Clopidogrel and interaction with proton pump inhibitors: comparison between cohort and within person study designs.
OBJECTIVE
To measure the association between use of proton pump inhibitors and a range of harmful outcomes in patients using clopidogrel and aspirin.


METHODS
Observational cohort study and self controlled case series.


METHODS
United Kingdom General Practice Research Database with linked data from the Myocardial Ischaemia National Audit Project (MINAP) and the Office for National Statistics (the cardiovascular disease research using linked bespoke studies and electronic records (CALIBER) collaboration)


METHODS
24,471 patients receiving clopidogrel and aspirin.


METHODS
The primary outcome was death or incident myocardial infarction. Secondary outcomes were death, incident myocardial infarction, vascular death, and non-vascular death. Comparisons were made between proton pump inhibitor use and non-use.


RESULTS
Of the 24,471 patients prescribed clopidogrel and aspirin, 12,439 (50%) were also prescribed a proton pump inhibitor at some time during the study. Death or incident myocardial infarction occurred in 1419 (11%) patients while they were receiving a proton pump inhibitor compared with 1341 (8%) who were not receiving a proton pump inhibitor. In multivariate analysis, the hazard ratio for the association between proton pump inhibitor use and death or incident myocardial infarction was 1.37 (95% confidence interval 1.27 to 1.48). Comparable results were seen for secondary outcomes and with other 2C19 inhibitors and with non-2C19 inhibitors. With the self controlled case series design to remove the effect of differences between people, there was no association between proton pump inhibitor use and myocardial infarction, with a rate ratio of 0.75 (0.55 to 1.01). Similarly, with the self controlled case series there was no association with myocardial infarction for other 2C19 inhibitors/non-inhibitors.


CONCLUSIONS
The lack of a specific association and the discrepancy between findings of the analyses between and within people suggests that the interaction between proton pump inhibitors and clopidogrel is clinically unimportant.
Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK. ian.douglas@lshtm.ac.uk
Ian J
IJ
Douglas
Stephen J W
SJ
Evans
Aroon D
AD
Hingorani
Anthony M
AM
Grosso
Adam
A
Timmis
Harry
H
Hemingway
Liam
L
Smeeth
D001241:Aspirin / Q000494:pharmacology*; D000077144:Clopidogrel; D015331:Cohort Studies; D003625:Data Collection; D004347:Drug Interactions; D006801:Humans; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000453:epidemiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D016016:Proportional Hazards Models; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D012107:Research Design; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014652:Vascular Diseases / Q000401:mortality
D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin