ASCEND
A Study of Cardiovascular Events iN Diabetes
Year of Publication: 2018
Authors: Louise Bowman, Marion Mafham, William Stevens, ..., The ASCEND Study Collaborative Group
Journal: American Heart Journal
Citation: Bowman L, et al. Am Heart J. 2018;198:135-144.
PDF: Clinical Question
Does daily low-dose aspirin or omega-3 fatty acid supplementation reduce the risk of cardiovascular events or cancer in patients with diabetes but no known arterial disease?
Bottom Line
In 15,480 diabetic adults without cardiovascular disease, aspirin 100 mg/day modestly reduced serious vascular events (8.5% vs 9.6%; RR 0.88; 95% CI 0.79-0.97; P=0.01) but significantly increased major bleeding (4.1% vs 3.2%; RR 1.29; 95% CI 1.09-1.52; P=0.003) over median 7.4 years. The absolute benefit (1.1% fewer vascular events) was largely offset by bleeding risk (0.9% more major bleeds). Omega-3 FA (1g/day) had no significant effect on vascular events (8.9% vs 9.2%; RR 0.97; P=0.55). 2×2 factorial, double-blind, UK-based.
Major Points
- Aspirin reduced serious vascular events: 8.5% vs 9.6% (RR 0.88; 95% CI 0.79-0.97; P=0.01) — 12% relative reduction.
- But increased major bleeding: 4.1% vs 3.2% (RR 1.29; 95% CI 1.09-1.52; P=0.003) — mostly GI and other extracranial.
- Net benefit marginal: 1.1% fewer vascular events offset by 0.9% more major bleeds.
- Omega-3 FA had no effect: 8.9% vs 9.2% (RR 0.97; 95% CI 0.87-1.08; P=0.55).
- 15,480 UK adults with diabetes, no prior arterial disease. 2×2 factorial, double-blind.
- 94% type 2 diabetes, mean age 63, 63% male, 75% on statins, 62% treated hypertension.
- Median follow-up 7.4 years. Lower event rate than expected (revised from 2% to 1.3%/year).
- Along with ASPREE and ARRIVE (2018), shifted guidelines against routine aspirin for primary prevention.
- GI tract cancer: no significant reduction with aspirin (RR 0.84; 95% CI 0.64-1.10) during treatment period.
- Funded by British Heart Foundation. Bayer provided aspirin/placebo, Mylan provided omega-3/placebo.
Design
Study Type: Randomized, double-blind, placebo-controlled, 2×2 factorial trial
Randomization: 1
Blinding: Double-blind. Centralized minimization algorithm balancing age, sex, diabetes duration, hypertension, smoking, ethnicity, cholesterol, HbA1c. 2-month placebo run-in (≥80% compliance required).
Enrollment Period: June 2005 to July 2011
Follow-up Duration: Median 7.4 years
Centers: UK-wide (mail-based recruitment)
Countries: United Kingdom
Sample Size: 15480
Analysis: Intention-to-treat. Log-rank. 2P<0.05. >90% power to detect 15% reduction in SVE.
Inclusion Criteria
- Age ≥40 years
- Diagnosis of type 1 or 2 diabetes
- No diagnosed occlusive arterial disease
- No contraindication to aspirin or omega-3 FA
- No life-threatening illness precluding long-term follow-up
Exclusion Criteria
- History of MI, stroke, angina, or TIA
- Use of anticoagulants (e.g., warfarin)
- Recent GI bleeding or active peptic ulcer
- Aspirin or omega-3 allergy
- Life expectancy <5 years
Baseline Characteristics
| Characteristic | Comorbidities | Qualifying Event |
|---|---|---|
| Hypertension | 62 | |
| Diabetes | 100 | |
| Smoker | 8 |
Arms
| Field | Aspirin Group | Control | Omega-3 FA Group | Control |
|---|---|---|---|---|
| Intervention | 100 mg aspirin daily | Placebo tablet daily | 1 g omega-3 fatty acids daily (0.41 g EPA, 0.34 g DHA) | Placebo omega-3 capsule daily |
| Duration | Median 7.4 years | Median 7.4 years | Median 7.4 years | Median 7.4 years |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Serious vascular event (non-fatal MI, non-fatal stroke, TIA, or vascular death) | Primary | 9.6% | 8.5% | 0.88 | 0.01 |
| Major bleeding | Secondary | 3.2% | 4.1% | 1.29 | <0.001 |
| GI tract cancers | Secondary | ||||
| Major Bleeding | Adverse | 3.2% | 4.1% | <0.001 | |
Subgroup Analysis
No significant heterogeneity in treatment effect across subgroups defined by age, sex, diabetes duration, or statin use
Criticisms
- No inclusion of participants outside UK limits generalizability
- Bleeding risk may offset benefit in some populations
- Cancer prevention analysis underpowered within trial duration
- 2×2 factorial design complicates isolation of effects
Funding
British Heart Foundation (BHF), Bayer AG (aspirin), Mylan (omega-3 capsules)
Based on: ASCEND (American Heart Journal, 2018)
Authors: Louise Bowman, Marion Mafham, William Stevens, ..., The ASCEND Study Collaborative Group
Citation: Bowman L, et al. Am Heart J. 2018;198:135-144.
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