Quick question- how soon after a PE after a right ventricular outflow tract tachycardia can one fly on an airplane.

There's no exact duration of time after PE when flying is prohibited.  If a patient feels well, has no chest discomfort or shortness of breath at rest, and is fully and stably anticoagulated, then flying should generally be OK.--SZG

Two questions: !. For patients in their sixties with AF episodes of only a few seconds, almost daily but noticed by the patient - would you anticoagulate och and/or prescribe an antiarrhythmic? 2. Did the RE-LY study differentiate patients on warfarin with stroke according to whether at therapeutic INR level? If a patient's INR is perfectly stable, is he at equivalent or higher risk for stroke than with dabigatran?

 

 

What about the fact  that there is still no antidote for Dabigatran, it still takes 24 to 36 hrs to reverse the effect of Dabigatran, would you operate during that time period,would you put a patient at risk if an emergency procedure is required?

In a patient with normal renal function, most of the anticoagulant effect of dabigatran will dissipate within 12 hours of the last dose.  In an emergency, such as a patient who has suffered major trauma and needs immediate surgery, dabigatran can be hemodialyzed and removed.--SZG

1. This is a patient with repeated and bothersome episodes of paroxysmal AFibr.  I'd give an antiarrhythmic.  And assuming there were no other risk factors for stroke except for age, I'd prescribe aspirin, not an anticoagulant like warfarin or dabigatran. 

2. A RE-LY substudy addresses exactly the question you ask.  Wallentin L, et al.  Lancet 2010; 376:  975-983.  If the INR is in therapeutic range for about 73% of the time, then the stroke prevention efficacy with warfarin is about the same as with dabigatran.  Conversely, dabigatran prevents the most strokes compared with warfarin when the time in the therapeutic range is low, and when warfarin control is not very good.--SZG 

 

Samuel Goldhaber,

Where did you get the 12 hour time, for dissipation of dabigatran anticoagulation effect?  Do you have a reference?

"If the INR is in therapeutic range for about 73% of the time then the stroke prevention efficacy with warfarin is about the same as with dabigatran. "

 This is actually not true.  At a cTTR of 65.5 warfarin and dabigatran for all doses were basically the same.  At a cTTR (center mean time in theapeutic range) of > 72.5 warfarin significantly beat out dabigatran for many endpoints including four composite endpoints.  Average US time in therapeutic range was 66 therefore it seems that in americans dabigatran offers no advantage especially when you look at a significant increase in MI (NNH = 500) which equals 4400 extra MI/ year or 32,000 extra MI by the year 2016.  Also, there is a significant increase in GI bleed with dabigatran, no antidote, no way to know if someone is compliant, twice daily dosing versus once daily dosing.

 Sincerely,

James DiNicolantonio, Pharm.D.

 

i got a blood clot in my leg in 2009. it never dissolved and apparently has solidified. i have taken warfarin continously up until just recently. i am now taking dabigatran. could you discuss the benifits/risk factors of taking this medication in this situation? will it or is it even possible that the clot will dissolve? does this medication have longterm effects on the kidney? thanks in advance for any insight! Ron!

Ron,

 First dabigatran was approved off of an OPEN-label trial, the RE-LY trial, which isn't RE-LY-able at all.  Even when endpoints are blinded significant bias is introduced.  There are much more gastrointestinal bleeds and myocardial infarctions with dabigatran compared to warfarin.  Dabigatran has a tartaric acid core which causes significantly more nausea, dyspepsia, and stomach upset.  There is no antidote if you start to bleed.  We have no way to monitor if you have been adherant or not.  It's twice daily instead of warfarin, which is once daily, so compliance goes down.  If you miss 2 doses your no longer properly anticoagulated with dabigatran.  Dabigatran costs ten times as much as warfarin.  We do not know the extent of drug interactions with dabigatran but what we know so far is, verapamil increases AUC by 2.5 fold, ketoconazole by 150%, quinidine by 100%, rifampin decreases AUC by 60%.  There are many pgp inhibitors/inducers and we have no way of truly knowing if they affect AUC of dabigatran.  Now the makers of dabigatran, Boehringer Engelheim say that these changes in AUC are not clinically relevant.  However, it seems that AUC changes were clinically relevant in the RE-LY trial.  For example, patients on PPI, which decrease dabigatran AUC by 20-30% did not do as well.  Patients with higher creatinine clearance, and thus less exposure to dabi, as well as patients weighing > 100 kg didn't seem to do as well.  I would not take dabigatran based off the RE-LY trial. 

Lastly the time in therapeutic range (TTR) for warfarin in the US and canada was 66.9%, and when the TTR was 65.5% or more, there was no overall benefit for dabigatran versus warfarin as far as the primary endpoint.  So in US and canada when your controlled well on warfarin, dabigatran is not gona prevent any more strokes, and is clearly not cost effective, or realistic with its greater GI bleed, MI, and dyspepsia.

Sincerely,

James DiNicolantonio, Pharm.D.

Last I had heard,read, the FDA had not yet been approved for Dabigatran to be used for the purpose of anticoagulant therapy for DVT. (unless I have missed out on that press release).

Many doctors, both in the USA and in Canada are prescribing Dabigatran for the purpose of anticoagulant therapy for Deep Vein Thrombosis (I am not talking of patients with atrial fibrillation, I am talking of patients with DEEP VEIN THROMBOSIS) 

Example, the previous poster "Ron".

Last I had read was:

 rhythmia/EP

Dabigatran joins US atrial-fib guidelines

February 15, 2011 | Steve Stiles

Dallas, TX and Washington, DC - The oral anticoagulant dabigatran (Pradaxa, Boehringer Ingelheim), approved by the FDA only few months ago, as expected has entered the US atrial fibrillation (AF) management guidelines as an alternative to warfarin for preventing strokes and thromboembolism [1]

 

http://www.theheart.org/article/1185559.do

 

rrhythmia/EP

FDA approves dabigatran for stroke prevention, embolism, in AF patients

October 20, 2010 | Shelley Wood and Michael O'Riordan

Silver Spring, MD (updated) - Late Tuesday, Boehringer Ingelheim announced that the US FDA has approved dabigatran (Pradaxa) for the prevention of stroke and systemic embolism in  tal [1].

http://www.theheart.org/article/1138703.do

 

Approval and usage

On March 18, 2008, the European Medicines Agency granted marketing authorisation for Pradaxa for the treatment and prevention of thromboembolic disease.^[8]

The National Health Service in Britain authorised the use of dabigatran for use in preventing blood clots in hip and knee surgery patients.

In Canada, approval came on June 13, 2008, for the prevention of blood clots in patients who have undergone total hip or total knee replacement surgery. Approval for atrial fibrillation patients at risk of stroke came in October 2010.^[10]

The U.S. Food and Drug Administration (FDA) approved Pradaxa on October 19, 2010, for prevention of stroke in patients with non-valvular atrial fibrillation.^{[11][12][13][14]} The approval came after an advisory committee recommended the drug for approval on September 20, 2010^[15] although caution is still urged by reviewers.^[16]

Dabigatran was added to the U.S. guidelines with a Class I recommendation on February 14, 2011.

 http://en.wikipedia.org/wiki/Dabigatran

 

 

 

Matter of fact, there was a study which I took part in 2008, RE-MEDY,which is why I know of Dabigatran.

Re-Medy: A phase III, randomised, multicenter, double blind, parallel-group active controlled study to evaluate the efficacy and safety of oral dabigatran etexilate (150 mg bid) compared to warfarin (INR 2.0-3.0) for the secondary prevention of venous thromboembolism.

 

Here are three studies that were held by B&I .

 

RE-COVER TM & RECOVER II  TM           Treatment of acute VTE                          Ongoing trials
 (Results for first RECOVER TM trial expected in  December 2009)

RE-MEDY  TM                                       Secondary prevention of VTE                  Ongoing

RE-SONATE TM                                    Secondary prevention of VTE                  Ongoing

*This data dates from fact sheets from 2009.

http://www.google.ca/search?q=Boehringer+Ingelheim+fact+sheet+on+Dabigatran&ie=utf-8&oe=utf-8&aq=t&rls=org.mozilla:en-US:official&client=firefox-a

Dabigatran isn't FDA approved to treat DVT.

You haven't missed anything.  In fact, as far as I know, no request has yet been made for the FDA to review dabigatran for VTE treatment.  Thus, dabigatran is approved in the USA solely for stroke prevention in nonvalvuar atrial fibrillation.--SZG

RE-MEDY hasn't been published yet.--SZG

Interesting perspective, Henry.

 Thanks for sharing this with the Clot Bloggers.--Sam

  They observed that for 1774 patients who qualified for warfarin, the annual projected costs of anticoagulation management were $1 385 494, made up largely of labor and laboratory work. If all these patients were transitioned to dabigatran, the costs of labor and laboratory work would be eliminated, but the substantial drug costs significantly increase the price of patient management. For these 1774 patients to be treated with dabigatran, the cost of patient management increases to $4 371 136.

http://www.theheart.org/article/1210087.do?utm_campaign=newsletter&utm_medium=email&utm_source=20110415_TopStories_EN

 

Why is the cost quadrupled, if there are no lab and no labor cost?

Do I understand corectly? It is the cost that patients would have to pay...

Given those facts and the choice of dagigatran over warfarin, many patients will remain on warfarin...

Is Dabigatran really the answer?

Contrary to comments above, I do not believe that TTR in RE-LY was shown to effect stroke and embolism rate, although the only analysis was by center. Furthermore, the reduction in ICB  (as opposed to other bleeds) seems independent of TTR. This has been observed with rivaroxaban as well.

Individual TTRs are difficult to compare, as individual characteristics are confounders. Well-controlled patients are more likely to be adherent with a host of other good health behaviors.

I had a Cath Ablation....successful procedure.....36 hours post hosp d/c, on Pradaxa 150mg BID, and Prilosec OTC, I suffered a large ISCHEMIC STROKE = blood clot formed, and lifted/entered bloodstream as embolism, and hit in my brain and got stuck.....very large......DaVinci Procedure saved my life?  From what I've read, antacid use = Omezaprole can/will reduce Dabigatran absorption by up to 30%.  If FDA approved drug for use at 150mg BID, and 100% - 30% = 70%, then 70% x 150mg = 105mg, effective drug available in system for absorption.  couple that with rapid half life between doses, no effective anticlotting going on = blood clot formation....then, WHAM....clot lifted.....Stroke hit like a bolt of lightening!  Health care providers take note...Antacid use and Pradaxa/Dabigatran don't mix......renders anticlotting ineffective.....

Hi. I am looking for any studies related to PPI and Pradaxa and whether or not the concomittant use reduces the efficacy of Pradaxa. Being that Pradaxa absorbs best at a lower Ph I am interested to see if raising the Ph with a PPI decreases the absorbtion.

Thanks

Thanks for your query.

 When the PPI pantoprazole was coadministered with dabigatran, approximately a 30% decrease in the dabigatran AUC was observed.  However, when pantoprazole and other proton pump inhibitors were coadminister4ed with dabigatran in clinical trials such as RELY, there was no reduction in the efficacy of dabigatran.

In healthy elderly subjects, coadministration of dabigatran with pantoprazole decreased the average bioavailability of dabigatran by 20% on Day 7.  The safety profile of dabigatran was good, with and without pantoprazole coadministration (ref:  Stangier J, et al.  Clin Pharmacokinet 2008; 47: 47-59)--SZG