A trial looking at new anti-clotting
drug idraparinux's safety in preventing stroke for atrial
fibrillation (AF) patients had to be halted because
the drug increased brain bleed risk by 74%. The results
are reported in the January 26 issue of The Lancet.
The drug, with its fixed-dose,
no-monitoring-required regimen, seemed like an attractive
alternative to warfarin, a vitamin K antagonist (VKA),
which requires dosage adjustments and close monitoring.
"It looked to be more effective at preventing stroke
and it was hoped that it would be safer," says Dr Alan
Go, assistant director of clinical research at Kaiser
Permanente, Northern California, who co-authored an
accompanying editorial. "But there was major bleeding.
VKAs came out on top."
ROCKY
AMADEUS
The Dutch researchers of the current study randomized
more than 4,500 atrial fibrillation patients in the
Amadeus trial to compare idraparinux with warfarin at
preventing blood clots and stroke. Ten months later,
the trial was stopped due to 346 cases of intracranial
bleeding in the idraparinux arm, mainly in elderly patients
and those with kidney problems who were particularly
vulnerable to complications — the very population
the drug was meant to help.
"Atrial fibrillation is usually
related to age," says Dr Michael Sharma, neurologist
and deputy director of the Canadian Stroke Network.
"Most of the AF patients are elderly — over 60
or 65 — and have at least one other condition like
diabetes or hypertension, so the majority are at risk
of stroke." The lower risk ones get started on aspirin
therapy, though it's not as effective as warfarin, both
docs agree.
WARFARIN
HASSLE
But warfarin is a hassle to administer. It has a narrow
therapeutic range, which means the dose has to be constantly
adjusted, because if it's too low, it won't prevent
stroke and if it's too high, it'll cause hemorrhage.
"When a patient gets started on warfarin, they have
to be monitored every few days in the beginning until
they're stable," says Dr Go. After that, they still
have to get their blood tested every two to six weeks
to adjust the dosage, he adds.
"It takes an investment of time
and effort," Dr Sharma agrees. "And considering the
at-risk population — they're older and retired,
they travel — it's a lot of work."
Most doctors would love to have
another option to warfarin, according to Dr Sharma,
but so far every attempt at finding a replacement has
ended in disappointment. Idraparinux, with its once
weekly injections, would have been a great alternative.
DOWN
BUT NOT OUT
Still, we haven't heard the last of idraparinux, Dr
Go believes. If they change the dosage and format, it
might still benefit some patients, he says. Selecting
the patients who are at higher risk for stroke and lower
risk for hemorrhage might also make it a worthwhile
treatment, Dr Sharma adds.
Idraparinux belongs to a family
of drugs that attack a different step on the clotting
pathway than warfarin and at least one of them has proven
to be highly effective. Fondaparinux, an older version
of idraparinux, is on the market in Canada for prevention
of deep vein thrombosis — with no significant bleeding
issues. Idraparinux is not yet approved here.
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