Consensus doc questions preventive use of aspirin for CV events in diabetics

Twitter icon
Facebook icon
LinkedIn icon
e-mail icon
Google icon
Diabetic patients have a two- to fourfold increased risk of experiencing cardiovascular events compared to patients without diabetes. While aspirin has been shown to reduce mortality in patients with MI or stroke, the FDA has not approved aspirin as a first-line treatment to prevent these adverse events in diabetics.

Due to scarce research on the aforementioned topics, in an American College of Cardiology Foundation (ACCF) expert consensus document published May 27 in the Journal of the American College of Cardiology, experts synthesized prior data on the topic and offered recommendations for aspirin usage.

While numerous studies have been conducted to evaluate the administration of aspirin to prevent CV events in diabetics, the experts said that most of the studies were inconclusive at best. In total, nine studies were conducted, but only three focused on the effects of aspirin on diabetic patients only, the rest included diabetics in subgroups of larger aspirin trials.

After the researchers synthesized the prior data, members concluded that the evidence still “lack[s] sufficient rigor.” They wrote that “no single trial provides definitive results.”  To advance the rather questionable data, the authors performed a meta-analysis of the nine aspirin prevention trials.

In 2007, the American Heart Association (AHA) and American Diabetes Association (ADA)  jointly issued a statement that recommended 75-162 mg of aspirin per day could be used as a primary prevention strategy in diabetic patients over 40 who were at high risk for CV risk factors. However, the FDA has still not approved this notion.

For the paper, the experts looked at the following questions in order to provide updated recommendations for aspirin use in diabetics:
  • What is the evidence regarding aspirin to prevent initial cardiovascular events in people with diabetes?
  • How can we reconcile the results of the different primary prevention trials?
  • What are the risks of aspirin and are they similar to or different for people with diabetes versus those without?
  • What do we know about the recommended dosage or dosage range?
  • How can we integrate potential benefits and risks of aspirin to determine which patients with diabetes should receive aspirin for the primary prevention of cardiovascular events?
  • What are the needs for future research?

By pooling data, researchers found that the meta-analysis outlined their previous findings--that aspirin prevention strategies showed a significant reduction in MI and stroke in diabetic patients. However, the authors still said that “there have been too few events in the available trials to precisely estimate its effects and because our findings rely on analyses of subgroups within larger trials, which have more potential for bias," beneficial evidence still is lacking.

While the experts said that aspirin may be a good source of prevention for diabetic patients, it can also cause harm, including hemorrhagic stroke at an average rate of 1 in 10,000 patients annually. In addition, results based on six of the studies showed a 54 percent increased risk for extracranial bleeding (mainly gastrointestinal).

According to the authors, a study conducted by the Antithrombotic Trialists found that CVD risk factors increased the risk for extracranial bleeding from administration of aspirin. The authors said that this could suggest that “those at higher CVD risk are also at higher risk for aspirin-related adverse effects.” The trial showed that diabetics taking aspirin had a 55 percent greater risk compared to those without diabetes who were administered aspirin.

Additionally, the paper stated that the optimal dosages of aspirin to prevent CVD events were not clearly established by the data. The effects of aspirin on the platelet are permanent, the authors wrote, even low doses of the drug can be as preventative as high doses in that high doses fail to produce significant reductions in thrombotic events.

While the authors say that overall trials show that aspirin “modestly” reduces CV risks, future research is needed to make the benefits clear.

For now, the experts have made the following recommendations:
  • For patients with no prior history of vascular disease and who are not at high risk for bleeding, a low dose—75-162 mg/day—of aspirin may be “reasonable for adults with diabetes”;
  • Aspirin is not recommended for CVD prevention for diabetic adult patients at a low risk for CVD events (men under age 50 and women under 60 with no major risk factors) “as the potential adverse effects from bleeding offset the potential benefits”; and
  • Low-dose aspirin use for prevention “might be considered for those with diabetes at intermediate CVD risk (younger patients with one of more risk factors, or older patients with no risk factors, or patients with 10-year CVD risk of 5-10 percent) until further research is available.”

According to the authors, “Whether patients have sufficient CVD risk to warrant aspirin use under these assumptions will also depend on the use of other effective techniques for CVD risk reduction, including statins, blood pressure control and smoking cessation.”

The authors wrote that if these therapies are used to lower CVD events, than fewer diabetic patients will have the need to be administered aspirin use.

The authors concluded: “While some encouraging epidemiologic and retrospective data exists for current methods of surrogate platelet testing for aspirin, these data lack sufficient rigor to inform clinical decision making, particularly in the setting of primary prevention.”

The authors said that two trials—ACCCEPT-D (Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes) and ASCEND (A Study of Cardiovascular Events in Diabetes)—will look to evaluate low-dose aspirin and its efficacy to prevent CV events in diabetic patients.