What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Patients requiring warfarin therapy. Intervention: Warfarin and NSAID vs. Warfarin alone. Primary outcome: Gastrointestinal bleeding (OR 1.98, 95% CI 1.55-2.53, p=<0.001).

May 26, 2020Open Access

Risk of Bleeding with Exposure to Warfarin and Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review and Meta-Analysis

Q: What are the key findings of this study?

Concomitant use of warfarin and an NSAID significantly increased the risk of gastrointestinal bleeding compared to taking warfarin alone (OR 1.98).

LZLorenzo Villa ZapataUniversity of Georgia PHPhilip D. HanstenUniversity of Washington JPJennifer PanicFroedtert Hospital

Key Result

Concomitant use of warfarin and an NSAID significantly increased the risk of gastrointestinal bleeding compared to taking warfarin alone (OR 1.98).

Study Design

Type

Meta-Analysis

Structured PICO

Does concomitant use of warfarin and NSAIDs increase the risk of bleeding compared to warfarin alone in individuals taking warfarin?

Population

Individuals exposed to warfarin (meta-analysis of 11 studies)

Intervention

Concomitant use of warfarin and nonsteroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors

Comparator

Warfarin alone

Outcome

Gastrointestinal bleeding and general bleedingsafety

Concomitant use of warfarin and NSAIDs or COX-2 inhibitors significantly increases the risk of gastrointestinal and general bleeding compared to warfarin alone.

Main Result

Effect estimate: OR 1.98 (95% CI 1.55-2.53)

p-value: p=<0.001

Limitations

Observational nature of included studies makes assessing causality challenging due to potential confounders.
Inability to evaluate the effects of patient demographics, comorbidities, or indications of use on bleeding risk due to lack of reporting.
Moderate to high heterogeneity observed when all NSAIDs were evaluated.
Definitions used for bleeding events varied across the included studies.

Abstract

BACKGROUND: Warfarin use can trigger the occurrence of bleeding independently or as a result of a drug-drug interaction when used in combination with nonsteroidal anti-inflammatory drugs (NSAIDs). OBJECTIVES: This article examines the risk of bleeding in individuals exposed to concomitant warfarin and NSAID compared with those taking warfarin alone (Prospero Registry ID 145237). METHODS: . Risk of bias was also assessed using the Agency for Healthcare Research and Quality bias assessment tool. RESULTS: A total of 651 studies were identified, of which 11 studies met inclusion criteria for meta-analysis. The odds ratio (OR) for gastrointestinal bleeding when exposed to warfarin and an NSAID was 1.98 (95% confidence interval CI: 1.55-2.53). The risk of gastrointestinal bleeding was also significantly elevated with exposure to a COX-2 inhibitor and warfarin relative to warfarin alone (OR = 1.90, 95% CI: 1.46-2.46). There was an increased risk of general bleeding with the combination of warfarin with NSAIDs (OR = 1.58, 95% CI: 1.18-2.12) or COX-2 inhibitors (OR = 1.54, 95% CI: 0.86-2.78) compared with warfarin alone. CONCLUSION: Risk of bleeding is significantly increased among persons taking warfarin and a NSAID or COX-2 inhibitor together as compared with taking warfarin alone. It is important to caution patients about taking these medications in combination.

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