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Diabetes guidelines

7. Aspirin Therapy in Diabetes

People with diabetes have a two-to fourfold increase in the risk of dying from the complications of cardiovascular disease. Both men and women are at increased risk. Atherosclerosis and vascular thrombosis are major contributors, and it is generally accepted that platelets are contributory. Platelets from men and women with diabetes are often hypersensitive in vitro to platelet aggregating agents. A major mechanism is increased production of thromboxane, a potent vasoconstrictor and platelet aggregant. Investigators have found evidence in vivo of excess thromboxane release in type 2 diabetic patients with cardiovascular disease. Aspirin blocks thromboxane synthesis by acetylating platelet cyclo-oxygenase and has been used as a primary and secondary strategy to prevent cardiovascular events in non-diabetic and diabetic individuals. Meta-analyses of these studies and large-scale collaborative trials in men and women with diabetes support the view that low-dose aspirin therapy should be prescribed as a secondary prevention strategy, if no contraindications exist. Substantial evidence suggests that low-dose aspirin therapy should also be used as a primary prevention strategy in men and women with diabetes who are at high risk for cardiovascular events although no randomised trial data exist.

Efficacy

Secondary prevention trials – The Hypertension Optimal Treatment (HOT) Trial examined the effects of 75mg/day of aspirin vs. placebo in 18,790 hypertensive patients who were randomised to achieve diastolic blood pressure goals of 90, 85, or 80mmHg. There were 1,501 diabetic subjects in this trial. Aspirin significantly reduced cardiovascular events by 15% and myocardial infarction by 36%. The relative effects of aspirin were similar in non-diabetic and diabetic subjects. Fatal bleeding episodes including intracerebral bleeding were equal in the aspirin and placebo groups, while nonfatal minor bleeding episodes were more common in the aspirin group. This study provides evidence for the efficacy and safety of aspirin therapy in diabetic patients with well-controlled hypertension.

Primary prevention trials – The US Physicians' Health Study was a primary prevention trial in which a low-dose aspirin regimen (325mg every other day) was compared with placebo in male physicians. There was a 44 percent risk reduction in the treated group, and subgroup analyses in the diabetic physicians revealed a reduction in myocardial infarction from 10.1% (placebo) to 4.0% (aspirin), yielding a relative risk of 0.39 for the diabetic men on aspirin therapy.

Safety – A major risk of aspirin therapy is gastric mucosal injury and gastrointestinal haemorrhage. These effects are dose related and are reduced to placebo levels when preparations of 75-325mg are used once daily. Minor bleeding episodes (epistaxis, bruising, etc.) may occur at low doses, probably from the effect of aspirin to inhibit the platelet release reaction. In several prospective studies, a trend for an increase in hemorrhagic stroke has been seen, but has not reached statistical significance. Contraindications to aspirin therapy include allergy, bleeding tendency, anticoagulant therapy, recent gastrointestinal bleeding, and clinically active hepatic disease. Aspirin therapy is not associated with an increased risk for retinal or vitreous haemorrhage.

Dosage – The platelet release reaction is exquisitely sensitive to inhibition by aspirin. In this regard, it has been shown that 75mg of aspirin is just as effective as higher doses of either plain or enteric-coated aspirin in inhibiting thromboxane synthesis. When platelet turnover is rapid, as may be the case with diabetic vascular disease, the steady plasma aspirin concentration from enteric preparations theoretically allows for constant suppression of thromboxane synthesis. No evidence exists that combinations of aspirin with other anti-platelet drugs are any more effective than aspirin alone. Although data are limited in diabetic subjects, agents such as clopidogrel may be considered as a substitute in the case of aspirin allergy.

Recommendations

Use aspirin therapy as a secondary prevention strategy in diabetic men and women who have evidence of large vessel disease. This includes diabetic men and women with a history of myocardial infarction, vascular bypass procedure, stroke or transient ischemic attack, peripheral vascular disease, claudication, and/or angina.
In addition to treating the primary cardiovascular risk factor(s) identified, consider aspirin therapy as a primary prevention strategy in high-risk men and women with type 1 or type 2 diabetes. This includes diabetic subjects with the following:

Family history of coronary heart disease
Cigarette smoking
Hypertension
Obesity (>120% desirable weight); BMI >27.3 in women, >27.8 in men
Albuminuria (micro or macro)
Dyslipidaemia (Total Cholesterol >5.0mmol/L; LDL cholesterol >3.0mmol/L; HDL cholesterol <0.9mmol/L)

Use aspirin in doses of 75mg/day.
People with aspirin allergy, bleeding tendency, anticoagulant therapy, recent gastrointestinal bleeding, and clinically active hepatic disease are not candidates for aspirin therapy.
Aspirin therapy should not be recommended for patients under the age of 21 years because of the increased risk of Reye's syndrome associated with aspirin use in this population.

page last reviewed: 11 June 2008