Risk of rehospitalization for patients using clopidogrel with a proton pump inhibitor.
BACKGROUND
Recent pharmacodynamic and retrospective clinical analyses have suggested that proton pump inhibitors (PPIs) may modify the antiplatelet effects of clopidogrel bisulfate.


METHODS
We conducted a retrospective cohort study of persons enrolled in a multistate health insurance plan with commercial and Medicare clients to evaluate adverse clinical outcomes in patients using clopidogrel plus a PPI compared with clopidogrel alone. Patients who were discharged from the hospital after myocardial infarction (MI) or coronary stent placement and treated with clopidogrel plus a PPI (n = 1033) were matched 1:1 (using propensity scoring) with patients with similar cardiovascular risk factors treated with clopidogrel alone. Rehospitalizations for MI or coronary stent placement were evaluated for up to 360 days. A subanalysis was conducted to study the impact of pantoprazole sodium, the most used PPI.


RESULTS
Patients who received clopidogrel plus a PPI had a 93% higher risk of rehospitalization for MI (adjusted hazard ratio, 1.93; 95% confidence interval, 1.05-3.54; P = .03) and a 64% higher risk of rehospitalization for MI or coronary stent placement (1.64; 1.16-2.32; P = .005) than did patients receiving clopidogrel alone. Increased risk of rehospitalization for MI or coronary stent placement was also observed for the subgroup of patients receiving clopidogrel plus pantoprazole (adjusted hazard ratio, 1.91; 95% confidence interval, 1.19-3.06; P = .008).


CONCLUSIONS
Patients who received clopidogrel plus a PPI had a significantly higher risk of rehospitalization for MI or coronary stent placement than did patients receiving clopidogrel alone. Prospective clinical trials and laboratory analyses of biochemical interactions are warranted to further evaluate the potential impact of PPIs on the efficacy of clopidogrel.
Stockl
Karen M
KM
PharmD, Outcomes Research, Department of Clinical Services, Prescription Solutions, 2300 Main St, Mail Stop CA 134-0404, Irvine, CA 92614, USA. karen.stockl@rxsol.com
Le
Lisa
L
Zakharyan
Armen
A
Harada
Ann S M
AS
Solow
Brian K
BK
Addiego
Joseph E
JE
Ramsey
Scott
S
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D000077144:Clopidogrel; D015331:Cohort Studies; D016001:Confidence Intervals; D023903:Coronary Restenosis / Q000453:epidemiology* / Q000209:etiology; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D010359:Patient Readmission / Q000706:statistics & numerical data*; D011336:Probability; D016016:Proportional Hazards Models; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012016:Reference Values; D012189:Retrospective Studies; D018570:Risk Assessment; D012737:Sex Factors; D015996:Survival Rate; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine