Histamine2-receptor antagonists are an alternative to proton pump inhibitor in patients receiving clopidogrel.
OBJECTIVE
Previous observational studies reported that concomitant use of clopidogrel and proton pump inhibitors (PPIs) in patients with prior acute coronary syndrome (ACS) was associated with adverse cardiovascular outcomes. We investigated whether H(2)-receptor antagonist (H(2)RA) is an alternative to PPI in patients with ACS.


METHODS
We conducted a population-based retrospective cohort study of 6552 patients in Taiwan discharged for ACS between 2002 and 2005. Patients were divided into 5 cohorts: clopidogrel plus H(2)RA (n = 252), clopidogrel plus PPI (n = 311), clopidogrel alone (n = 5551), H(2)RA alone (n = 235), and PPI alone (n = 203). The primary outcome was rehospitalization for ACS or all-cause mortality within 3 month of rehospitalization.


RESULTS
The 1-year cumulative incidence of the primary outcome was 26.8% (95% CI: 21.5%-33.0%) in the clopidogrel plus H(2)RA cohort and 33.2% (95% CI: 27.8%-39.4%) in the clopidogrel plus PPI cohort, compared with 11.6% (95% CI: 10.8%-12.5%) in the clopidogrel alone cohort (P < .0001). No significant difference was observed between the PPI alone cohort (11.0%; 95% CI: 7.1%-16.8%), the H(2)RA alone cohort (11.8%; 95% CI: 8.2%-16.8%), and the clopidogrel alone cohort in terms of the primary outcome. The number needed to harm was 7 with concomitant H(2)RA and 5 with concomitant PPI. On multivariate analysis, concomitant H(2)RA and PPI were independent risk factors predicting adverse outcomes (adjusted hazard ratios, 2.48 and 3.20, respectively; P < .0001).


CONCLUSIONS
Concomitant use of clopidogrel and H(2)RA or PPI after hospital discharge for ACS is associated with increased risk of adverse outcomes.
Wu
Chun-Ying
CY
Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan. chun@vghtc.gov.tw
Chan
Francis Ka-Leung
FK
Wu
Ming-Shiang
MS
Kuo
Ken N
KN
Wang
Chang-Bi
CB
Tsao
Chen-Rong
CR
Lin
Jaw-Town
JT
D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000502:physiology; D000077144:Clopidogrel; D015331:Cohort Studies; D065731:Cytochrome P-450 CYP2C19; D004359:Drug Therapy, Combination; D005260:Female; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D006635:Histamine H2 Antagonists; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine