News | Antiplatelet and Anticoagulation Therapies | September 05, 2018

Bleeds and Benefit With Aspirin Balanced in Diabetes Patients

ASCEND study shows aspirin does prevent serious cardiovascular events, but risk of major bleeds, lack of effect on cancer leaves role uncertain

Bleeds and Benefit With Aspirin Balanced in Diabetes Patients

September 5, 2018 — Aspirin prevented serious vascular events in patients with diabetes who did not already have cardiovascular disease, but it caused almost as many major bleeds and there was no effect on cancers. These are the late-breaking findings presented in a Hot Line Session at the European Society of Cardiology (ESC) Congress 2018, Aug. 25-28 in Munich, Germany, and published in the New England Journal of Medicine.1

Patients with diabetes are, on average, at increased risk of cardiovascular disease. Aspirin reduces the risk of second cardiovascular events and is recommended for patients who have evidence of cardiovascular disease. However, its role in preventing first events (primary prevention) is less clear because of the increase in bleeding. It has therefore been unclear whether aspirin should be recommended for cardiovascular prevention in diabetic patients without existing cardiovascular disease.2

Prof. Jane Armitage, principal investigator, Nuffield Department of Population Health, University of Oxford, U.K., said, “Even though we showed clearly that aspirin reduces the risk of vascular events, including heart attacks, strokes and mini-strokes, it also increased the risk of major bleeds, mainly from the gastrointestinal tract, so overall there was no clear benefit. It had been suggested that low-dose aspirin might protect against cancer, but we saw no reduction in any cancers; we are continuing to follow the participants to see whether any benefits appear later.”

The ASCEND trial (A Study of Cardiovascular Events iN Diabetes)3 examined whether aspirin reduced the risk of a first cardiovascular event in patients with diabetes. Between 2005 and 2011, 15,480 patients with diabetes but no history of cardiovascular disease were randomly assigned to aspirin (100 mg daily) or matching placebo.

Serious health outcomes that occurred to participants during follow-up were then recorded, including in particular:

  • First serious vascular event (the primary efficacy endpoint), which included non-fatal heart attacks, non-fatal strokes or transient ischaemic attacks (sometimes called “mini-strokes”), or death from a cardiovascular cause (but excluding any intracranial haemorrhage; i.e. bleeding in the head or brain); and
  • First major bleed (the primary safety endpoint), which included bleeding in the head or brain, from the gut or from elsewhere in the body that was serious enough to result in hospitalisation or be fatal.

During an average of 7.4 years of follow-up, a first serious vascular event occurred in 685 (8.5 percent) participants allocated aspirin and 743 (9.6 percent) allocated placebo. This meant 11 of every 1,000 participants avoided a serious vascular event during the trial as a result of allocation to aspirin. This represented a 12 percent (95 percent confidence interval [CI] 3–21 percent, p=0.01) proportional reduction in the risk of serious vascular events.

However, a first major bleed occurred in 314 (4.1 percent) participants allocated aspirin and 245 (3.2 percent) participants allocated placebo. This meant that 9 of every 1,000 participants suffered a first major bleed during the trial as a result of allocation to aspirin. This represented a 29 percent (95 percent CI 9–52 percent, p=0.003) proportional increase in the risk of major bleeding.

Consequently, overall, the numbers of participants who avoided a serious vascular event were counterbalanced by the numbers who suffered a major bleed. Even among the participants in the trial at highest vascular risk (over 2 percent per year), there were similar numbers of serious vascular events avoided as major bleeds caused. It was not possible to identify a group of patients in the trial in whom the benefits clearly outweighed the risks.

Previous studies had suggested that aspirin might produce a reduction in cancers in the gut (especially in the bowel), with the effects increasing over time. A large number of cancers were observed during 7.4 years of follow-up in the ASCEND trial. However, no effect of aspirin on incident gastrointestinal cancer was observed: 157 (2 percent) participants allocated aspirin and 158 (2 percent) participants allocated placebo (p=0.95) reported these cancers. Nor was there any apparent effect of aspirin on the overall risk of cancer (11.6 percent of those allocated aspirin versus 11.5 percent of those allocated placebo; p=0.81). Longer-term follow-up is ongoing to see if any effects on cancer emerge later.

Armitage said, “We have shown conclusively in ASCEND that aspirin reduces the risk of vascular events in primary prevention, as it does in people who already have cardiovascular disease, but these benefits are counterbalanced by the number of major bleeds caused by aspirin. This is an important finding with implications for many millions of people who have diabetes but have not yet had cardiovascular events. 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.”

“The trial participants were well-managed both for their diabetes and their cardiovascular risk,” she added. “Most participants were taking proven safe treatments, such as statins and blood pressure reducing medicines which will be protecting them from heart attacks and strokes. For them, we have shown that there is no added benefit of taking aspirin.”

For more information: www.nejm.org

References

1. The ASCEND Study Collaborative Group. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. New England Journal of Medicine, Aug. 26, 2018. DOI: 10.1056/NEJMoa1804988

2. Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2016;37:2315–2381.

3. ASCEND Study Collaborative Group. ASCEND: Characteristics of a randomized trial of aspirin and of omega-3 fatty acid supplementation in 15,480 people with diabetes. Am Heart J. 2018;198:135–144.

Related Content

Fragmin (dalteparin sodium) injection was cleared by the FDA for use in pediatric patients. It was initially approved by the FDA in 1994 for adults and is a type of heparin.

Fragmin (dalteparin sodium) injection is now cleared by the FDA for use in pediatric patients. It was initially approved by the FDA in 1994 for adults and is a type of heparin.

Technology | Antiplatelet and Anticoagulation Therapies | May 17, 2019
May 17, 2019 — The U.S.
PhaseBio Receives FDA Breakthrough Therapy Designation for Ticagrelor Reversal Agent
Technology | Antiplatelet and Anticoagulation Therapies | April 30, 2019
PhaseBio Pharmaceuticals Inc. announced the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy...
People With Heart Disease at Risk When Pharmacies Close
News | Antiplatelet and Anticoagulation Therapies | April 24, 2019
April 24, 2019 — New research from the University of Illinois at Chicago shows that when pharmacies close, people sto
Study Finds Only Six Percent of Patients Taking Statins as Directed
News | Antiplatelet and Anticoagulation Therapies | April 18, 2019
A recent study found patients with atherosclerotic cardiovascular disease cut their risk of a second major adverse...
HonorHealth Research Institute Launches SynIVUS-DAPT Study
News | Antiplatelet and Anticoagulation Therapies | April 16, 2019
HonorHealth Research Institute announced the first patients have been enrolled in the SynIVUS-DAPT Study. The clinical...
Lack of Physician Guidance, Fear of Side Effects Influence Statin Compliance
News | Antiplatelet and Anticoagulation Therapies | April 15, 2019
Despite national guidelines indicating statins can lower risk of heart attack and stroke, many patients who could...
Stopping DAPT After One Month Improved Outcomes in Stent Patients
News | Antiplatelet and Anticoagulation Therapies | March 25, 2019
Patients who stopped taking aspirin one month after receiving a stent in the heart’s arteries but continued taking the...
Apixaban Effective in Specific Cohort of Non-Valvular Atrial Fibrillation Patients
News | Antiplatelet and Anticoagulation Therapies | March 19, 2019
The Bristol-Myers Squibb-Pfizer Alliance announced results from the Phase 4 AUGUSTUS trial evaluating Eliquis (apixaban...
Researchers Develop Reversible, Drug-Free Antiplatelet Therapy
News | Antiplatelet and Anticoagulation Therapies | February 19, 2019
A new reversible, drug-free antiplatelet therapy could reduce the risk of blood clots and potentially prevent cancer...
FDA Approves Portola Pharmaceuticals' Prior Approval Supplement for Andexxa Generation 2 Manufacturing Process
News | Antiplatelet and Anticoagulation Therapies | January 02, 2019
The U.S. Food and Drug Administration (FDA) has approved Portola Pharmaceuticals’ Prior Approval Supplement (PAS) for...
Overlay Init