NEWS: Pricey drug could cut stroke rate

[poledriver]

Pricey drug could cut stroke rate

A FIGHT about the funding of a new drug that is claimed could reduce strokes in Australia by 5700 a year is posing a fresh challenge to the Gillard government's attempt to rein in pharmaceutical costs.

The drug, Pradaxa, which international research has found can reduce strokes by 36 per cent and supplants the hazardous alternative drug, warfarin, has received expert approval in Australia.
But the government has hedged at subsidising the drug, which it has estimated could cost taxpayers $1 billion in four years.

The Health Minister, Nicola Roxon, has called for another review of the drug, proposing a rethink to encourage use of the much cheaper warfarin, which is associated with a much higher risk of haemorrhages in the brain.

In the most aggressive campaign yet launched by a drug company to secure listing of a product, the drug's manufacturer, Boehringer Ingelheim, is pressing doctors and patients to petition the government for its listing on the Pharmaceutical Benefits Scheme.
A website includes a meter showing the number of strokes - 500 - the company estimates have occurred due to Pradaxa's unavailability since the government's review announcement slightly more than a month ago.

The company has also commissioned a report by a consulting firm, which has estimated the drug would reduce strokes in Australia by 15 a day if it were administered to patients with untreated irregular heartbeat conditions at moderate-to-high risk of stroke.​

here

 

[L3inad]

Pricey drug could cut stroke rate
The drug, Pradaxa, which international research has found can reduce strokes by 36 per cent and supplants the hazardous alternative drug, warfarin, has received expert approval in Australia.
But the government has hedged at subsidising the drug, which it has estimated could cost taxpayers $1 billion in four years.

The Health Minister, Nicola Roxon, has called for another review of the drug, proposing a rethink to encourage use of the much cheaper warfarin, which is associated with a much higher risk of haemorrhages in the brain.

Warfarin - rat poison.

It might be cheaper, but seemingly less effective. I think they should also include the cost of constantly monitoring warfarin dose with blood tests to keep plama levels within the thereputic range. Allowed to go above this, and haemorrhages occur.

That alone would likely double the cost of treatment wouldnt it? Or maybe blood monitoring is required with this new drug to?

36% isnt an amazing figure by any means. Placebo pills have ~30% success rate if I'm not wrong, so any new drug has to perform better than that to be marketable.

 

[Divine Moments]

It potentially is a better alternative, but there's more to the story. One important fact is that Pradaxa (at the moment at least) can't easily be reversed, which is one of the advantages of heparin and warfarin. If you bleed on it, even 2-3 hours of dialysis will only remove about 60% of the drug. This story, like almost any news story, isn't there to present a balanced view...

36% isnt an amazing figure by any means. Placebo pills have ~30% success rate if I'm not wrong, so any new drug has to perform better than that to be marketable.

I haven't looked at the study, but in a situation like this where it would surely be unethical to place patients who need anticoagulation on a placebo it should be comparing the new drug against current best practice (i.e. warfarin). I doubt they'd be able to claim to reduce the stroke rate by so much if they had only compared it to placebo. (EDIT: in retrospect I may be giving them far too much credit here...)

Also I'd be very suprised if the placebo effect had a 30% success rate in preventing stroke - placebos have greatly varying efficacies depending on what outcome is being tested.

 

[L3inad]

I haven't looked at the study, but in a situation like this where it would surely be unethical to place patients who need anticoagulation on a placebo it should be comparing the new drug against current best practice (i.e. warfarin). I doubt they'd be able to claim to reduce the stroke rate by so much if they had only compared it to placebo. (EDIT: in retrospect I may be giving them far too much credit here...)

Also I'd be very suprised if the placebo effect had a 30% success rate in preventing stroke - placebos have greatly varying efficacies depending on what outcome is being tested.

I think you may be right. That figure I quoted I think was actually from studies that found placebo treatment to be effective in ~30% of individuals. Not that it would actually reduce the stroke rate by 30%.
Also with the varying efficacies, I think that would have been for treatment of psychological disorders rather than phsyical as we have here.

So maybe a 36% reduction in stroke is pretty cool after all

One important fact is that Pradaxa (at the moment at least) can't easily be reversed, which is one of the advantages of heparin and warfarin. If you bleed on it, even 2-3 hours of dialysis will only remove about 60% of the drug

Can loose alot of blood in 3 hours lol. But chances of bleeding seem to be significantly reduced with this drug, I find it hard to believe it cant be reversed. I'm way to fried to fully read up on its pharmacodynamics right now, but surely administration of clotting factors or something along those lines would be quicker than dialysis?

 

[Mr Blonde]

^ Regarding the reversal problem; it seems as if the article got it's information from the Wikipedia page, which doesn't give a source for the line about it not being as reversible as warfarin. Looking at the product information for Pradaxa:

10 OVERDOSAGE
Accidental overdose may lead to hemorrhagic complications. There is no antidote to dabigatran etexilate or dabigatran. In the event of hemorrhagic complications,
initiate appropriate clinical support, discontinue treatment with PRADAXA, and investigate the source of bleeding. Dabigatran is primarily excreted in the urine;
therefore, maintain adequate diuresis. Dabigatran can be dialyzed (protein binding is low), with the removal of about 60% of drug over 2 to 3 hours; however, data
supporting this approach are limited. Consider surgical hemostasis or the transfusion of fresh frozen plasma or red blood cells. There is some experimental evidence to
support the role of activated prothrombin complex concentrates (e.g., FEIBA), or recombinant Factor VIIa, or concentrates of coagulation factors II, IX or X; however,
their usefulness in clinical settings has not been established. Consider administration of platelet concentrates in cases where thrombocytopenia is present or long-acting
antiplatelet drugs have been used. Measurement of aPTT or ECT may help guide therapy [see Clinical Pharmacology (12.2)].

It seems more as if they just haven't investigated treatment options for overdose as extensively as they have been explored for other anti-coagulants.

 

[Divine Moments]

I agree, it's unlikely that it's not possible to reverse the effects (at least significantly, if not completely), but you'd think doctors would want to know how to do so before everyone starts using it

 

[Divine Moments]

If anyone's interested in this topic, here's an article that was posted yesterday out of the USA:

FDA Investigating Serious Bleeding Events With Dabigatran

December 7, 2011 (Rockville, Maryland) — The US Food and Drug Administration (FDA) announced today that it is now investigating postmarketing reports of serious bleeding events in patients taking dabigatran etexilate (Pradaxa, Boehringer Ingelheim) [1].

"FDA is working to determine whether the reports of bleeding in patients taking Pradaxa are occurring more commonly than would be expected, based on observations in the large clinical trial that supported the approval of Pradaxa," according to the drug safety communication issued by the agency.

That large clinical trial is RE-LY. As reported previously by heartwire , rates of fatal bleeding were numerically lower with the higher dose tested in the trial--150 mg twice daily--at 0.23% per year (230 per 100 000 patient-years) compared with warfarin at 0.33% per year (330 per 100 000 patient-years). Life-threatening bleeds were more common, numerically, in the 150-mg group than in the 110-mg group tested in the trial. The 110-mg dose was not approved by the FDA, although it is on other worldwide markets.

Bleeding events with dabigatran have already prompted safety advisories in Japan and Australia and have led to labeling updates in Europe and the US focusing on the need for monitoring renal function. In November, Boehringer Ingelheim confirmed that between March 2008 and October 31, 2011 there were 260 fatal bleeding events worldwide.

The FDA said it will inform the public and clinicians about any new information about bleeding risks when it becomes available. In the meantime, the agency said it believes the anticoagulant provides an important health benefit when used as directed and that patients taking dabigatran should not stop taking the drug without talking to their doctor.

The FDA also noted that physicians should report adverse events or side effects related to dabigatran use to the FDA's MedWatch Safety Information and Adverse Event Reporting Program.

 

[Mr Blonde]

^ Thanks Divine, I got an email alert yesterday about the FDA investigation into these reports but hadn't gotten around to looking at it yet. Interesting news.