We recommend selective use of PPIs in patients receiving dual antiplatelet therapy (DAPT) at high risk of upper gastrointestinal (UGI) bleeding (Strong, Moderate).

Values and Preferences

• This recommendation recognizes the risk and consequences of gastrointestinal bleeding and the benefit demonstrated to prevent these events.
• This recommendation recognizes that CYP2C19 inhibition reduces the action of clopidogrel on platelet inhibition. Although the physiological effect has not been clearly demonstrated to have a clinical effect on thrombotic events, it has also not been eliminated.
• Because PPIs with minimal effect on CYP2C19 are widely available, use of such agents is advisable

Practical tips

• PPIs should not be used routinely in all patients taking DAPT but should be considered in patients at higher risk of gastrointestinal bleeding

Use of PPI in patients taking clopidogrel

• Clopidogrel requires metabolic conversion to its active form through the action of CYP2C19
• Some PPIs, notably omeprazole and esomeprazole, are powerful inhibitors of CYP2C19 and reduce the antiplatelet efficacy of clopidogrel
• Results from 2 meta-analyses and a large randomized clinical trial show that PPIs significantly reduce the risk of upper gastrointestinal bleeding in patients on DAPT
• Randomized and population based studies have conflicting results on the significance of this drug interaction on vascular events. However all are limited by methodology and other biases.
• Pantoprazole has minimal effect on CYP2C19 and is a preferred agent when a PPI is used in a patient on clopidogrel