By Abdul Sattar Sohrani
Previous guidelines recommended low-dose aspirin therapy for the primary prevention of stroke in patients with type 1 or type 2 diabetes mellitus who were at increased cardiovascular (CV) risk. Risk factors included patient age older than 40 years, a family history of CV disease, hypertension, smoking, dyslipidemia, or albuminuria. Aspirin therapy was not recommended for patients younger than 30 years of age because no benefit had been demonstrated, and aspirin was contraindicated in patients under 21 years of age because of associated risk for Reye syndrome.
Since the Antithrombotic Trialists’ Collaboration (ATT-C) published their first meta-analysis results in May 2009, questioning the value of low-dose aspirin for primary prevention, confusion has been expressed about when to recommend aspirin for patients with diabetes. The ATT-C performed a meta-analysis of 6 primary prevention trials, including 95,000 individuals with low-average CV risk and 16 secondary prevention trials with 17,000 individuals who had high CV risk. This analysis showed that primary prevention of vascular events with aspirin is of uncertain value, whereas the risk for major episodes of hemorrhage may increase.
The ATT-C updated their recommendations for aspirin in primary prevention after considering the results from the POPADAD (Prevention of Progression of Arterial Disease and Diabetes), JPAD (Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes), and AAA (Aspirin for Asymptomatic Atherosclerosis) trials. They concluded that the benefit of aspirin appeared to outweigh its risks when used for secondary, but not primary, prevention.
De Berardis and colleagues conducted a second meta-analysis of 6 studies with 10,117 participants, which suggested that the benefit of aspirin in the primary prevention of major CV events or death in people with diabetes may be lower than in other high-risk populations. Evidence demonstrating that low-dose aspirin is beneficial was lacking in this analysis, and the benefits were not found to exceed the risk for major bleeding, particularly in patients at low CV risk (< 20% over 10 years) and in older patients (> 70 years of age) at high risk of bleeding.
These recent findings have prompted an evaluation of the current guidelines for aspirin use in primary prevention. The American Diabetes Association (ADA) Standard of Medical Care in Diabetes–2010 guidelines have backed off slightly on recommending aspirin use. The guidelines now recommend the consideration of aspirin therapy 75-162 mg daily as a primary prevention strategy for patients with type 1 or type 2 diabetes mellitus who are at increased CV risk (10-year risk > 10%).
Aspirin should not be recommended for patients at low CV risk, including women younger than 60 years of age, men younger than 50 years of age with no major risk factors, and patients with 10-year CV risk < 5%, because the low benefit is offset by the risk for significant bleeding.
Clinical judgment should be used for patients at intermediate risk or older patients with no risk factors. This generally includes most men older than 50 years of age or women older than 60 years of age who have at least 1 additional major risk factor, such as family history of CV disease, hypertension, smoking, dyslipidemia, or albuminuria. To determine risk factors, 2 assessment tools may be used: the Atherosclerosis Risk in Communities (ARIC) Risk Calculator or the ADA’s Risk Assessment Tool, Diabetes Personal Health Decisions.
In summary, it remains questionable how much benefit or risk aspirin confers for primary prevention in patients with diabetes. Currently, 2 trials are under way to answer key questions about the risk/benefit ratio: ASCEND (A Study of Cardiovascular Events in Diabetes) and ACCEPT-D (Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes). These are large, ongoing studies that will enroll up to 15,000 participants with anticipated completion dates of 2011 and 2013, respectively.
Until results from these studies are in, providers should use clinical judgment, including known approaches, to minimize CV risk, such as smoking cessation, statins, angiotensin-converting enzyme inhibitors, and the achievement of good glucose control before considering aspirin for primary prevention.