Does coprescribing nonsteroidal anti‐inflammatory drugs and oral anticoagulants increase the risk of major bleeding, stroke and systemic embolism?

Abstract

To examine the risk of gastrointestinal (GI) bleeding, major bleeding, stroke and systemic embolism associated with prescribing nonsteroidal anti-inflammatory drugs (NSAIDs) to adults receiving oral anticoagulant (OAC) therapy. Methods:We conducted a population-based cohort study in adults receiving OAC therapy using linked primary care (Clinical Practice Research Datalink GOLD) and hospital (Hospital Episodes Statistics) electronic health records. We used causespecific Cox regression models with time-dependent NSAID treatment in a propensity score matched population to estimate the increased risk of GI bleeding, stroke, major bleeding and systemic embolism associated with NSAID use. Results:The matched cohort contained 3177 patients with OAC therapy alone and 3177 with at least 1 concomitant NSAID prescription. Compared with OAC therapy alone, concomitant prescription of NSAIDs with OACs was associated with increased risk of GI bleeding (hazard ratio [HR] 3.01, 95% confidence interval [CI] 1.63 to 5.55), stroke (HR 2.71, 95% CI 1.48 to 4.96) and major bleeding (HR 2.77, 95% CI 1.84 to 4.19). The association with systemic embolism did not reach statistical significance (HR 3.02, 95% CI 0.82 to 11.07). Sensitivity analyses indicated that the results were robust to changes in exclusion criteria and the choice of potential confounding variables. Conclusion:When OACs are coprescribed with NSAIDs, the risk of adverse bleeding events increases and, simultaneously, the protective effect of OACs to prevent strokes reduces. There is a need for interventions that reduce hazardous prescribing of NSAIDs in people receiving OAC therapy.

Bleeding and stroke risk from anticoagulant and NSAID

“…The incidence rate for GI bleeding with OAC alone was 6.9 (95% CI 5.3 to 9.0) per 1000 person-years compared with 20.5 (95% CI 11.9 to 35.3) per 1000 person-years with OAC and NSAID (HR 3.01; 95% CI 1.63 to 5.55) 1. The incidence of stroke with OAC alone was 8.0 (95% CI 6.2 to 10.2) per 1000 person-years compared with 20.5 (95% CI 11.9 to 35.3) per 1000 person-years with OAC and NSAID (HR 2.71; 95% CI 1.48 to 4.96).…”

“…This retrospective cohort study involving people taking OACs compared the risk of bleeding and embolic events in new users of NSAIDs with those not prescribed NSAIDs 1. The authors analysed primary care records from the UK Clinical Practice Research Datalink (CPRD) and secondary care data.…”

“…The authors concluded that concomitant use of an OAC and a NSAID was associated with an increased risk of bleeding events and a reduction in the protective effect of OAC against stroke 1…”

“…This study included people who were taking any OAC irrespective of the indication and assessed the impact of concomitant NSAID use on bleeding and thromboembolic events 1. It is worth noting that aspirin was being taken by 29% of participants and only 34% of participants were prescribed gastroprotection.…”

“…A retrospective cohort study found that use of an oral anticoagulant (OAC) with a non-steroidal anti-inflammatory drug (NSAID) was associated with an increased risk of gastrointestinal (GI) bleeding and stroke 1…”