on one hand, taking a tablet twice a day (like dabigatran) may be more difficult than a once-a-day pill (warfarin) which would increase the risk of insufficient anticoagulation. On the other hand, it allows predictable anticoagulation. I don’t believe that stable liver disease is a contraindication. I would treat this patient with the more reliable dabigatran to decrease risk of hemorrhage from supratherapeutic INR.
(Stangier et al.: Pharmacokinetics and Pharmacodynamics of Dabigatran Etexilate, an Oral Direct Thrombin Inhibitor, Are Not Affected by Moderate Hepatic Impairment; J Clin Pharmacol December 2008 vol. 48 no. 12 1411-1419).
Regarding case 2: Dabigatran has not been tested for or approved for anticoagulation for mechanical valves. There is no role, yet.
Regarding case 4: I’m not aware of studies of dabigatran for prevention of thromobotic events in anti-phospholipid syndrome.
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Case 1 and 3 seem worth a treatment with dabigatran.
In case 1 the patient openly demand a less “invasive” treatment and dabigatran 150 doesn’t need lab controls.It is true that the CHADS score in this patient is 1, but in a cancer patient, lack of trial evidence notwithstanding, it is reasonable to assume a coagulation balance shift toward clotting (as it happens in the venous system, in which the main mechanism of thrombosis is stasis, as in atria, during AF).
In case 3, there is an unacceptable variability of INR values, exposing the patients both to thromboembolism and haemorrhage.
Dabigatran seems the better solution, given the more predictable and stable effect on coagulation.
Case 2 is related to an extreme increase on INR during the warfarin treatment; in this case I would investigate and possibly remove the causes of this phenomenon and try to get on with warfarin, also given the lack on data about treatment with dabigatran in mechanical valves.
In case 4, fondaparinux seems to work efficiently and I don’t think that switching to dabigatran could afford better results (anyone aware of a comparison between the two drugs?).
Competing interests pertaining specifically to this post, comment, or both:
None