Increased use of acid-suppressing drugs before the occurrence of ischemic events: a potential source of confounding in recent observational studies.

STUDY OBJECTIVE

To determine if the use of acid-suppressing drugs is increased before the occurrence of ischemic events.

DESIGN

Population-based, nested case-control analysis.

DATA SOURCE

Administrative databases in Saskatchewan, Canada.

PATIENTS

Cases were 1612 patients (aged ≥ 40 yrs) who started a first-ever antihypertensive drug between January 1, 1994, and December 31, 2003, and were hospitalized for a first ischemic heart event of either myocardial infarction (1002 patients) or unstable angina (610 patients); five control patients were matched to each case patient by age, sex, and year of first antihypertensive prescription (8060 controls).

MEASUREMENTS AND MAIN RESULTS

Within the case and control groups, we calculated exposure to acid-suppressing therapy, defined as proton pump inhibitors (PPIs) or histamine(2)-receptor antagonists (H(2)RAs), within 90 days leading up to the event. Exposure to acid-suppressing therapy was higher among cases than controls (15.3% [246/1612] vs 10.4% [837/8060], adjusted odds ratio [AOR] 1.26, 95% confidence interval [CI] 1.06-1.49, p<0.009). Exposure to each acid suppressant was similarly higher among cases than controls: H(2)RA users (11.7% [188/1612] vs 8.4% [678/8060], AOR 1.21, 95% CI 1.00-1.46, p<0.048) and PPI users (4.0% [64/1612] vs 2.2% [179/8060], AOR 1.32, 95% CI 0.95-1.84, p=0.094). Use of other drugs was also significantly increased during this period.

CONCLUSIONS

Use of acid-suppressing drugs increased before the occurrence of ischemic events regardless of the type (PPI or H(2)RA) or whether other drugs, such as clopidogrel, were concurrently administered. In addition, significant increases in overall drug use were observed during this time frame, suggesting that many patients exhibit warning signs before an acute hospitalization. Thus, PPI use before the occurrence of ischemic events may simply be a marker of unmeasured and uncontrolled confounding in observational studies that have implicated a PPI-clopidogrel interaction as a cause of recurrent ischemic events.