What were the findings of the PREVENT trial?

PREVENT Trial Findings

The PREVENT trial showed that low-dose aspirin did not reduce cardiovascular events in patients with type 2 diabetes mellitus in a primary prevention setting but increased the risk of gastrointestinal bleeding.

Study Design and Population

The PREVENT trial (also known as JPAD - Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes) was a randomized controlled trial that examined whether low-dose aspirin affected cardiovascular events in Japanese patients with type 2 diabetes without pre-existing cardiovascular disease 1. The study:

• Enrolled 2,539 Japanese patients with type 2 diabetes mellitus
• Randomized participants to receive either 81-100 mg aspirin daily or no aspirin
• Had a median follow-up period of 10.3 years
• Retained 85% of patients in their original allocation groups

Primary Results

The long-term follow-up of the PREVENT/JPAD trial found:

• No reduction in cardiovascular events with low-dose aspirin (hazard ratio 1.14; 95% CI 0.91-1.42)
• Multivariable analysis adjusted for various factors showed similar results (hazard ratio 1.04; 95% CI 0.83-1.30)
• No heterogeneity of efficacy in subgroup analyses
• Sensitivity analyses on the intention-to-treat cohort yielded consistent results (hazard ratio 1.01; 95% CI 0.82-1.25)

Safety Outcomes

The trial identified important safety concerns:

• Gastrointestinal bleeding occurred in 2% of patients in the aspirin group versus 0.9% in the no-aspirin group (P=0.03)
• No significant difference in hemorrhagic stroke between groups

Context Within Broader Evidence

The PREVENT/JPAD findings align with other studies showing limited benefit of aspirin for primary prevention in diabetes:

• The ASCEND trial showed a modest 12% reduction in vascular events but a 29% increase in major bleeding with aspirin 2
• The PPP trial showed a non-significant reduction in cardiovascular events (RR 0.90,95% CI 0.50-1.62) in diabetic patients 3

Clinical Implications

These findings have important implications for clinical practice:

1. Low-dose aspirin does not provide clear cardiovascular benefit in primary prevention for patients with type 2 diabetes
2. The risk of gastrointestinal bleeding is significantly increased with aspirin use
3. Current guidelines reflect this evidence, suggesting aspirin may be considered for primary prevention only after careful discussion of risks and benefits 4

Key Takeaways

• PREVENT/JPAD provides important evidence against routine use of aspirin for primary prevention in diabetes
• The risk-benefit balance does not favor aspirin use in this population
• These findings have influenced current clinical guidelines that now take a more cautious approach to aspirin for primary prevention in diabetes

The PREVENT trial represents an important contribution to our understanding of aspirin's limited role in primary prevention for patients with diabetes, highlighting the need to carefully weigh cardiovascular benefits against bleeding risks.