Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding.
BACKGROUND
Concurrent therapy with a proton-pump inhibitor is a standard treatment for patients receiving aspirin who are at risk for ulcer. Current U.S. guidelines also recommend clopidrogel for patients who have major gastrointestinal intolerance of aspirin. We compared clopidogrel with aspirin plus esomeprazole for the prevention of recurrent bleeding from ulcers in high-risk patients.


METHODS
We studied patients who took aspirin to prevent vascular diseases and who presented with ulcer bleeding. After the ulcers had healed, we randomly assigned patients who were negative for Helicobacter pylori to receive either 75 mg of clopidogrel daily plus esomeprazole placebo twice daily or 80 mg of aspirin daily plus 20 mg of esomeprazole twice daily for 12 months. The end point was recurrent ulcer bleeding.


RESULTS
We enrolled 320 patients (161 patients assigned to receive clopidogrel and 159 to receive aspirin plus esomeprazole). Recurrent ulcer bleeding occurred in 13 patients receiving clopidogrel and 1 receiving aspirin plus esomeprazole. The cumulative incidence of recurrent bleeding during the 12-month period was 8.6 percent (95 percent confidence interval, 4.1 to 13.1 percent) among patients who received clopidogrel and 0.7 percent (95 percent confidence interval, 0 to 2.0 percent) among those who received aspirin plus esomeprazole (difference, 7.9 percentage points; 95 percent confidence interval for the difference, 3.4 to 12.4; P=0.001).


CONCLUSIONS
Among patients with a history of aspirin-induced ulcer bleeding whose ulcers had healed before they received the study treatment, aspirin plus esomeprazole was superior to clopidogrel in the prevention of recurrent ulcer bleeding. Our finding does not support the current recommendation that patients with major gastrointestinal intolerance of aspirin be given clopidogrel.
Chan
Francis K L
FK
Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong, China. fklchan@cuhk.edu.hk
Ching
Jessica Y L
JY
Hung
Lawrence C T
LC
Wong
Vincent W S
VW
Leung
Vincent K S
VK
Kung
Nelson N S
NN
Hui
Aric J
AJ
Wu
Justin C Y
JC
Leung
Wai K
WK
Lee
Vivian W Y
VW
Lee
Kenneth K C
KK
Lee
Yuk T
YT
Lau
James Y W
JY
To
Ka F
KF
Chan
Henry L Y
HL
Chung
S C Sydney
SC
Sung
Joseph J Y
JJ
D000368:Aged; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D000077144:Clopidogrel; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D064098:Esomeprazole / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D010438:Peptic Ulcer Hemorrhage / Q000139:chemically induced / Q000517:prevention & control*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D054328:Proton Pump Inhibitors; D055502:Secondary Prevention; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D000897:Anti-Ulcer Agents; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D064098:Esomeprazole; D013988:Ticlopidine; D001241:Aspirin