2008 Clinical Practice Guidelines - Canadian Diabetes Association

(7±8% risk reduction). Within this meta-analysis, the Early
Treatment Diabetic Retinopathy Study (ETDRS) (22) was the
only trial specifically designed to examine the effect of highdose
ASA in high-risk subjects with diabetes and retinopathy.
The reduction in serious vascular events (vascular death, nonfatal
MI, nonfatal stoke) was nonsignificant (RR 0.91, 99%
CI, 0.75–1.11), although a larger reduction (although still
nonsignificant) was noted for fatal and nonfatal MI (RR 0.83,
99% CI, 0.66–1.04).
Taken together, these studies suggest that ASA therapy may
confer less benefit for CV event reduction in individuals with
diabetes than in those without diabetes. This may be due to
increased ASA resistance in people with diabetes, as well as
ASA-insensitive mechanisms of platelet activation and thrombus
formation. Given the known benefit of ASA in secondary
prevention of vascular events in the general population (21)
and a trend toward MI reduction in people with diabetes and
CAD (22), it is reasonable to consider prescribing ASA for
people with diabetes and CAD.The decision to prescribe ASA
for primary prevention of CV events should be based on individual
clinical judgment given the lack of evidence for benefit
and the side effects of long-term use.
If an antiplatelet agent is to be used, ASA appears to be as
effective as other antiplatelet agents (20) and may be the best
choice given that it is the most widely studied and the most
economical. Patients who cannot tolerate ASA should substitute
an alternate antiplatelet agent, such as clopidogrel.
Clopidogrel is an inhibitor of adenosine diphosphate-induced
platelet aggregation that is effective for secondary prevention
in people with diabetes. In the posthoc analysis of the diabetic
subgroup (1914 patients) of the Clopidogrel Versus Aspirin
in Patients with Risk of Ischemic Events (CAPRIE) trial, the
composite vascular endpoint (ischemic stroke, MI or vascular
death) occurred in 15.6% of those randomized to daily treatment
with 75 mg clopidogrel vs. 17.7% of those on 325 mg
of ASA (p=0.42) (23). The addition of clopidogrel to lowdose
ASA was not shown to be of benefit in high-risk subjects
with diabetes in the Clopidogrel and Aspirin Versus Aspirin
Alone for the Prevention of Atherothrombotic Events
(CHARISMA) trial (24).
The effective dose of ASA in people with diabetes remains
controversial. It has been suggested that due to the increase in
platelet turnover and thromboxane synthesis in diabetes,
higher doses or multiple daily dosing of ASA may be preferred
(16). Clinical trials in subjects without diabetes suggest no
differences in daily ASA dosages in terms of reducing CV risk.
Similar results were seen in both the ETDRS and the PPP trials,
despite the use of 650 mg per day in the former and 100
mg per day in the latter.There have been no clinical trials on
whether multiple daily dosing would improve CV outcomes.
Low-dose ASA (75–325 mg daily) is often recommended to
limit both gastrointestinal (GI) toxicity and the potential
adverse effects of prostaglandin inhibition on renal function
or BP control.
ASA therapy does not increase the risk of vitreous hemorrhage
in people with diabetic retinopathy (17), nor does it
increase stroke or fatal bleeds in those with adequately controlled
hypertension (18). Antiplatelet agents should not be
used in people with inherited or acquired bleeding disorders,
recent GI bleeding or serious hepatic failure. ASA should not
be used in individuals 40 years with microalbuminuria] as follows:
• For all people with diabetes (in alphabetical order):
• Lifestyle modification
• Achievement and maintenance
of a healthy body weight
• Healthy diet
• Regular physical activity
• Smoking cessation
• Optimize BP control
• Optimize glycemic control
• For all people with diabetes considered at high risk
of a CV event (in alphabetical order):
• ACE inhibitor or ARB therapy
• Antiplatelet therapy (as recommended)
• Lipid-lowering medication (primarily statins)
2. Individuals with diabetes at high risk for CV events
should receive an ACE inhibitor or ARB at doses that
have demonstrated vascular protection [Grade A, Level
1A, for people with vascular disease (4,12); Grade B, Level
1A, for other high-risk groups (4,12)].
3. Low-dose ASA therapy (81–325 mg) may be considered
in people with stable CVD [Grade D, Consensus].
Clopidogrel (75 mg) may be considered in people
unable to tolerate ASA [Grade D, Consensus]. The decision
to prescribe antiplatelet therapy for primary prevention
of CV events, however, should be based on
individual clinical judgment [Grade D, Consensus].
OTHER RELEVANT GUIDELINES
Definition, Classification and Diagnosis of Diabetes
and Other Dysglycemic Categories, p. S10
Screening for Type 1 and Type 2 Diabetes, p. S14
Targets for Glycemic Control, p. S29
Physical Activity and Diabetes, p. S37
Nutrition Therapy, p. S40
Management of Obesity in Diabetes, p. S77
Identification of Individuals at High Risk of Coronary Events,
p. S95
Screening for the Presence of Coronary Artery Disease, p. S99
Dyslipidemia, p. S107
Treatment of Hypertension, p. S115
S105
COMPLICATIONS AND COMORBIDITIES