[Dilemma between gastroprotection and cardiovascular prevention].
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.
Klinik für Gastroenterologie, Hepatologie und Infektiologie, Otto-von-Guericke Universität, Magdeburg.
M
M
Venerito
A
A
Kandulski
P
P
Malfertheiner
D000483:Alleles; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001241:Aspirin / Q000009:adverse effects* / Q000627:therapeutic use; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000235:genetics / Q000401:mortality / Q000517:prevention & control* / Q000628:therapy; D023903:Coronary Restenosis / Q000517:prevention & control; D065731:Cytochrome P-450 CYP2C19; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D006801:Humans; D008134:Long-Term Care; D009154:Mutation; D009853:Omeprazole / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010438:Peptic Ulcer Hemorrhage / Q000139:chemically induced* / Q000235:genetics / Q000401:mortality / Q000517:prevention & control*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012307:Risk Factors; D016019:Survival Analysis; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole; D013988:Ticlopidine; D001241:Aspirin