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This article originally posted 12 June, 2004 and appeared in

Clinical Rules for Management of Patients with Type 2 Diabetes

Clinical Rules for Management of Patients With
Type 2 Diabetes

ADA Issues Recommendations for Aspirin Therapy in Diabetes

Virginia Peragallo-Dittko, RN, MA, CDE
Program Director, Diabetes Education Center
Winthrop-University Hospital
Mineola, New York


The widely published literature supporting the benefits of aspirin therapy has traditionally focused on secondary prevention for persons with a previous myocardial infarction. However, questions remained concerning the benefits of aspirin therapy for people with diabetes who have a two- to fourfold increase in the risk of dying from the complications of cardiovascular disease.1 In a position statement and technical review with supporting documentation in November 1997, the American Diabetes Association issued recommendations for aspirin therapy in diabetes.1,2 Meta-analyses of studies and large-scale collaborative trials in men and women with diabetes support the view that low-dose aspirin therapy, unless contraindicated, should be prescribed as a secondary prevention strategy. In addition, substantial evidence suggests that such therapy should also be used as a primary prevention in men and women with diabetes who are at high risk for cardiovascular events.1


Close to 50% of people with type 2 diabetes have evidence of cardiovascular disease or have one or more cardiovascular risk factors at the time a diagnosis of diabetes is made. Many studies have documented that people with impaired glucose tolerance are at high risk for cardiovascular disease and often have cardiovascular risk factors other than glycemia (ie, hypertension, hyperlipidemia, insulin resistance).1 As the authors of the San Antonio Heart Study3 note, the clock for coronary heart disease probably starts ticking before the onset of clinical diabetes in many patients. Atherothrombotic macrovascular disease is the major cause of mortality in the diabetes population, and the enhanced aggregability of platelets has been studied as a possible contributor to the prothrombotic condition in patients with diabetes. Several studies have demonstrated an increased sensitivity of platelets isolated from humans with diabetes to platelet-aggregating agents in vitro. A major mechanism contributing to the hypersensitivity of platelets from patients with diabetes is the increased production of thromboxane, a potent vasoconstrictor and platelet aggregant. There is evidence of excess thromboxane release in type 2 diabetes patients with cardiovascular disease.4 Aspirin rapidly blocks thromboxane synthesis.

The value of using aspirin therapy as primary prevention was shown in the US Physiciansí Health Study, a randomized, double-blind placebo-controlled trial in adult men using low-dose aspirin (325 mg every other day).5 The largest study of aspirin prophylaxis in diabetes is the Early Treatment Diabetic Retinopathy Study (ETDRS), which included patients with either type 1 or type 2 diabetes, 48% of whom had a history of cardiovascular disease. Among those randomized to aspirin therapy, the relative risk for myocardial infarction in the first 5 years was lowered significantly.6 An important finding in the ETDRS was that there was no increased risk of retinal or vitreous bleeding, even with relatively high-dose (650 mg/day) aspirin therapy in diabetes patients with established retinopathy.

The U.S. Physicians' Health Study, a double blind study of primary prevention subjects, showed that only four percent of those who underwent aspirin therapy suffered a heart attack, compared to over 10 percent in the placebo group.

Dosage and Safety

Aspirin therapy carries the risk of gastric mucosal injury and gastrointestinal hemorrhage. However, these effects are dose related and are reduced to placebo levels when enteric-coated preparations of 75 to 325 mg/day are used.7,8 A dose as low as 75 mg of enteric-coated aspirin is just as effective as higher doses of either plain or enteric-coated aspirin in inhibiting thromboxane synthesis and, when platelet turnover is rapid, as suggested in diabetic vascular disease, the steady plasma concentration of aspirin enteric preparations theoretically allows for constant suppression of thromboxane synthesis.2 The studies cited support the efficacy of aspirin therapy in dosages of 75 mg to 325 mg/day, but the lowest dose available for over-the-counter purchase is 81 mg. Thus, in its position statement the ADA recommends use of enteric-coated aspirin in doses of 81 to 325 mg/day for people with diabetes who are older than 30 years (those under 30 years were not studied).2 People with aspirin allergy, bleeding tendency, recent gastrointestinal bleeding, and clinically active hepatic disease as well as those on anticoagulant therapy may not be candidates for aspirin therapy.


The recommendation of "an aspirin a day" has been published in the lay literature and careful emphasis has been placed on the need to consult with one’s healthcare provider before initiating therapy. Since many patients do not perceive aspirin as a medication, they begin aspirin therapy without discussing it with their providers or they do not report aspirin therapy when asked to list medications they are taking. Aspirin has the potential for harm because of the cumulative effect of aspirin-containing prescription and other over-the-counter products that may be used but not reported. Since many patients consult with different specialists, who may prescribe anticoagulants or aspirin-containing products, a comprehensive medication history is required. The table provides an abbreviated list of over-the-counter medications that contain aspirin.


An effective strategy to prevent or delay accelerated atherosclerosis or thrombosis in patients with diabetes includes aggressive treatment of diabetes and other cardiovascular risk factors. The American Diabetes Association position statement on Aspirin Therapy in Diabetes2 recommends:

1. Aspirin use as a secondary prevention strategy in men and women with diabetes who have evidence of large vessel disease. This includes patients with a history of myocardial infarction, vascular bypass procedures, stroke or transient ischemic attack, peripheral vascular disease, claudication, and/or angina.

2. In addition to treating identified primary cardiovascular risk factor(s), consideration of aspirin therapy as a primary prevention strategy in high-risk men and women with type 1 or type 2 diabetes. This includes subjects with:

  • A family history of coronary heart disease
  • Cigarette smoking
  • Hypertension
  • Obesity (>120% desirable weight); BMI >28 in women, >27.3 in men
  • Albuminuria (micro or macro)
  • Cholesterol >200 mg/dL
  • LDL cholesterol >130 mg/dL
  • HDL cholesterol <40 mg/dL
  • Triglycerides >250 mg/dL


1. Colwell JA. Aspirin therapy in diabetes (Technical Review). Diabetes Care. 1997;20:1767-1771.

2. American Diabetes Association. Aspirin therapy in diabetes (Position Statement). Diabetes Care. 1997;20:1772-1773.

3. Haffner SM, Stern MP, Hazuda HP, Mitchell BD, Patterson JK. Cardiovascular risk factors in confirmed prediabetic individuals: does the clock for coronary heart disease start ticking before the onset of clinical diabetes? JAMA. 1990;263:2893-2898.

4. Colwell JA, Jokl R. Vascular thrombosis in diabetes. In: Ellenberg and Rifkinís Diabetes Mellitus: Theory and Practice. 5th ed. Porte Jr D, Sherwin RS, eds. Connecticut: Appleton and Lange; 1997.

5. Steering Committee of the Physiciansí Health Study Research Group. Final report on the aspirin component of the ongoing Physiciansí Health Study. N Engl J Med. 1989;321:129-135.

6. ETDRS Investigators. Aspirin effects on mortality and morbidity in patients with diabetes mellitus. JAMA. 1992;268:1292-1300.

7. Patrono C, Davi G. Antiplatelet agents in the prevention of diabetic vascular complications. Diabetes Metab Rev. 1993;9:1-13.

8. Patrono C. Aspirin as an antiplatelet drug.
N Engl J Med. 1994;330:1287-1294.

9. Physiciansí Desk Reference for Nonprescription Drugs.® 18th ed. Montvale, NJ: Medical Economics Company; 1997.



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This article originally posted 12 June, 2004 and appeared in

Past five issues: Diabetes Clinical Mastery Series Issue 202 | SGLT-2 Inhibitors Special Edition August 2014 | Issue 742 | Diabetes Clinical Mastery Series Issue 201 | Humulin Insulin Special Edition August 2014 |

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