Interv Akut Kardiol. 2013;12(1):34-41

Routine combination of dual antiplatelet therapy with proton pump inhibitors -

Jan Bultas, Debora Karetová

Farmakologický ústav 3. LF UK, Praha

II. interní kardiologicko-angiologická klinika 1. LF UK, Praha

are we not throwing the baby out with the bath water?

Antithrombotic therapy involves an increased risk of bleeding, with gastrointestinal bleeding being particularly feared. Thus, antiplatelet therapy

is often administered concurrently with proton pump inhibitors (PPIs) that reduce the risk of bleeding. Papers dealing with platelet functions as

well as meta-analyses of clinical studies suggest a lower effect of antiplatelet therapy when clopidogrel, acetylsalicylic acid (ASA), or dual therapy

are comedicated with PPIs. In terms of clopidogrel therapy, there is a relative consensus among papers testing platelet aggregability in treatments

using in vitro methods that concurrent administration of PPIs reduces clopidogrel bioactivation and the proportion of constantly active platelets

increases during treatment. The clinical significance of these papers remains unresolved. Meta-analyses of mostly observational or post-hoc

evaluation studies reveal a significant increase in severe atherothrombotic events with concurrent administration of dual antiplatelet therapy

and PPIs. However, the only prospective controlled study failed to confirm this finding. Unfortunately, due to a number of restrictions of the

study (small statistical power, a special dosage form for the administration of clopidogrel with omeprazole, or an enterosolvent form of ASA), the

conclusion on insignificance of the interaction cannot be generally accepted. From a legal perspective, the warning of regulatory bodies against

the combination of clopidogrel and PPIs is still valid. Negative interaction of PPIs with acetylsalicylic acid is far less taken into consideration. Both

a markedly reduced ASA availability with an increase in gastric pH due to PPIs and ASA deacetylation by intestinal esterases significantly limit

the supply of effective acetylsalicylic acid in the circulation, particularly in the portal one. The significance of reduced antiplatelet effect of ASA

following the administration of PPIs is also indicated by the results of retrospective analyses of secondary preventive studies in patients treated

not with clopidogrel, but with ASA only. An increased rate of severe vascular events by more than 40% in patients treated with ASA will have to

be confirmed in prospective studies. The unclear situation concerning the significance of the drug interaction between PPIs and dual antiplatelet

therapy should lead to restraint in a widespread, routine use of this comedication in patients after acute coronary events or coronary interventions.

Keywords: proton pump inhibitors, antiplatelet therapy, clopidogrel, acetylsalicylic acid, drug interactions

Published: February 21, 2013  Show citation