A Study of Cardiovascular Events in Diabetes - ASCEND Aspirin

Mar 13, 2024
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC; Kim A. Eagle, MD, MACC
Summary Supplemental Reviewer:
Dharam J. Kumbhani, MD, SM, FACC
Trial Sponsor:
British Heart Foundation
Date Presented:
08/26/2022
Date Published:
02/22/2024
Date Updated:
03/13/2024
Original Posted Date:
08/26/2018
References

Contribution To Literature:

Highlighted text has been updated as of March 13, 2024.

The ASCEND Aspirin trial showed that the absolute reduction in cardiovascular events from aspirin was offset by a similar absolute increase in major bleeding.

Description:

The goal of the trial was to evaluate aspirin compared with placebo among diabetics with no known cardiovascular disease (CVD).

Study Design

  • Randomized
  • Parallel
  • Factorial

Patients with diabetes and no known CVD were randomized to aspirin 100 mg daily (n = 7,740) versus placebo (n = 7,740).

  • Total number of enrollees: 15,480
  • Duration of follow-up: mean 7.4 years
  • Mean patient age: 63 years
  • Percentage female: 37%

Inclusion criteria:

  • Diabetic patients ≥40 years of age without known CVD

Exclusion criteria:

  • Clear indication or contraindication to aspirin

Principal Findings:

The primary efficacy outcome, major adverse cardiovascular events (vascular death, myocardial infarction, or stroke/transient ischemic attack), occurred in 8.5% of the aspirin group compared with 9.6% of the placebo group (p = 0.01).

The primary safety outcome, major bleeding (intracranial hemorrhage, gastrointestinal [GI] hemorrhage, or sight-threatening eye bleeding), occurred in 4.1% of the aspirin group compared with 3.2% of the placebo group (p = 0.003).

The reduction in adverse events or increase in bleeding events was similar among different categories of baseline risk.

Secondary outcomes:

  • Nonfatal myocardial infarction: 2.5% with aspirin vs. 2.5% with placebo (p = not significant [NS])
  • Intracranial hemorrhage: 0.7% with aspirin vs. 0.6% with placebo (p = NS)
  • GI hemorrhage: 1.8% with aspirin vs. 1.3% with placebo (p < 0.05)
  • GI cancer: 2.0% with aspirin vs. 2.0% with placebo (p = NS)

Effects of aspirin on dementia:

  • Broad definition of dementia: 7.1% with aspirin vs. 7.8% with placebo (p = NS)
  • Narrow definition of dementia: 3.3% with aspirin vs. 3.7% with placebo (p = NS)

Effect on heart failure (HF):

  • Aspirin vs. placebo: Primary HF outcome (hospitalization or death from HF): 3.4% vs. 3.4% (p = 0.85)
  • Omega-3 fatty acid vs. placebo: Primary HF outcome (hospitalization or death from HF): 3.2% vs. 3.6% (p = 0.15); hospitalization for HF: 2.9% vs. 3.4% (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.73-1.04)

Thromboxane and future events:

  • Thromboxane A2 is released by activated platelets and has an important role in atherothrombosis. Urinary thromboxane B2 is a stable metabolite, which reflects whole-body thromboxane biosynthesis.
  • Increased levels of thromboxane B2 at baseline were associated with serious vascular events and revascularizations (HR 1.09, 95% CI 1.00-1.18), and major bleeds (HR 1.16, 95% CI 1.01-1.34), but not any cancer (HR 1.06, 95% CI 0.98-1.14).

Interpretation:

Among diabetic patients with no known CVD, aspirin was associated with a 12% relative reduction in major adverse cardiovascular events compared with placebo. Aspirin was associated with a 29% relative increase in major bleeding events compared with placebo. The increase in bleeding was mainly due to GI hemorrhage. The absolute risk reduction for major adverse cardiovascular events was 1.1%, while the absolute risk increase for major bleeding was 0.9%. There was no reduction in GI cancer, HF events, or dementia from the use of aspirin. The use of aspirin among diabetics with no known CVD needs to be individualized. Baseline levels of urinary thromboxane B2 levels were weakly associated with future serious vascular events and revascularizations, and major bleeds. There was also no effect of omega-3 fatty acid on HF events.

References:

Petrucci G, Buck GA, Rocca B, et al., on behalf of the ASCEND Study Collaborative Group. Thromboxane biosynthesis and future events in diabetes: the ASCEND trial. Eur Heart J 2024;Feb 22:[Epub ahead of print].

Presented by Dr. Michelle Goonasekera at the European Society of Cardiology Congress (ESC 2022), Barcelona, Spain, August 26, 2022.

Parish S, Mafham M, Offer A, et al., on behalf of the ASCEND Study Collaborative Group. Effects of aspirin on dementia and cognitive function in diabetic patients: the ASCEND trial. Eur Heart J 2022;43:2010-9.

Editorial: Kristensen SD, Olesen KK, Maeng M. The end of aspirin for dementia prevention in diabetes? Eur Heart J 2022;43:2020-2.

Presented by Dr. Jane M. Armitage at the American Heart Association Virtual Annual Scientific Sessions (AHA 2021), November 15, 2021.

The ASCEND Study Collaborative Group. Effects of Aspirin for Primary Prevention in Persons With Diabetes Mellitus. N Engl J Med 2018;379:1529-39.

Editorial: Ridker PM. Should Aspirin Be Used for Primary Prevention in the Post-Statin Era? N Engl J Med 2018;379:1572-4.

Presented by Dr. Jane Armitage at the European Society of Cardiology Congress, Munich, Germany, August 26, 2018.

Clinical Topics: Anticoagulation Management

Keywords: AHA21, Anticoagulants, Aspirin, Diabetes Mellitus, ESC22, ESC18


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