Aspirin reduced the risk for myocardial infarction in patients with diabetes mellitus and diabetic retinopathy
ACP J Club. 1993 Mar-April;118:37. doi:10.7326/ACPJC-1993-118-2-037
ETDRS Investigators. Aspirin effects on mortality and morbidity in patients with diabetes mellitus. Early Treatment Diabetic Retinopathy Study Report 14. JAMA. 1992 Sep 9;268:1292-300.
To assess the effects of aspirin on all-cause and cause-specific mortality, the occurrence of cardiovascular events, and the incidence of kidney disease in patients with diabetes mellitus and diabetic retinopathy (Early Treatment Diabetic Retinopathy Study).
Randomized, double-blind, placebo-controlled, multicenter trial with a mean follow-up of 5 years.
22 clinical centers in the United States.
3711 patients (56% men) between the ages of 18 and 70 years (52% ≥ 50 y) with diabetes mellitus and diabetic retinopathy. Exclusion criteria were systolic blood pressure > 210 mm Hg or diastolic blood pressure > 110 mm Hg despite therapy; gastrointestinal hemorrhage or active gastrointestinal ulcer in the previous 2 years; inability to stop taking anticoagulants or antiplatelet drugs; allergy to aspirin; pregnancy or lactation; and poor prognosis for 5 years follow-up. Between 80% to 90% of patients completed follow-up visits after 3 years.
1856 patients received 650 mg of aspirin/d and 1855 received placebo.
Main outcome measures
All-cause and cause-specific mortality, fatal and nonfatal myocardial infarction and stroke, amputations, and kidney disease or failure.
All-cause and cardiovascular mortality were similar in the aspirin and placebo groups (18% vs 20% and 13% vs 15%, respectively). Fewer patients in the aspirin group had a myocardial infarction than patients in the control group (P <0.05) (Table). The estimate of relative risk for fatal and nonfatal myocardial infarction over the entire follow-up period using survival analysis was 0.83 (CI 0.66 to 1.04, P = 0.04), favoring aspirin therapy. The reduction in fatal and nonfatal myocardial infarction was distributed across all types of diabetes. The occurrence of fatal or nonfatal stroke showed a trend favoring placebo (13% vs 15%, P > 0.2). Amputations occurred in approximately 5% of both groups, and the occurrence of kidney disease was 12%. A 2% incidence of minor bleeding occurred in both groups. Results were similar for patients with type 1 and type 2 diabetes and for men and women.
Fatal and nonfatal myocardial infarctions were reduced in patients with diabetes mellitus and diabetic retinopathy who received aspirin. Reduction in all-cause and in cardiovascular mortality did not reach statistical significance.
Source of funding: National Eye Institute.
For article reprint: Dr. F.L. Ferris, Biometry and Epidemiology Program, National Eye Institute, Room 6A-24, 9000 Rockville Pike, Bethesda, MD 20892, USA. FAX 301-496-2297.
Table. Aspirin vs placebo to prevent myocardial infarction in patients with diabetes and diabetic retinopathy
|Outcome at 7 years||Aspirin||Placebo||RRR (95% CI)||NNT (CI)|
|Myocardial infarction||13.0%||15.3%||15% (0.3 to 27)||44 (22 to 3285)|
*Abbreviations defined in Glossary; RRR, NNT, NNH, and CI calculated from data in article.
After 5 years of follow-up, nearly 20% of the patients in this study died or had a stroke or myocardial infarction. This high event rate is not surprising because all patients had diabetes and diabetic retinopathy, nearly half of them smoked, and half had evidence of some form of cardiovascular disease. The benefits of aspirin, as measured by absolute risk reduction, were therefore more impressive than the benefits seen in studies of healthier populations (for example, American and British physicians). 29 patients with diabetes were treated for 5 years with aspirin daily to prevent 1 death, stroke, or myocardial infarction. This compares favorably with other therapeutic maneuvers; for example, 141 patients with mild hypertension need to be treated for 5 years to prevent 1 of these same outcomes.
The results of this study are consistent with the findings of a meta-analysis of the effects of antiplatelet therapy on the secondary prevention of vascular disease (1). A trend in this study, however, suggested a small increased risk for stroke from aspirin, similar to the trend seen in the studies of aspirin among American and British physicians.
Although aspirin protects against myocardial infarction, evidence does not support its prevention of diabetic nephropathy (dialysis), peripheral vascular disease (amputations), or diabetic retinopathy. Aspirin does not increase the risk for vitreous or retinal hemorrhage among these patients (2). Physicians should strongly consider low-dose (no more than 325 mg/d) aspirin for most of their diabetic patients.
Arthur T. Evans, MD, MPH
University of North CarolinaChapel Hill, North Carolina, USA