New Platelet Blocker Reduces Clots, Artery-Opening Surgery in PAD Patients
Vorapaxar is first in a new class of anti-platelet drugs called PAR-1 antagonists
The illustration shows
how P.A.D. can affect arteries in the legs. Figure A shows a normal artery with normal blood flow. The inset image shows a
cross-section of the normal artery. Figure B shows an artery with plaque buildup that's partially blocking blood flow. The inset image
shows a cross-section of the narrowed artery.
June 20, 2012 - An investigational platelet-blocking drug reduced the rate of dangerous blood
clots in the legs and the need for artery-opening surgery in people with peripheral artery disease (PAD). Unfortunately, the drug didn't
significantly reduce the risk of heart attack or stroke, and those taking the blood thinner had higher rates of serious bleeding incidents.
The new research on vorapaxar was presented in the American Heart Association's Emerging
Science Series webinar.
"Much of the focus on PAD therapies has been on lowering patients' risk of heart attack and
stroke, but this shows that there can be therapies that reduce limb-threatening blood clots and the need for revascularization procedures in
the legs," said Marc P. Bonaca, M.D., M.P.H., Instructor of medicine at Harvard Medical School and Brigham and Women's Hospital in Boston,
Mass., and an investigator with the Thrombolysis in Myocardial Infarction (TIMI) study group.
In the study, researchers randomized 3,787 patients with PAD to receive standard care or
standard care plus vorapaxar.
Participants were part of the 26,449-patient TRA2P-TIMI 50 trial testing 2.5 milligrams per
day (mg/day) of vorapaxar in people with a history of heart attack, stroke or PAD.
The TRA2P-TIMI 50 trial main results presented earlier this year showed a statistically
significant reduction in cardiovascular events including heart attack, stroke, and cardiovascular death with vorapaxar.
In this substudy, focused on participants with PAD, 11.3 percent of those taking vorapaxar
experienced these major cardiovascular events compared with 11.9 percent of those taking a placebo -- a numeric reduction consistent with the
overall trial findings that did not reach statistical significance on its own. However, they found benefits of vorapaxar on limb events.
Compared to those not receiving the drug:
● Fewer vorapaxar patients were hospitalized for blood clots in the limbs
(2.3 percent vs. 3.9 percent).
● Fewer vorapaxar patients required revascularization to restore full
blood flow in narrowed or blocked vessels in the limbs (18.4 percent vs.
Peripheral arterial disease (PAD) happens when there is a narrowing of the blood
vessels outside of your heart.
cause of PAD is
atherosclerosis. This happens when plaque, a substance made up of fat and
cholesterol, builds up on the walls of the arteries that supply blood to the arms
plaque causes the arteries to narrow or become blocked. This can reduce or stop
blood flow, usually to the legs, causing them to hurt or feel numb.
severe enough, blocked blood flow can cause
death. If this condition is left untreated, a foot or leg may need to be
person with PAD also has an increased risk of heart attack, stroke and transient
ischemic attack. You can often stop or reverse the buildup of plaque in the
arteries with dietary changes, exercise, and efforts to lower high
cholesterol levels and
high blood pressure.
"This is the first outpatient therapy that has been shown to reduce the risk of blood clots
and the need for artery opening revascularization procedures in the legs in patients with PAD," Bonaca said.
The reduction in both urgent blood clots as well as the need for surgery to treat worsening
atherosclerosis suggests that the drug may be working in more than one way.
"The target for this therapy is expressed on platelets but also on cells in the artery walls
that are important for normal artery function. The benefits observed may be due to drug activity at both sites," noted Bonaca.
Moderate and severe bleeding was increased in patients on vorapaxar compared to those on
standard care (7.4 percent vs. 4.5 percent consistent with the overall trial); however, there was no increase in fatal bleeding.
"For clinicians and researchers, these data show the potential for therapies that can reduce
leg problems in patients with PAD rather than just overall cardiovascular risk," Bonaca said.
The investigators are analyzing whether vorapaxar treatment improves circulation in the lower
body, or allows patients to walk further without pain due to insufficient blood flow to leg muscles (claudication). All of the PAD patients in
the study initially had symptoms of claudication, and either poor leg circulation or a previous vessel-opening procedure.
Merck funded the study that was co-authored by David A. Morrow, M.D., M.P.H., and Eugene