What is the clinical evidence from this study?

Study design: Cohort. Population: Patients receiving oral anticoagulant therapy (n=6354). Intervention: Nonsteroidal anti-inflammatory drugs (NSAIDs) vs. No NSAID use (oral anticoagulant therapy alone). Primary outcome: Gastrointestinal (GI) bleeding (HR 3.01, 95% CI 1.63 to 5.55).

April 29, 2022British Journal of Clinical Pharmacology132 citationsOpen Access

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

LPLeonie S. Penner SGSean P. Gavan DADarren M. Ashcroft

Key Result

Coprescribing NSAIDs with oral anticoagulants increased the risk of gastrointestinal bleeding (HR 3.01) and stroke (HR 2.71) compared to oral anticoagulant therapy alone.

Study Design

Type

Cohort (n=6,354)

Multicenter

Yes

Structured PICO

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

Population

6,354 adults receiving oral anticoagulant (OAC) therapy (vitamin-K antagonists or DOACs), mean age 70, 41% female, UK-based. Key inclusion: aged ≥18 years, at least 1 OAC prescription, registered with a CPRD-participating practice for at least 12 months prior to cohort entry. Matched cohort consisted of 3,177 patients with OAC therapy alone and 3,177 with at least 1 concomitant NSAID prescription.

Intervention

Nonsteroidal anti-inflammatory drugs (NSAIDs) coprescribed with oral anticoagulants (evaluated as a time-dependent exposure)

Comparator

Oral anticoagulant therapy alone (no NSAID prescription during follow-up)

Outcome

Gastrointestinal (GI) bleeding and strokesafety

Coprescribing NSAIDs with oral anticoagulants significantly increases the risk of major bleeding and stroke, highlighting the need to avoid this hazardous combination in primary care.

Main Result

Effect estimate: HR 3.01 (95% CI 1.63 to 5.55)

Absolute Event Rate: 20.49% vs 6.87%

Limitations

Risk of unmeasured confounding due to variables not recorded in the dataset, such as poor INR control
Potential for residual confounding due to measurement error, such as misclassified diagnoses or ICD-codes
Potential for unmeasured NSAID exposure due to over-the-counter purchases not recorded in the database
The indication for NSAID use was not recorded

Abstract

AIMS: 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 cause-specific 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.

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