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[Dilemma between gastroprotection and cardiovascular prevention]
M Venerito1, A Kandulski, P Malfertheiner
1Klinik für Gastroenterologie, Hepatologie und Infektiologie, Otto-von-Guericke Universität, Magdeburg.
Insights
Long-term aspirin and clopidogrel use increases gastrointestinal bleeding risk. While proton pump inhibitors (PPIs) can reduce this risk, omeprazole may decrease clopidogrel
Area of Science:
- Pharmacology
- Gastroenterology
- Cardiology
Background:
- Low-dose aspirin and clopidogrel increase upper gastrointestinal (GI) bleeding risk.
- Proton pump inhibitors (PPIs) are used for gastric protection in patients on antiplatelet therapy.
- A potential interaction between PPIs and clopidogrel raises concerns about reduced clopidogrel efficacy.
Purpose of the Study:
- To review literature on PPI use for gastric protection in patients on antiplatelet therapy.
- To focus on the potential interaction between clopidogrel and PPIs.
- To evaluate the impact of PPIs on clopidogrel's efficacy.
Main Methods:
- Selected literature review.
- Analysis of ex vivo platelet function studies.
- Evaluation of in vivo evidence regarding clopidogrel-PPI interaction.
Main Results:
- Ex vivo studies showed reduced clopidogrel efficacy with omeprazole, but not other PPIs.
- No clear in vivo evidence currently exists to confirm PPIs reduce clopidogrel efficacy.
- A split-dosage regimen (PPI in morning, clopidogrel in evening) is suggested if co-prescription is necessary.
Conclusions:
- The interaction between clopidogrel and PPIs requires careful consideration.
- Current evidence does not definitively prove that PPIs compromise clopidogrel efficacy in vivo.
- A split-dosage regimen may mitigate potential risks associated with concomitant clopidogrel and PPI use.
Abstract:
Long-term low-dose aspirin intake leads to a 2 - 4-fold risk of risk for upper gastrointestinal bleeding. The additional intake of clopidogrel further increases the risk of upper GI bleeding (OR 7.4). Because of the potential interaction between proton pump inhibitors (PPI) and clopidogrel that compromises the efficacy of clopidogrel on platelet aggregation, there has been a warning in the product information by health authorities in the US and in Europe who discourage the concomitant use of PPI and clopidogrel. In the present study we performed a selected review of the published literature on the indications for gastric protection with PPI in patients on mono- or dual antiplatelet therapy focussing on the possible interaction between clopidogrel and PPI. In ex vivo analyses of platelet function, a reduced efficacy of clopidogrel was observed in patients on comedication with omeprazole. This was not the case with the comedication of other PPIs. To date, clear evidence is missing to state that comedication with PPI reduces the efficacy of clopidogrel IN VIVO. If both Clopidogrel and PPI need to be prescribed, a split dosage regimen of PPI in the morning and clopidogrel in the evening can be recommended. The short half-life of both medications explains the rationale of this recommendation.
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