Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study.
BACKGROUND
Proton-pump inhibitors (PPIs) and clopidogrel are frequently coprescribed, although the benefits and harms of their concurrent use are unclear.


OBJECTIVE
To examine the association between concurrent use of PPIs and clopidogrel and the risks for hospitalizations for gastroduodenal bleeding and serious cardiovascular disease.


METHODS
Retrospective cohort study using automated data to identify patients who received clopidogrel between 1999 through 2005 after hospitalization for coronary heart disease.


METHODS
Tennessee Medicaid program.


METHODS
20,596 patients (including 7593 concurrent users of clopidogrel and PPIs) hospitalized for myocardial infarction, coronary artery revascularization, or unstable angina pectoris.


METHODS
Baseline and follow-up drug use was assessed from automated records of dispensed prescriptions. Primary outcomes were hospitalizations for gastroduodenal bleeding and serious cardiovascular disease (fatal or nonfatal myocardial infarction or sudden cardiac death, stroke, or other cardiovascular death).


RESULTS
Pantoprazole and omeprazole accounted for 62% and 9% of concurrent PPI use, respectively. Adjusted incidence of hospitalization for gastroduodenal bleeding in concurrent PPI users was 50% lower than that in nonusers (hazard ratio, 0.50 [95% CI, 0.39 to 0.65]). For patients at highest risk for bleeding, PPI use was associated with an absolute reduction of 28.5 (CI, 11.7 to 36.9) hospitalizations for gastroduodenal bleeding per 1000 person-years. The hazard ratio associated with concurrent PPI use for risk for serious cardiovascular disease was 0.99 (CI, 0.82 to 1.19) for the entire cohort and 1.01 (CI, 0.76 to 1.34) for the subgroup of patients who had percutaneous coronary interventions with stenting during the qualifying hospitalization.


CONCLUSIONS
Unmeasured confounding and misclassification of exposure (no information on adherence or over-the-counter use of drugs) and end points (not confirmed by medical record review) were possible. Because many patients entered the cohort from hospitals with relatively few cohort members, the analysis relied on the assumption that after adjustment for observed covariates, PPI users from one such hospital could be compared with nonusers from a different hospital.


CONCLUSIONS
In patients with serious coronary heart disease treated with clopidogrel, concurrent PPI use was associated with reduced incidence of hospitalizations for gastroduodenal bleeding. The corresponding point estimate for serious cardiovascular disease was not increased; however, the 95% CI included a clinically important increased risk.


BACKGROUND
Agency for Healthcare Research and Quality and National Heart, Lung, and Blood Institute.
Ray
Wayne A
WA
Vanderbilt University School of Medicine and Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA. Wayne.Ray@vanderbilt.edu
Murray
Katherine T
KT
Griffin
Marie R
MR
Chung
Cecilia P
CP
Smalley
Walter E
WE
Hall
Kathi
K
Daugherty
James R
JR
Kaltenbach
Lisa A
LA
Stein
C Michael
CM
D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D000077144:Clopidogrel; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000517:prevention & control*; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D054328:Proton Pump Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine