High-Dose Plavix Misses Goal But Helps Some In Study
August 30 2009 - 1:30AM
Dow Jones News
A double dose of popular anti-clotting drug Plavix failed to
meet researchers' primary goal of preventing more heart attacks,
deaths and strokes than the standard dose -- and it increased the
risk of bleeding -- in a large new study of heart patients.
But the 25,000-patient trial did show that within a subgroup of
patients -- those undergoing a common artery-opening procedure --
the higher Plavix dose was able to prevent more heart attacks and
certain procedure complications than the standard dose. Using a
different measure of bleeding, there also was no significant
difference between high- and standard-dose Plavix, a blockbuster
drug co-marketed by Bristol-Myers Squibb Co. (BMY) and
Sanofi-Aventis (SNY), which funded the new study.
Although the study missed its primary goal, the positive
subgroup finding could support use of the higher Plavix dose. That
could help mitigate the competitive threat to Plavix posed by a new
anti-clotting drug, Effient, from Eli Lilly & Co. (LLY) and
Daiichi Sankyo Co. (4568.TO). A previous clinical trial showed
Effient to be superior to standard-dose Plavix, but with an
increased risk of major bleeding.
Still, some doctors might view Effient as a good alternative due
to concerns that genetic variants in some patients, and use of
heartburn drugs, can reduce the effectiveness of Plavix.
With $8.6 billion in global sales in 2008, Plavix is the No. 2
prescription drug in global sales behind Pfizer Inc.'s (PFE)
Lipitor cholesterol drug, according to drug-data provider IMS
Health.
Results of the new Plavix study, conducted in nearly 40
countries and titled "Current-Oasis 7," are to be presented Sunday
at the annual meeting of the European Society of Cardiology in
Barcelona, Spain.
Plavix was tested in people with chest pain or symptoms of heart
attack who were candidates for an artery-opening procedure in which
tiny devices called stents are sometimes inserted. The patients
were randomly assigned to receive various dose-level combinations
of Plavix and aspirin. The high dose of Plavix was given for seven
days. Not all patients ended up getting the artery-opening
procedure.
At 30 days after start of treatment, the combined rates of
cardiovascular death, heart attack and stroke occurred in
approximately 4.4% of patients on standard-dose Plavix, versus 4.2%
for the double dose, a statistically insignificant difference, said
Shamir Mehta, professor of medicine at McMaster University in
Ontario and lead author of the study.
The risk of major bleeding as defined in the study's design
increased to 2.5% of high-dose Plavix users from 2% in standard
dose. Mehta said the increase was driven largely by bleeding events
requiring blood transfusions. Using a different definition of major
bleeding, there was no significant difference between the groups,
he said.
About 70% of the study's population underwent artery procedures.
Of these, the combined rate of cardiovascular death, heart attack
and stroke was reduced to about 3.9% for high-dose Plavix versus
4.5% for standard dose, Mehta said. The rate of blood clots that
can occur in stent recipients, also known as stent thrombosis, was
reduced to 0.7% among high-dose users from 1.2% for standard
dose.
The benefit of doubling up on Plavix, however, was muted in the
30% of the study's population who didn't undergo the artery-opening
procedure. There was no significant difference in efficacy rates
between high- and standard-dose Plavix users among these
patients.
The same study found no significant differences in efficacy or
safety between a high dose of aspirin and a lower dose.
Many doctors already use a higher initial dose of Plavix. Mehta
thinks the study's findings will reinforce this practice. And
because the double dose was only used for seven days, he said,
"it's negligible in terms of cost implications." Plavix costs about
$4.60 per tablet, and Effient is about $5.45 per pill; prices may
vary by retailer or health plan.
Some doctors still may opt for Effient in certain patients,
including those with a high risk of stent thrombosis and low risk
of bleeding. Magnus Ohman, a professor of medicine at Duke
University who is involved in an ongoing study of Effient, said
"the purists will say [the Plavix] trial didn't meet its endpoint
and it had a signal on bleeding." But he said the downsides
appeared to be overcome in patients undergoing the artery
procedure.
-By Peter Loftus; Dow Jones Newswires; 215-656-8289;
peter.loftus@dowjones.com