According to GRADE and EBM methodology, here is what ideal scientific evidence would look like to definitively prove or disprove this specific claim, ordered from strongest to weakest evidence.
Randomized Controlled Trial
A multicenter, double-blind, placebo-controlled RCT in 10,000 UK adults aged 40–70 without prior cardiovascular disease, randomly assigning participants to daily naproxen (500 mg) or placebo for 5 years, with all-cause mortality as the primary endpoint, stratified by sex and adjusted for smoking, cancer, and diabetes status. A prospective cohort study tracking 50,000 UK adults aged 40–70 over 10 years, identifying those prescribed naproxen via electronic health records, matching them 1:1 with non-users on age, sex, smoking, cancer, and diabetes, and comparing all-cause mortality rates with Cox regression and sex-stratified interaction terms. Nested Case-Control Study
A nested case-control study within a UK biobank cohort of 100,000 individuals aged 40–70, identifying 2,000 all-cause mortality cases and matching each with 4 controls by age, sex, smoking, cancer, and diabetes, then assessing prior naproxen prescription history via pharmacy records and calculating odds ratios with interaction by sex. A cross-sectional analysis of UK biobank data at a single time point, comparing mortality rates among those with and without recent naproxen prescriptions, adjusting for age, sex, smoking, cancer, and diabetes — though unable to establish temporal sequence. An ecological study comparing regional mortality rates in the UK with regional naproxen prescription volumes, adjusting for regional averages of smoking, diabetes, and cancer prevalence — but unable to link individual exposure to outcome.