Background/Purpose: There are relatively clear guidelines for the use of low dose aspirin in the general population for primary cardiovascular (CV) prevention, but the risk-benefit calculation may differ in RA.  While RA confers an increased CV risk compared with age and gender matched controls, such patients more likely use NSAIDs and corticosteroids.  Since these therapies associate with bleeding, they might counterbalance potential benefits of low dose aspirin.  We re-analyzed data from the PRECISION trial, in which all patients received an NSAID, to determine the risk-benefit ratio of low dose aspirin for primary CV prevention in RA.

Methods: We conducted a cohort study using data from the PRECISION RCT, including RA patients without a known history of CVD.  From this group, we compared the potential risks and benefits for those using low dose aspirin to those not.  Patients were censored at the first outcome or loss to follow-up.  The primary outcome was major NSAID toxicity, including major adverse CV event (MACE: CV death, non-fatal myocardial infarction, or non-fatal stroke, re-vascularization, hospitalization for unstable angina or transient ischemic attack), clinically significant gastrointestinal events, renal events, and all-cause mortality.  We estimated incidence rates and hazard ratios (HR) using Cox regression.  Covariates considered for entry into the model included CV risk factors, prior ulcer disease, use of steroids, use of statins, use of DMARDs, HAQ score, serum creatinine, and body mass index (BMI).

Results:   We found 1852 subjects with RA in PRECISION without known CVD; 540 reported using low dose aspirin for CV prevention and 1312 did not.  They had an average age of 60 years, 77% were female and 52% used tobacco.  The mean BMI was 31kg/m² and CV risk factors were common: 34% had diabetes, 76% had hypertension, and dyslipidemia in 56%.  The randomized NSAID treatment assignments were well balanced across the aspirin users and non-users.  Any major NSAID toxicity was observed in 79 (6.0%) of non-aspirin users and 37 (6.9%) of aspirin users (p = 0.50) (see Table).   Aspirin users experienced all components of the primary outcome at a similar rate to non-users (see Table).  In age and gender adjusted Cox regression models, low dose aspirin did not associate with a reduction in major NSAID toxicity (HR 0.95, 95% CI 0.64 – 1.40) or with MACE (HR 1.23, 95% CI 0.72 – 2.10)(see Table). Fully adjusted models yielded very similar results for the primary outcome (HR 1.08, 95% 0.69 – 1.69).

Conclusion: RA patients using low dose aspirin had similar risk of major NSAID toxicity and MACE as patients not. Even among this cohort of RA patients with known CV risk factors, the use of low dose aspirin for primary CV prevention appears not to confer clear benefits.  A larger cohort will be needed to confirm, but low dose aspirin may not promote primary prevention of CV events in RA despite their increased risk.