Page 9 - 53-Peptic ulcer diseases (Loét dạ dày)

CHAPTER 53 Peptic Ulcer Disease 813

TABLE 53.1 Risk Factors for NSAID Ulcers* misoprostol in preventing endoscopic ulcers. The superiority of
omeprazole over ranitidine in preventing NSAID-related ulcer was 53
Risk factor Risk ratio due to a greater reduction in endoscopic DUs. A posthoc analysis
History of complicated ulcer 13.5 revealed that most of the added protection attributable to omepra-
zole over ranitidine occurred among those with Hp infection.
Use of multiple NSAIDs (including aspirin, COX-2 inhibitors) 9 Another endoscopic study compared high-dose misoprostol (200
Use of high doses of NSAIDs 7 μg 4 times daily) with 2 doses of lansoprazole (15 and 30 mg daily)
Use of an anticoagulant 6.4 for the prevention of ulcers in long-term NSAID users without
88
History of an uncomplicated ulcer 6.1 Hp infection and with a history of GU. Misoprostol was more
Age >70 years 5.6 effective than either dose of lansoprazole in preventing GU, but
there was no practical advantage of misoprostol over lansoprazole
Hp infection 3.5 because of the high withdrawal rate in the misoprostol group. In
Use of a glucocorticoid 2.2 a head-to-head endoscopic ulcer prevention study comparing 2
doses of pantoprazole with 20 mg/day of omeprazole in patients
*Not all NSAIDs pose the same risk.
with rheumatoid arthritis receiving NSAIDs, the 6-month prob-
abilities of remaining ulcer free were 91%, 95%, and 93% for
pantoprazole 20 mg, pantoprazole 40 mg, and omeprazole 20 mg,
respectively. 89
in the prevention of NSAID-induced ulcers. Antacids may mask Two identical multicenter randomized clinical trials compared
dyspeptic symptoms, thereby creating a false sense of ulcer esomeprazole (20 or 40 mg) with placebo in the prevention of ulcers
protection and increasing the risk of silent ulcer complications in patients taking NSAIDs or COX-2 inhibitors over a 6 month
with prolonged NSAID therapy. Co-prescription of antacids in period. Patients in both studies were Hp negative, older than age
patients taking NSAIDs who are at risk for ulcer should be dis- 60, and had a history of GU or DU. Overall, the rates of ulcers
couraged. were 17.0%, 5.2%, and 4.6% in the groups receiving placebo,
esomeprazole 20 mg, and esomeprazole 40 mg, respectively. 90
H2RAs Whether PPIs can reduce the risk of NSAID-associated peptic
ulcer bleeding is largely based on observational studies and 1 ran-
Using standard doses of H2RAs is not effective in preventing domized trial in high-risk patients. A large-scale, case-control study
NSAID-induced GUs, 84,85 and, as already mentioned, may be found that PPI therapy was associated with a significant reduction
85
harmful. A systematic review of randomized trials in NSAID in risk of UGI bleeding among chronic NSAID users (relative risk,
91
users concluded that using twice the standard daily dose of H2RA 0.13; 95% CI, 0.09 to 0.19). The randomized trial compared
significantly reduces the risk of endoscopic NSAID-induced long-term (6 months) omeprazole therapy to 1 week of Hp eradi-
DUs and GUs. However, whether high-dose H2RAs prevent cation therapy for the prevention of recurrent ulcer bleeding in
NSAID-induced ulcer complications is unknown. In contrast, Hp-infected patients with a recent history of NSAID-related ulcer
92
H2RAs appear to be more effective for prevention of ulcers asso- bleeding who continued to use naproxen. Recurrent ulcer bleed-
ciated with low-dose aspirin than with NSAIDs. In a 12 month, ing occurred in 18.8% of patients undergoing eradication therapy
multi-center randomized trial of low-dose aspirin users at risk for compared with only 4.4% of patients receiving omeprazole.
recurrent ulcer bleeding, there was no significant difference in
the incidence rates of recurrent bleeding between patients receiv- COX-2 Inhibitors (In Place of NSAIDs)
89
ing a PPI and patients receiving an H2RA.
COX-2 inhibitors offer the hope of minimizing GI toxicity of
Misoprostol NSAIDs while preserving their therapeutic effects. 93-97 In a sys-
tematic review of randomized trials, when compared with nonse-
The efficacy of misoprostol in preventing NSAID-induced ulcers lective NSAIDs the COX-2 inhibitors led to significantly fewer
has been assessed in RCTs. 86,87 A systematic review of these tri- gastroduodenal ulcers (relative risk, 0.26; 95% CI, 0.23 to 0.30)
als indicated that all doses of misoprostol studied (400 to 800 and ulcer complications (relative risk, 0.39; 95% CI, 0.31 to 0.5),
μg/day) reduce the risk of NSAID-induced endoscopic ulcers. as well as fewer withdrawals caused by GI symptoms ; however,
94
85
However, only full-dose misoprostol (800 μg/day) reduces ulcer the sparing effect of COX-2 inhibitors on ulcer development is
86
complications. In a randomized double-blind trial in patients negated by concomitant use of low-dose aspirin. 59
with rheumatoid arthritis who received NSAIDs, misoprostol (200 Current evidence indicates that COX-2 inhibitors are as effec-
μg 4 times daily) lowered the rate of GI complications by 40% tive as a combination of nonselective NSAIDs combined with a
(from 0.95% in the placebo group to 0.57% in the misoprostol PPI in patients at risk for ulcers. In a randomized comparison
group). However, up to 30% of misoprostol-treated patients in of the NSAID diclofenac plus omeprazole versus celecoxib for
this trial experienced GI upset, thereby limiting its clinical use. secondary prevention of ulcer bleeding in patients who either
95
Even though endoscopic studies had suggested that lower doses of were Hp negative or had undergone Hp eradication, a similar
misoprostol, such as 200 μg 2 or 3 times daily, can prevent NSAID- proportion of patients had recurrent bleeding in 6 months (6.4%
induced ulcers with fewer adverse effects than the full dose, such in the diclofenac/omeprazole group and 4.9% of patients in the
86
88
low doses of misoprostol fail to prevent ulcer complications. celecoxib group). Although the 2 treatments were comparable in
terms of the incidence of ulcer bleeding, a subsequent follow-up
PPIs endoscopic study showed that 20% to 25% of patients receiv-
ing either treatment developed recurrent endoscopic ulcers at 6
PPIs significantly reduce the risk of endoscopic duodenal and months. These findings suggest that neither treatment can elimi-
GUs. The efficacy of PPIs has been compared with that of nate the risk of recurrent bleeding in very high-risk patients. In
85
H2RAs and with misoprostol in patients who received NSAIDs. a 13-month, double-blind randomized trial comparing celecoxib
Two 6-month studies compared omeprazole 20 mg once daily with alone with celecoxib/esomeprazole in patients with a history of
either standard-dose ranitidine (150 mg twice daily) and half-dose NSAID-associated ulcer bleeding, 8.9% of the celecoxib-alone
misoprostol (200 μg twice daily). 76,80 Omeprazole was more effec- group had recurrent ulcer bleeding compared with none of the
tive than standard-dose ranitidine and comparable with half-dose combined therapy group (P = 0.0004). 96