This Physician’s Weekly feature covering guidelines for heart health in diabetes was completed in cooperation with the experts at the American Diabetes Association.

Research has shown that patients with diabetes are at two to four times greater risk of suffering cardiovascular disease (CVD) events when compared with patients who do not have diabetes. Several mechanisms have been linked to the increased CVD risk in people with diabetes, including increased intracoronary thrombus formation, elevated platelet reactivity, and worsened endothelial dysfunction. “Aspirin has been shown to be effective in reducing cardiovascular morbidity and mortality in high-risk patients with heart attack or stroke,” explains Craig D. Williams, PharmD. “However, there has been some confusion surrounding the use of aspirin in patients who do not yet have CVD. That confusion is even greater among patients with diabetes.”

In 2007, the American Diabetes Association and the American Heart Association (AHA) jointly recommended that aspirin be used as a primary prevention strategy in patients with diabetes who are at increased cardiovascular risk. This patient group includes those who are older than 40 or who have additional risk factors, such as a family history of CVD, hypertension, smoking, dyslipidemia, or albuminuria. “These recommendations were derived from older trials that included fewer patients with diabetes,” says Dr. Williams. “We now have results from two recent randomized controlled trials—the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes and the Prevention of Progression of Arterial Disease and Diabetes trials—in which aspirin use was examined specifically in patients with diabetes. These studies provide important insights on the efficacy of aspirin for primary prevention in diabetes, but they have also stirred some controversy because findings were somewhat conflicting with previous recommendations.”

Updating Recommendations

In light of new data, the American Diabetes Association, AHA, and the American College of Cardiology Foundation convened a group of experts to review and synthesize available evidence to update recommendations about the efficacy of aspirin for primary prevention in people with diabetes. Published jointly in the Journal of the American College of Cardiology, Diabetes Care, and Circulation in 2010, the new recommendations continue to strongly recommend low-dose aspirin for all patients who have previously had a heart attack or stroke. The update also indicates that low-dose aspirin therapy is a reasonable measure to prevent a first heart attack or stroke among people with diabetes who also have a high risk for CVD (Table 1).

Dr. Williams, who was a co-author of the guideline, notes that a key change from previous recommendations is the age at which patients with diabetes should receive low-dose aspirin as primary prevention. “People with diabetes who are eligible for low-dose aspirin therapy generally include most men over the age of 50 and most women over the age of 60 who have at least one additional risk factor,” he says. “Trials to determine whether aspirin can prevent a first heart attack or stroke in adults with diabetes have had mixed results. Overall, however, they suggest that aspirin modestly reduces the risk of CVD events.”

Another key update to the guideline is that some patients with diabetes are now not recommended to receive aspirin. “Low-risk patients—those who have a 10-year risk of a heart attack or stroke of less than 5%—should not receive low-dose aspirin therapy because their risks for bleeding likely outweigh any benefit,” Dr. Williams says. “The major adverse effects of aspirin therapy include intracranial and gastrointestinal bleeding. For low-risk patients, the potential benefits of aspirin are less likely than the potential harm brought on by increased bleeding rates.” The guideline also notes that scientific evidence to support aspirin therapy depends on underlying CVD risk. Patients with higher risk are expected to have greater benefits by taking aspirin, but the decision to use this therapy depends on the use of other treatments, including cholesterol-lowering agents, blood pressure control, and smoking cessation (Table 2).

Looking Ahead

The guideline notes that more research is needed to better define the specific effects of aspirin in patients with diabetes, including gender-specific differences. “We’re eagerly anticipating the result of other larger ongoing clinical trials on the use of aspirin specifically in patients with diabetes,” says Dr. Williams. “In addition, the development of an effective surrogate test for analyzing antiplatelet function—similar to what is currently available to assess A1C, blood pressure, and cholesterol—is paramount to gaining a more meaningful understanding of the efficacy of antiplatelet therapy in patients with diabetes. The hope is that more data on aspirin use in patients with diabetes and progress toward the development of antiplatelet function testing will provide clinicians with more clarity and direction on how to manage patients optimally based on their unique characteristics.”

References

Pignone M, Alberts MJ, Colwell JA, et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation. Diabetes Care, 2010;33:1395-1402. Available at: http://care.diabetesjournals.org/content/33/6/1395.extract.

Natarajan A, Zaman AG, Marshall SM. Platelet hyperactivity in type 2 diabetes: role of antiplatelet agents. Diabetes Vasc Dis Res. 2008;5:138-144.

Antithrombotic Trialists’ (ATT) Collaboration, Baigent C, Blackwell L, Collins R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849-1860.

Wolff T, Miller T, Ko S. Aspirin for the primary prevention of cardiovascular events: an update of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;150:405-410.

Buse JB, Ginsberg HN, Bakris GL, et al. American Heart Association, American Diabetes Association. Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care. 2007;30:162-172.