Biological efficacy of twice daily

aspirin in type 2
diabetic patients with coronary
artery disease
Jean-Guillaume Dillinger, MD, a,c Akram Drissa, MD, a,c Georgios Sideris, MD, a Claire Bal dit
Sollier, PhD, b
Sebastian Voicu, MD, a Stephane Manzo Silberman, MD, a Damien Logeart, MD, a Ludovic
Drouet, MD, PhD, b
and Patrick Henry, MD, PhD a Paris, France

Firman
Hakim Alkatiri
CARDIOLOGY AND VASCULAR DEPARTMENT
MEDICAL FACULTY OF HASANUDDIN UNIVERSITY
2012

Background
Cardiovascular disease (CVD) remains the
leading cause of morbimortality in patients
with type 2 diabetes mellitus (DM).

Guidelines recommend low dose of aspirin

in secondary prevention of CVD in patients
with DM to decrease the rate of
cardiovascular events.

 Diabetes is associated with a high rate of

events after acute coronary syndrome and
percutaneous
coronary
intervention
despite aspirin treatment.
Once daily aspirin might not provide 24hour stable biological efficacy in patients
with diabetes.

ACS + DM

Aim
To compare the biological efficacy of the
same daily dose of aspirin given either
once (OPD) or divided twice per day in a
population of selected diabetic patients
with coronary artery disease (CAD)

Methods
Single-center, crossover study enrolled all
consecutive stable patients with DM presenting to
the Department of Cardiology, Lariboisiere
Hospital, between September 2010 and March
2011.

Inclusion
DM and documented CAD and had been treated
for at least 7 days with a nonenteric-coated
aspirin.
Population with a higher risk of ALE (Aspirin lack
of efficacy) DM with at least one of the
following defined from previous study:
- Current smoking,
- Hs-CRP > 4 mg/L,
- Fibrinogen > 4 g/L,
- Platelet count > 270 103/mm3.

Exclusion
Percutaneous coronary intervention
or ACS occurring within the month
before.

Design

Study end points

To determine whether the same daily dose of aspirin given
twice per day was more effective than a single intake on
the specific pharmacodynamic effect of aspirin on platelets
as assessed by light transmission aggregometry
triggered by arachidonic acid (AA) (LTA-AA) 0.5
mg/mL.
The secondary end point of the study was the proportion
of patients with high platelet global reactivity while on
aspirin either OPD or twice per day as measured by a test
evaluating global platelet reactivity, that is, the Platelet
Function Analyzer-100 (PFA-100) with collagenepinephrine
(EPI) cartridge and adenosine diphosphate (ADP) cartridge.

RESULT

Of the criteria qualifying

patients as being at high
risk of ALE,
- 27% of patients were
current smokers,
- 46% had an hs-CRP >4
mg/L,
- 38% had fibrinogen >4
g/L, and
- 36% a platelet count
>270 103/mm3.
- 30% had 2 of these
criteria; 15%, 3; and 7%,
four.

 The PFA-100 was performed to

evaluate global reactivity on collagen
membrane of platelet sensitized with
EPI and ADP depending on the
cartridge

Discussion
Clinical and biological aspirin resistance
Aspirin resistance can be diagnosed
clinically by the occurrence of an
atherothrombotic ischemic event in a
patient taking a therapeutic dose of aspirin.
The incidence of patients not achieving an
adequate antiplatelet effect from aspirin
varies greatly from one report to another
ranging from 5% to 45%.

Possible mechanisms of ALE

Several mechanisms have been put forward to
explain aspirin resistance or low responsiveness
Which is one of the major cause of resistance in daily
clinical practice deficient aspirin absorption, and
metabolism drug interactions (as with proton pump
inhibitors or nonsteroidal anti-inflammatory drugs).
Di Minno et al. demonstrated in a small population
that dose schedules of aspirin are not effective in
patients with diabetic angiopathy probably because
these patients have a high rate of entry of new
platelets in the circulation.

Di Minno et al

 In normal conditions, approximately 10% to 15%

of circulating platelets are replaced daily, and
near normal aggregation due to nonacetylated
platelet replacement has been found 48 to 72
hours after last aspirin intake.
The recovery could be reached in <24 hours in
patients whose platelet turnover is accelerated as
for patients with DM, atherosclerotic lesions,
and/or inflammatory syndrome.

 ALE was related to DM, biological

inflammatory
markers,
and
current
smoking.
The main explication for ALE is accelerated
platelet turnover.

Conclussion
In patients with DM with elevated
inflammatory markers or smoking
(high risk of ALE), the same dose of
aspirin given twice per day is
more effective than the same
dose given OPD.

THANK
YOU