CAPP2: two years of aspirin cuts bowel cancer in Lynch syndrome by more than a third over 10 years
In carriers of Lynch syndrome, 600 mg of aspirin a day for about two years reduced colorectal cancer over the following decade (HR 0.65 by intention to treat; 0.56 in those who took it for at least two years).
CAPP2 randomised 861 carriers of a mismatch-repair gene mutation (Lynch syndrome) to aspirin 600 mg daily or placebo for a mean of 25 months, in a factorial design with resistant starch. The pre-specified 10-year follow-up reported here used national registries and questionnaires.
By intention to treat, 40 aspirin-arm and 58 placebo-arm participants developed colorectal cancer (HR 0.65). Among those who completed at least two years of treatment, the hazard ratio was 0.56. The protective effect emerged only after about five years and persisted for at least a decade after stopping. Adverse events did not differ during the treatment period.
The result led NICE and other guidelines to recommend daily aspirin for people with Lynch syndrome; the CAPP3 dose-finding trial (100 vs 300 vs 600 mg) followed.
- Colorectal cancer: 40 of 427 on aspirin vs 58 of 434 on placebo, HR 0.65 (95% CI 0.43-0.97) by intention to treat
- Per-protocol (at least 2 years of treatment): HR 0.56 (95% CI 0.34-0.91)
- Protection was delayed, appearing about 5 years after randomisation, and persisted after aspirin was stopped
- No significant difference in serious adverse events during the intervention period
People with Lynch syndrome should be offered daily aspirin, which roughly halves bowel cancer risk with a delayed and durable effect. Whether a lower dose (as tested in CAPP3) is as effective, and whether the finding extends to the general population, are separate questions.
- Original primary endpoint at the 2008 analysis was null; the effect emerged only with long follow-up, which invites scepticism about post-hoc timing
- 600 mg is a high dose with bleeding risk in older people; CAPP3 addresses dose
- Most participants were under 60 and from specialist registries
- Resistant starch, the other factorial arm, showed a reduction in non-colorectal Lynch cancers, complicating interpretation