The potential interaction between clopidogrel and proton pump inhibitors: a systematic review

Area of Science:

• Pharmacology
• Clinical Medicine
• Drug Interactions

Background:

• Concerns exist regarding potential drug interactions between clopidogrel and proton pump inhibitors (PPIs).
• Regulatory agencies have issued warnings despite conflicting study results.
• Study quality and bias may explain discordant findings on clopidogrel-PPI interactions.

Purpose of the Study:

• To systematically review and critically analyze studies on clopidogrel and PPI interactions.
• To determine if study quality (bias) influences reported interaction results.
• To clarify the clinical significance of the clopidogrel-PPI interaction.

Main Methods:

• Systematic review of studies reporting clinical outcomes.
• Literature search included MEDLINE, EMBASE, conference abstracts, and bibliographies.
• Studies were evaluated for risk of bias using a prespecified quality scale.

Main Results:

• 18 studies were identified; 13 low-quality studies reported positive interactions (10/13).
• Five moderate/high-quality studies found no statistically significant association (0/5).
• An inverse correlation was observed between study quality and reported positive interactions (P=0.007).

Conclusions:

• The association between clopidogrel and PPIs is confined to low-quality studies with higher bias.
• High-quality evidence for a clinically significant clopidogrel/PPI interaction is currently lacking.
• No clinical evidence supports a positive interaction with specific PPIs.