The Canadian Diabetes
Association's latest awareness campaign tagets CVD
Photo credit: Canadian Diabetes
Association |
Aspirin resistance is higher in
diabetics than non-diabetics, according to a recent
study presented at the annual meeting of the American
College of Cardiology by Dr Paul A Gurbel, head of cardiology
at Sinai Hospital in Baltimore. The study suggests that
diabetics — many of whom are plagued by comorbid
heart disease — are resistant to the cardioprotective
effects of low-dose aspirin therapy.
ONE
DOSE FITS SOME
"The benefits of aspirin are lower in reducing strokes
in diabetics than non-diabetics," confirms Dr Ravi Retnakaran,
MD, endocrinologist at the Leadership Sinai Diabetes
Centre at Mount Sinai in Toronto. Clinical resistance
measures get a nod from the study presented to the ACC
by Dr Gurbel, which employed physiological measures
of aspirin resistance.
The study compared 30 diabetics
(either type I or II diabetes mellitus) with 90 non-diabetics;
all 120 subjects had cardiovascular disease (CVD). Patients
each got three aspirin doses - 81, 162, or 325mg —
for four weeks per dose. Measures, including platelet
aggregation and thromboxane levels, were taken after
each dose. Resistance was defined by a predetermined
cutoff point. With the 81mg dose of aspirin, resistance
was detected in diabetics, occurring in 13-37% of patients
— depending on the measure used — compared
with 3-14 % of non-diabetics. Higher doses changed this,
notes Dr Gurbel. "Unlike with low doses of aspirin,
where prevalence of resistance was high in diabetics,
increasing the dose got resistance rates to fall, approaching
those found in non-diabetics," he explains, speaking
from his Baltimore office.
Some assays revealed resistance
in diabetics, but this wasn't the case in direct measures
of COX-1 blockade — most commonly understood to
mediate aspirin's antithrombotic effects. "We saw dose
dependent resistance, such as with collagen-induced
aggregation, despite evidence of a blockade of COX-1."
Additionally, adenosine diphosphate-induced platelet
aggregation was lower in diabetics, but in this case
resistance persisted despite upping the aspirin dose.
"This would suggest that clopidogrel might be appropriate
for some diabetics," suggests Dr Gurbel, "in addition
to a higher dose of aspirin." It seems that the antithrombotic
effects of aspirin aren't all accounted for by COX-1
inhibition.
Though preliminary, Dr Gurbel's
study suggests that screening diabetics with high risk
of heart disease for aspirin resistance needs consideration,
to determine appropriate dosing. But point-of-service
assays aren't available for certain measures, including
collagen-induced platelet aggregation, for which Dr
Gurbel detected resistance in diabetics.
"We really aren't certain whether
platelet reactivity does predict clinical outcomes,
at this point," he notes, emphasizing the causal disconnect
between clinical and physiological indices of aspirin
resistance. "Myocardial infarction is a disease of platelets,
though, and the fact that we're not sure of the right
dose of aspirin, in 2007, is mind-blowing. It could
have enormous clinical outcomes."
But neither Dr Gurbel nor Dr Retnakaran
thinks doctors should be increasing aspirin doses just
yet. "In Dr Gurbel's study," says Dr Retnakaran, "they
found physiological measures of resistance which could
be related to aspirin's lowered clinical efficacy, but
raising the dose can't be recommended at this point.
It's important to manage CVD risks aggressively in diabetics,
but it doesn't mean we've altered our practice, which
still follows the Canadian Diabetes Association [CDA]
guidelines."
CVD
RISK RAMPANT
Heart disease is an important part of managing the potential
complications of diabetes. In response to this, the
CDA has ramped up efforts to get the message out, with
a recent ad campaign that warns that four out of five
diabetics will die of heart disease. Dr Retnakaran shares
their concerns. "Cardiovascular disease is a really
important cause of morbidity and mortality in diabetes,
where there's two to four times the risk of heart disease,"
he says. "The level of risk for cardiovascular events
in diabetics without established CVD is similar to that
found in non-diabetics with established CVD. You might
say there's a cardiovascular risk equivalence between
the two."
Low-dose aspirin is a cardioprotective
mainstay, and the CDA recommends it for diabetics with
established CVD, or other CVD risk factors in addition
to diabetes. Despite this, aspirin use in diabetics
with CVD is reported to be low, in the range of 70%,
says Dr Retnakaran. It gets lower — near 20% —
in adult diabetics with risk factors but not established
CVD.
Dr Gurbel's study — which
was the first to compare dose-response effects of aspirin
on platelet aggregation between diabetics and non-diabetics
— hints that a higher recommended dosage may be
on the horizon. According to Dr Gurbel, "A one-size-fits-all
strategy doesn't make physiological sense, and I think
that patients are being harmed by a head-in-the-sand
mentality."
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