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ASCEND

A Study of Cardiovascular Events iN Diabetes

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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.

Link: https://doi.org/10.1016/j.ahj.2017.12.006

PDF: https://solaci.org/_files/esc-2018/ASCEND.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%	1.29	<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.

Content summarized and formatted by NeuroTrials.ai.

ASCEND

(2018)

Objective

Evaluate whether aspirin reduces the risk of serious vascular events in diabetic patients without known cardiovascular disease.

Study Summary

• Aspirin reduced serious vascular events by 12% but increased major bleeding by 29%. • The absolute benefits and harms were similar, resulting in no clear net benefit.

Intervention

Randomized, double-blind, placebo-controlled, 2x2 factorial trial. Patients with diabetes but no prior occlusive vascular disease were assigned to: (1) aspirin 100 mg daily vs. placebo, and (2) omega-3 fatty acids 1 g daily vs. placebo. Median follow-up: 7.4 years.

Study Design

Arms: Array

Outcome

• Serious vascular events: 8.5% (aspirin) vs. 9.6% (placebo); RR 0.88; p=0.01 • Major bleeding: 4.1% (aspirin) vs. 3.2% (placebo); RR 1.29; p=0.003 • No significant reduction in cancer or all-cause mortality • Omega-3 supplementation did not significantly reduce vascular events or cancer risk

Bottom Line

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.

Study Design

Study Type: Randomized, double-blind, placebo-controlled, 2×2 factorial trial
Randomization: Yes
Blinding: Double-blind. Centralized minimization algorithm balancing age, sex, diabetes duration, hypertension, smoking, ethnicity, cholesterol, HbA1c. 2-month placebo run-in (≥80% compliance required).
Sample Size: 15480
Follow-up: Median 7.4 years
Centers: UK-wide (mail-based recruitment)
Countries: United Kingdom

Primary Outcome

Definition: Serious vascular event (non-fatal MI, non-fatal stroke, TIA, or vascular death)

Control	Intervention	HR/OR	P-value
9.6%	8.5%	0.88 (0.79–0.97)	0.01

Limitations & 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

Citation

Bowman L, et al. Am Heart J. 2018;198:135-144.

View Original Publication →

ASCEND

A Study of Cardiovascular Events iN Diabetes

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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