COMMENTARY

Aspirin for Primary Prevention in People With Diabetes: Lessons From ASCEND

Interviewer: John M. Mandrola, MD; Interviewee: Jane M. Armitage, MBBS, FRCP, FFPH

Disclosures

September 04, 2018

Editor's Note: This video was recorded outside a busy convention center. The audio quality is variable and there is some background noise.

John M. Mandrola, MD: Hi. This is John Mandrola from theheart.org | Medscape Cardiology, and I'm here at the European Society of Cardiology meeting in Munich. I'm pleased to have Prof Jane Armitage with me here today. She's from Oxford University and she presented the ASCEND trial, which is also published in the New England Journal of Medicine.[1] It was a study of the use of aspirin primary prevention in patients with diabetes.

Welcome, Professor. Can you tell us about the topline results?

Jane M. Armitage, MBBS, FRCP, FFPH: For aspirin, in this population of patients who didn't have vascular disease at the time they entered the study, we found that although the vascular events were reduced with aspirin, the benefits were counterbalanced by the increase of bleeding. We didn't see any net benefit for taking aspirin.

Mandrola: Let's start with the benefits. What were those?

Armitage: We prespecified our primary efficacy outcome as a composite of nonfatal myocardial infarction, nonfatal ischemic stroke or transient ischemic attack, and cardiovascular death. That composite is reduced by about 12% with about a 1.1% absolute benefit. But we also prespecified a bleeding outcome, which was a composite of any bleeding inside the head, any gastrointestinal (GI) bleeding and other major bleeding, and also bleeding in the eye, which would be sight-threatening. We saw a significant 29% increased risk for major bleeding, with about a 0.8% absolute hazard. What we're balancing is a small benefit against a small hazard, and although the benefit slightly wins, it's pretty marginal.

Mandrola: When I first looked at this, I thought, why more aspirin trials? Don't we have a lot of aspirin trials? Why is this a big deal?

Armitage: This is a big deal because for many years we've had trials in very low-risk individuals (healthy individuals) and trials in secondary prevention. Our trial aimed to get at the population in the middle, the intermediate-risk [patients]. But actually, because diabetes is so well managed nowadays, our population was much lower-risk than we initially thought it would be; they're probably at the low end of intermediate risk.

Mandrola: That was similar to what happened in the ARRIVE study,[2] where you expected more events than actually occurred. What do you make of that?

Armitage: I think it's good news for patients with diabetes because what it reflects is that the drugs that they're taking are protecting them: Three quarters were on statins, the vast majority were on blood pressure–lowering tablets, there were very few smokers, and their blood glucose was well controlled. Those four things were protecting these patients—probably a much safer way of keeping them well than taking an aspirin.

Mandrola: I'm so intrigued by this recent paper suggesting a possible heterogeneous effect of aspirin, in that low-dose is more beneficial for smaller people [weighing < 70 kg].[3] What do you think?

Armitage: It's a post-hoc subgroup analysis not supported by ASCEND. Our data go in the absolute opposite direction, such that most of the people in ASCEND were actually over 70 kg. They were an overweight diabetic population, and all of the benefit was seen among the people who are actually over 70 kg.

Mandrola: We should be cautious about this whole dose-targeting business.

Armitage: Absolutely.

Mandrola: I also want to ask you about aspirin and cancer prevention.

Armitage: Again, that's been based on looking at older trials with long-term follow-up, with a suggestion that there might be effects on all cancer but particularly GI tract cancers, with particular emphasis on colorectal cancer. We saw about 300 GI tract cancers, and there was absolutely no difference between the aspirin and placebo groups, but we probably didn't have enough power for that particular outcome. There's no suggestion that there's benefit emerging with longer follow-up for all cancers; we had a very similar number in the two groups (about 1700 cancers in all).

Mandrola: I'm curious about what you think: Is there any good biological effect for aspirin to prevent cancer?

Armitage: There is. If you go to meetings as I do, sometimes where there are eminent people who understand the cell biology better than I do, they do believe that there may be good biological reasons why aspirin might protect, so I don't think we can write off the possibility. But ASCEND was a good test of the overall hypothesis of aspirin for total cancer prevention, and we really didn't see any suggestion of benefit.

Mandrola: Final question. Let's say that I'm a 55-year-old with diabetes and high blood pressure and I ask you, "Should I take aspirin?"

Armitage: I'd say, make sure you take your statins and your blood pressure–lowering tablets, and keep your glucose under control and not smoke. Then, I think that the benefits of aspirin will not outweigh the risks and that you might cause yourself a nasty bleed.

Mandrola: Excellent. Thank you so much for being with us today.

Armitage: My pleasure.

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