Omeprazole-clopidogrel interaction and neurovascular complications after flow-diverter device placement

Omeprazole is a common proton pump inhibitor that interferes with the hepatic activation of clopidogrel and potentially reduces its platelet-inhibitory effect. Omeprazole has been shown to increase P2Y₁₂ levels and adverse cardiovascular outcomes in patients treated with drug-eluting stents. However, omeprazole use among patients treated with flow-diverting stents for intracranial aneurysms has not been evaluated.

All patients with placement of a flow-diverting device for treatment of an intracranial aneurysm at a tertiary institution from January 1, 2014, to December 31, 2018, were retrospectively analyzed. Inclusion criteria included documented clopidogrel administration, available P2Y₁₂ levels, and thorough documentation of administration of other medications, including omeprazole.

A total of 138 patients met the inclusion criteria. Sixteen patients (12%) were receiving omeprazole and clopidogrel at treatment. P2Y₁₂ reactivity was significantly greater in the omeprazole cohort (mean P2Y₁₂ level, 250 P2Y₁₂ reaction units (PRU)) than in the control cohort (mean P2Y₁₂ level, 112PRU) (P<0.001). Furthermore, a greater proportion of patients had a P2Y₁₂ level >180 PRU in the omeprazole cohort (14 of 16 [88%] vs 24 of 122 [20%]; P<0.001; OR [95% CI], 29 [6-134]).

Omeprazole was associated with a significant increase in the mean P2Y₁₂ reactivity level among patients with intracranial aneurysms treated with flow-diverting devices who received clopidogrel. However, receipt of omeprazole was not associated with an increased risk of ischemic events or stent stenosis. For neuroendovascular patients who are treated with a flow diverter while receiving clopidogrel, alternative gastrointestinal medication regimens should be considered.