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Highlights from

European Society of Cardiology

Congress 2018

Munich 25-29 August 2018

ASCEND: Reduced serious vascular events offset by increased bleeds with aspirin in individuals with diabetes

Take-home messages
  • Despite reducing the risk of serious vascular events by 12%, aspirin significantly increased the risk of major bleeding by 29%
  • Aspirin did not reduce the risk of gastrointestinal or any other cancer
“We found no added benefit of these patients taking aspirin in addition to their other medications.”

Professor Jane Armitage
University of Oxford, UK

Results of a large randomised placebo-controlled trial have demonstrated that aspirin significantly reduces the risk of serious vascular events but that these clinical benefits are reduced by an increased risk of major bleeding in patients with diabetes and with no cardiovascular disease (CVD) at trial start.

Presenting the results of the ASCEND (A Study of Cardiovascular Events iN Diabetes) trial (NCT00135226) at the ESC Congress 2018 was Jane Armitage, Principal Investigator, and Professor of Clinical Trials and Epidemiology, University of Oxford, UK. Results were also published simultaneously in the New England Journal of Medicine.

In addition to assessing vascular events and bleeding, cancer incidence was monitored. “Aspirin did not reduce the risk of gastrointestinal [GI] cancers or indeed any other cancers, with large numbers of cancers reported. Notably, 1,700 participants reported cancers out of over 15,000 individuals in the trial,” reported Professor Armitage.

She added that while aspirin reduced the risk of serious vascular events it also, as expected, increased the risk of major bleeding; the latter by 29%. “We found no added benefit of these patients taking aspirin in addition to their other medications, and the absolute benefits of avoiding vascular events were counterbalanced by increased risk of bleeding,” she asserted. Furthermore, the researchers were unable to identify a subgroup where the benefits outweighed the risks.

Aspirin has long been known to reduce the risk of secondary cardiovascular (CV) events in those with established CVD. Most patients with diabetes are at increased risk of CVD but the role of aspirin in primary prevention of CVD in this population has been unclear.

In light of this, ASCEND aimed to determine whether 100 mg aspirin daily prevented a CV event, or cancer, in patients with diabetes and with no history of CVD; the study also explored whether aspirin was associated with an increased risk of bleeding or other adverse events. Trial participants were 63% men and had a mean age of 63 years. Most patients were well managed with good glycaemic control and the majority were receiving statins and/or blood pressure-lowering therapy.

In the ASCEND trial, a total of 15,480 participants were randomised to aspirin 100 mg daily or matching placebo, with participants followed up for a mean of 7.4 years. The primary efficacy outcome comprised a first serious vascular event (myocardial infarction, stroke or transient ischaemic attack, or death from any vascular cause), while the primary safety outcome was the first major bleeding event (intracranial haemorrhage, sight-threatening bleeding event in the eye, GI bleeding, or other serious bleeding). Secondary outcomes included cancer of the GI tract.

In the aspirin group, 658 (8.5%) patients experienced a serious vascular event, compared to 743 (9.6%) in the placebo group (rate ratio 0.88; P=0.01). “This shows a significant reduction in the risk of a serious vascular events,” Professor Armitage highlighted.

There were 314 (4.1%) participants with bleeds in the aspirin group, and 245 (3.2%) in the placebo group (rate ratio 1.29; P=0.003). With respect to types of major bleeds, the largest absolute difference between the two groups was with GI bleeds (0.5%) and other extracranial bleeds (0.4%).

The researchers also investigated how bleeding varied according to participants’ baseline vascular risk. “The serious vascular event rate rose with baseline vascular risk, but the rate of bleeding on placebo as well as aspirin) also increased with vascular risk, which is why the balance of risk is crucial.”

With respect to whether patients currently on aspirin for primary prevention of CVD should stop their medication, Professor Armitage said that careful consideration needed to be given to the risk of the events in the balance. “In general, there has been this feeling that vascular events—because they often can be disabling—are more important, but these are serious bleeds…we know that people do die of serious GI bleeds in particular,” she said. Professor Armitage concluded that these were important findings, with implications for millions of people with diabetes who have not experienced a CV event. “Current clinical guidelines vary in their recommendations about the use of aspirin for primary prevention because of a previous lack of clear evidence. The results of ASCEND now provide much-needed clarity.”

Based on Armitage J, et al. ASCEND - a randomized trial of aspirin versus placebo for primary cardiovascular prevention in 15,480 people with diabetes (2315). Presented Sunday, 26 August 2018.

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