CaPP3 compared daily aspirin at 100 mg and 300 mg vs. 600 mg (the CAPP2 proven dose) for prevention of Lynch syndrome cancers in 1,866 adults with Lynch syndrome across 5 countries, over a median follow-up of 66.4 months (blinded for 2 years, then open-label for 3 years).
Formal non-inferiority vs. 600 mg was not established for either lower dose. However, 100 mg showed nearly identical cancer risk to 600 mg (ITT HR 0.97 [95% CI 0.67–1.42]; IRR 0.94 [95% CI 0.65–1.38]) with fewer adverse events: serious bleeding occurred in 0 patients on 100 mg vs. 11 (1.5%) on 600 mg (p=0.004).
- Non-inferiority was not formally met for 100 mg in the per-protocol analysis for time to first cancer (HR upper CI 1.63 exceeds the 1.5 boundary). - High dropout rate: 39% stopped aspirin within the 2-year blinded phase, limiting per-protocol power. - Compliance was self-reported, introducing potential misclassification bias.
For Lynch syndrome carriers, 100 mg daily aspirin appears to offer similar cancer protection to 600 mg with a markedly better safety profile — no serious bleeding events vs. 1.5% on 600 mg. Clinicians may consider 100 mg as the preferred dose pending longer follow-up data.
