Dabigatran approved

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<http://email.theheart.org/cgi-bin1/DM/z/hC6OD0YAFah0b4b0LLLe0Ef> Warfarin,

move over: Dabigatran gets unanimous thumbs-up from FDA advisory panel

Warfarin, move over: Dabigatran gets unanimous thumbs-up from FDA advisory

panel

September 20, 2010 |

<http://www.theheart.org/viewAuthorBio.do?primaryKey=114351> Steve Stiles

Silver Spring, MD - One of cardiology's fondest wishes moved closer to

fulfillment as an FDA advisory panel unanimously recommended approval of a

potential replacement for warfarin

<http://www.theheart.org/viewDocument.do?document=http%3A%2F%2Fwww.theheart.

org%2Fcollection%2FNew-warfarin-competitors.do> in one of the most common

heart disorders. Barring any unforeseen damning revelations about the drug,

the FDA's approval of the oral thrombin inhibitor dabigatran (Pradaxa,

Boehringer Ingelheim) for stroke prevention in atrial fibrillation (AF) is

all but certain.

The panel, with its nine voting members, made the decision based on what's

generally seen as the well-designed, solidly executed 18 000-patient

Randomized <http://www.theheart.org/article/995769.do> Evaluation of

Long-Term Anticoagulant Therapy (RE-LY) trial, which showed dabigatran was

noninferior to warfarin at a lower dosage and superior at a higher one for

preventing thromboembolic stroke in paroxysmal or permanent AF.

Debate among the advisory panel throughout the day was tame; there were few

criticisms of the RE-LY trial's design, little disappointment in the

results, and clear enthusiasm for replacing warfarin in such a widespread

indication.

The panel wasn't charged with voting on a question that provided some of the

only suspense throughout the day, whether the approval should include only

the higher dose, which demonstrated superiority in RE-LY, or perhaps both

dosage levels.

They voted informally nonetheless, with those expressing a preference for

both dosages, generally wanting to give clinicians more flexibility, edging

out those favoring only the higher dose. Some of the latter panelists felt

the lower dose would become the default for clinicians concerned about

safety but at the expense of efficacy.

Warfarin is distinguished in being one of the oldest, one of the most widely

used, one of the most effective, and one of the most disliked drugs in

cardiology: it dramatically cuts ischemic stroke risk in AF but generally

requires tight anticoagulation monitoring to get the dosage right, which can

be arduous for patients and the healthcare system. Patients must also banish

a lot of healthy, vitamin-K-containing foods from their diet.

The kicker with dabigatran, even when " noninferior " to warfarin, is that it

doesn't require anticoagulation monitoring-or major diet changes, for that

matter. And, as the trial suggested and some panelists agreed, at the higher

dose it seems more stroke-preventive than warfarin.

As previously reported by heartwire, RE-LY compared the two dabigatran

dosage levels against a conventional warfarin regimen for the

stroke-prevention indication. Dabigatran was noninferior to warfarin at the

lower dosage and superior at the higher one, the latter achieving a 34%

decline in risk (p<0.001) over a median of two years.

Zavie (age 72)

67 Shoreham Avenue

Ottawa, Canada, K2G 3X3

dxd AUG/99

INF OCT/99 to FEB/00, CHF

No meds FEB/00 to JAN/01

Gleevec since MAR/27/01 (400 mg)

CCR SEP/01. #102 in Zero Club

2.8 log reduction Sep/05

3.0 log reduction Jan/06

2.9 log reduction Feb/07

3.6 log reduction Apr/08

3.6 log reduction Sep/08

3.7 log reduction Jan/09

3.8 log reduction May/09

3.8 log reduction Aug/09

4.0 log reduction Dec/09

4.4 log reduction Apr/10

e-mail: zmiller@...

Tel: 613-726-1117

Fax: 613-482-4801

Cell: 613-282-0204

ID: zaviem