Single antiplatelet therapy for patients with previous gastrointestinal bleeds.
OBJECTIVE
To determine whether aspirin plus a proton pump inhibitor (PPI) is preferable, from a gastrointestinal bleed (GIB) risk perspective, to clopidogrel in patients who have experienced a GIB while on aspirin and who require single antiplatelet therapy for secondary prevention of cardiovascular disease.


METHODS
A literature search was conducted using EMBASE (1980-January 2008), PubMed (1966-January 2008), Google, and a manual search of the reference lists using the search terms gastrointestinal bleed, gastrointestinal hemorrhage, peptic ulcer hemorrhage, ASA, aspirin, Plavix, clopidogrel, and PPI. The search, limited to human and English studies, yielded 110 returns.


METHODS
Randomized trials that compared aspirin with clopidogrel, involved patients who had previously experienced a GIB, and provided detailed information on the type and dose of drugs used were included. Studies were required to provide information on the recurrence of GIB.


RESULTS
Two randomized trials were reviewed to assess the safety of secondary prevention of cardiovascular disease with respect to previous GIB. These noninferiority trials compared aspirin plus a PPI with clopidogrel over 12 months following confirmed healing of an aspirin-induced ulcer. In both trials, the majority of the GIB recurrences were in the clopidogrel group (8.6% vs 0.7%; difference 7.9%; 95% CI 3.4 to 12.4; p = 0.001 and 13.6% vs 0%; difference 13.6%; 95% CI 6.3 to 20.9; p = 0.0019) and the difference in recurrence rates exceeded the a priori selected upper boundary.


CONCLUSIONS
Findings reported in the limited literature available support that clopidogrel is not equivalent to the combination of aspirin plus a PPI in the patient population studied. Aspirin plus a PPI would be considered clinically superior and should be used in medically managed patients who require single antiplatelet therapy but have had a prior GIB while on aspirin. Further research regarding dual antiplatelet therapy and a PPI is required.
Gellatly
Rochelle M
RM
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Ackman
Margaret L
ML
D000368:Aged; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000517:prevention & control; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin