Key result
Initiation of proton pump inhibitors among warfarin users did not significantly alter mean INR (2.6 before vs 2.6 after initiation; p=0.67), showing no clinically meaningful drug-drug interaction.
Why the study?
Does initiation of proton pump inhibitors increase INR values in patients treated with warfarin?
Observational (n=305)
Does initiation of proton pump inhibitors increase INR values in patients treated with warfarin?
Absolute Event Rate: 2.6% vs 2.6%
p-value: p=0.67
Initiation of proton pump inhibitors in warfarin users does not lead to a clinically meaningful increase in INR, suggesting routine cautious monitoring may be unnecessary.
May allow PPI co-prescription in warfarin users without routine INR adjustment; leaves open prospective trial confirmation.
BACKGROUND: Proton pump inhibitors (PPIs) have been suggested to increase the effect of warfarin, and clinical guidelines recommend careful monitoring of international normalized ratio (INR) when initiating PPI among warfarin users. However, this drug-drug interaction is sparsely investigated in a clinical setting. The aim was to assess whether initiation of PPI treatment among users of warfarin leads to increased INR values. METHODS: The study was an observational self-controlled study from 1998 to 2012 leveraging data on INR measurements on patients treated with warfarin from primary care and outpatient clinics and their use of prescription drugs. Data were analyzed in 2015. We assessed INR, warfarin dose, and dose/INR ratio before and after initiating PPI treatment using the paired student's t-test. RESULTS: We identified 305 warfarin users initiating treatment with PPIs. The median age was 71 years (interquartile range 63-78 years), and 64% were men. The mean INR in the 70 days prior to PPI initiation was 2.6 (95%CI 2.5-2.8) and 2.6 (95%CI 2.5-2.7) in the period 1-3 weeks after PPI initiation (p = 0.67). Further, neither mean warfarin dose nor the dose/INR ratios were significantly different before and after PPI initiation. Sensitivity analyses revealed no differences among individual PPIs. CONCLUSIONS: We found no evidence of a clinically meaningful drug-drug interaction between PPIs and warfarin in a Northern European patient population of unselected patients from an everyday outpatient and primary care clinical setting. Thus, we do not support the recommendation to "cautiously monitor" users of warfarin initiating PPI treatment.
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Henriksen et al. (2015) conducted an observational in Warfarin users (n=305). Proton pump inhibitors vs. Prior to PPI initiation (self-controlled) was evaluated on Mean INR (p=0.67). Initiation of proton pump inhibitors among warfarin users did not significantly alter mean INR (2.6 before vs 2.6 after initiation; p=0.67), showing no clinically meaningful drug-drug interaction.
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