Author + information
- Min Sen Yew,
- Poh Shuan Daniel Yeo,
- Jau Lueng Paul Ong,
- Lijuan Mira Shen,
- Hee Hwa Ho,
- Fahim Haider Jafary,
- Yau Wei Ooi,
- Kwok Kong Jason Loh,
- Ko Beng Julian Tan and
- Chee Guan David Foo
Dual anti-platelet therapy (DAPT) with Aspirin and a Thienopyridine-derivative P2Y12 Inhibitor (commonly Clopidogrel) is mandatory after Percutaneous Coronary Intervention (PCI). H2 receptor antagonists (H2RA) or Proton Pump Inhibitors (PPI) are prescribed to reduce gastrointestinal bleeding risk.
Clopidogrel is a prodrug that requires activation by CYP2C19 and other isoenzymes of the cytochrome P450 system. Carriers of a loss-of-function CYP2C19 allele have lower levels of the active metabolite, resulting in reduced platelet inhibition and a potentially higher rate of adverse cardiovascular events. As PPI are competitive inhibitors of CYP2C19, coadministration with Clopidogrel can further reduce the latter’s antiplatelet activity.
The COGENT randomised trial which enrolled predominantly white Caucasian males did not demonstrate any adverse interaction between Clopidogrel and Omeprazole use. However, this interaction may be significant in Asian patients as up to 55% of Asians carry a loss-of-function CYP2C19 allele as compared to 30% of Caucasians. We hypothesize that Asian patients taking both Clopidogrel and the PPI Omeprazole are at higher risk of adverse cardiovascular events post-PCI.
This retrospective cohort study in a 1300-bed tertiary hospital in Singapore included all patients from 1st January to 31st December 2011 who had PCI and received either Omeprazole or a H2RA, together with 12 months of Aspirin and Clopidogrel. Prescription and outcome data were retrieved from electronic medical records. The primary outcome was the incidence of cardiovascular complications within 12 months of the initial PCI. Cardiovascular complication is defined as cardiovascular death, non-fatal myocardial infarction, need for urgent target vessel revascularisation and ischemic stroke.
We identified 933 patients, of which 614 patients met the criteria for inclusion. The primary outcome occurred in 27 of 296 patients (9.1%) from the Omeprazole group and 13 of 318 patients (4.1%) from the H2RA group (p = 0.014). The difference remained statistically significant after adjustment for baseline differences in cardiovascular risk factors in both groups (p = 0.042).
Using Omeprazole rather than a H2RA was associated with a significantly greater incidence of cardiovascular complications in Asian patients on Clopidogrel after PCI. Larger studies are required to further evaluate this observation.