Drug dosing for older heart patients should differ
Difficult to identify the right dose of anti-clotting
medications for the elderly after a heart attack
16, 2013 - Older heart patients present unique challenges for
determining the optimal dosages of medications, so a new study from
researchers at Duke Medicine offers some rare clarity about the use of
drugs that are used to treat patients with heart attacks.
For certain heart patients older than age 75, a
half-dose of the anti-platelet drug prasugrel works about as well as the
typical dosage of clopidogrel, according to a team led by the Duke
Clinical Research Institute, Durham, N.C., that looked at a sub-study of
a large clinical trial.
"As people live longer throughout the world, it's
increasingly important to establish appropriate treatments for
conditions such as acute coronary syndromes that commonly occur later in
life," said Matthew T. Roe, M.D., MHS, associate professor of medicine
at Duke and lead author of a study published Aug. 20, 2013, in the
"These patients are very vulnerable to side
effects, including bleeding, if therapies are not properly dosed," Roe
"Additionally, existing practice guidelines have
few specific recommendations for older patients with acute coronary
syndromes as little evidence has been accrued from prior clinical trials
in this population."
People older than age 75 comprise less than 10
percent of the U.S. population, but account for 35 percent of patients
with acute coronary syndrome (ACS), which includes a recent heart attack
or unstable chest pain. ACS is typically treated with anti-platelet
Earlier studies, for example, had shown that the
platelet inhibitor prasugrel reduced the risk of adverse outcomes
compared with clopidogrel in ACS patients undergoing coronary stent
implantation. Those studies used a 60-mg initial dose followed by a
10-mg/day maintenance dose.
At that dosage level, however, patients older than
age 75 had an increased risk of intracranial and fatal bleeding, as did
younger patients weighing 132 pounds or less. The results led to
warnings by the U.S. Food and Drug Administration and the European
Medicines Agency for the use of the 10 mg/day maintenance dose of
prasugrel in those populations, and consideration of a reduced dose (5
mg/day) to mitigate bleeding complications.
To examine whether older patients might benefit
from a lower dosage of prasugrel, the Duke-led researchers analyzed more
than 2,000 older patients who participated in a large trial called
TRILOGY ACS that compared prasugrel with clopidogrel to manage acute
coronary syndromes without coronary stent implantation or coronary
The findings from this study, the first long-term
data on outcomes specifically from elderly patients treated with the
reduced dose of prasugrel, determined that a smaller dosage of 5-mg/day
of prasugrel presented no greater risk of bleeding problems than the
commonly prescribed 75-mg dose of clopidogrel in the elderly population.
"The findings from our study indicate how difficult
it is to identify the right dose of anti-clotting medications for the
elderly, to improve outcomes after a heart attack," said co-author
Magnus Ohman, professor of medicine at Duke and chairman of the TRILOGY
ACS study. "While a lower dose seemed intuitive, it was safe but not
more effective. Future dedicated studies need to continue to find the
right therapies for the vulnerable elderly patients."
In addition to Roe and Ohman, study authors include
Shaun Goodman; Susanna Stevens; Judith Hochman; Shmuel Gottlieb; Bikur
Cholim; Felipe Martinez; Anthony Dalby; William Boden; Harvey White;
Dorairaj Prabhakaran; Kenneth Winters; Philip Aylward; Jean-Pierre
Bassand; Darren McGuire; Diego Ardissino; Keith A.A. Fox; and Paul
The drug companies Eli Lilly and Daiichi Sankyo,
which market and make prasugrel, funded the TRILOGY ACS study.
Roe receives grant funding and/or consulting fees
from Lilly and Daiichi Sankyo. Ohman receives grant funding and travel
expenses from the Lilly and Daiichi Sankyo. More detailed disclosures
are provided in the published study.
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