One-year clinical outcome in patients with acute coronary syndrome treated with concomitant use of clopidogrel and proton pump inhibitors:  results from a regional cohort study.
OBJECTIVE
We sought to compare the 1-year risk of re-hospitalization for acute coronary syndrome (ACS) between patients taking clopidogrel with proton pump inhibitors (PPIs) vs. clopidogrel without PPIs.


METHODS
We conducted a retrospective cohort study among 3896 patients with ACS, at low risk for gastrointestinal bleeding, discharged from all hospitals of the Emilia-Romagna region of Italy during the period January-August 2008. Patients' consumption of clopidogrel and PPIs at hospital discharge and follow-up was based on pharmacy refill data. Of these 3896 patients, 90% (n = 3519) were prescribed PPIs at hospital discharge and/or at some time during follow-up.


RESULTS
At 1-year follow-up, hospitalization for ACS occurred in 15% of patients taking clopidogrel with PPIs vs. 3.4% of those taking clopidogrel without PPIs (P < 0.001). No difference in terms of all-cause mortality could be detected between the two groups. At multivariate regression analysis with PPI use as a time-varying covariate, periods of use of clopidogrel with PPIs were associated, at 1-year follow-up, with a significantly higher risk of hospitalization for ACS (hazard ratio 1.29, P = 0.025). Notably, this event occurred mostly in patients who underwent revascularization during the index hospitalization (n = 3045, hazard ratio 1.52, P = 0.004). No significant effect of PPI prescription could be observed in terms of 1-year all-cause mortality and revascularization.


CONCLUSIONS
This study suggests the hypothesis that a concomitant use of clopidogrel and PPIs in patients with ACS, at low risk for gastrointestinal bleeding, having mostly undergone coronary revascularization, is associated with an approximately 30% higher risk of nonfatal hospitalization for ACS.
Institute of Cardiology, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. paortol@tin.it
Paolo
P
Ortolani
Massimiliano
M
Marino
Antonio
A
Marzocchi
Rossana
R
De Palma
Angelo
A
Branzi
D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D004347:Drug Interactions; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010359:Patient Readmission; 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; D013997:Time Factors; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine