本帖最後由 goodcat1111 於 2009-4-5 08:50 編輯
作者：Laurie Barclay, MD
出處：WebMD醫學新聞
March 2, 2009 — 根據2月17日內科醫學檔案期刊發表的一篇隨機控制試驗結果，成功內視鏡治療後，使用靜脈注射高劑量esomeprazole，可以降低消化性潰瘍病患的出血風險。
中國香港中文大學的Joseph J.Y. Sung醫師與消化性潰瘍出血研究小組的同僚寫道，因為在不同種族有互相矛盾的結果，使用質子幫浦抑制劑(PPIs)治療消化性潰瘍仍有爭議。以高劑量靜脈輸注質子幫浦抑制劑達到完全而持續的抑制胃酸，被視為可以藉由穩定較高的胃酸值而改善結果。
研究目標是確認靜脈注射esomeprazole對於預防復發消化性潰瘍出血是否比安慰劑有效，研究對象是多種族病患樣本。
在2005年10月至2007年12月間，從16個國家的91家醫院急診室募集18歲以上的消化性潰瘍出血病患。參與者有單一胃潰瘍或十二指腸潰瘍出血高風險病灶，在隨機分組之前，全都接受成功的內視鏡止血。參與者、醫師與研究者都不清楚分組指派情況。
透過電腦隨機分組，參與者被指派接受esomeprazole 80-mg 靜脈注射，之後以每小時8-mg輸注72小時，或者是安慰劑。輸注之後，這兩組病患都給予口服的esomeprazole、每天40 mg、共27天。研究的主要結果是72小時內臨床明顯復發出血的比率，其他結果是7-30天內的復發出血、死亡、手術、內視鏡再度治療、輸血、住院與安全性等。
隨機指派的767名參與者中，有764名資料進行治療意向分析，其中375人在esomeprazole組，389人在安慰劑組。
接受靜脈輸注esomeprazole的375名病患，有22人在72小時內復發出血，接受安慰劑的389人有40人發生(5.9% 相較於10.3%;95%差異信心區間[CI]為0.6% - 8.3%; P = .026)。在第7和30天，復發出血的差異依舊明顯(P = .010)。
Esomeprazole組明顯較少需要以內視鏡再度治療(6.4%相較於11.6%; 95%差異信心區間為1.1% - 9.2%; P = .012)。相較於安慰劑，減少手術比率也較低，但不顯著(2.7%相較於5.4%) ，各種原因死亡率也是(0.8%相較於2.1%)。
在兩組中，嚴重副作用(AEs)比率約有10%，不嚴重副作用的病患約有40%。
研究作者寫道，高風險消化性潰瘍出血病患於成功內視鏡治療之後以靜脈輸注高劑量esomeprazole，可以減少72小時的復發出血，且臨床效果持續達30天。因為esomeprazole組復發出血比安慰劑組少，這也減少了內視鏡再度治療、輸血、住院天數。
研究限制包括內視鏡治療不完全標準；有些病患接受epinephrine 注射、熱凝結或者只用止血夾，而其他可能接受多種治療；esomeprazole組較少Forrest分類 Ia潰瘍；無法偵測低死亡率的差異。
研究作者結論表示，我們相信，這是第一個提供高品質證據，支持於主要為高加索人口之族群，使用靜脈輸注高劑量esomeprazole作為高風險內視鏡病灶與消化性潰瘍出血病患之輔助治療的國際試驗。就我們的看法，此資料指出的PPI用於預防付發消化性潰瘍出血的效果，並無種族特定性，應可以廣泛運用。
日本Dokkyo醫學大學胃腸科主任Hideyuki Hiraishi博士(教授)、Akihiro Tajima博士(助理教授)、Tadahito Shimada博士(副教授)等人為Medscape提供對此研究的獨立評論。
他們向Medscape表示，結果認為最初3天內的治療對消化性潰瘍很重要，但是各種內視鏡止血方法對於esomeprazole和安慰劑這兩組在潰瘍癒合上也有不同效果。
他們表示，靜脈注射esomeprazole以預防復發消化性潰瘍出血可以降低不必要的內視鏡檢查。Esomeprazole組比較常發生輸注部位反應。連續輸注時可以考慮降低劑量。
至於後續研究，他們認為，以固定劑量的esomeprazole取代安慰劑用於控制治療，以顯示出高劑量esomeprazole在降低復發出血的實際效果。
他們表示，esomeprazole對於消化性潰瘍在不同種族可能有不同效果。反覆消化性潰瘍者在潰瘍疤痕週邊的肌瘤比較明顯，內視鏡止血效果也有不同。至少從這兩個觀點看來，量身訂做的治療，例如以不同的esomeprazole劑量用於消化性潰瘍，則仍需進一步研究。
製造esomeprazole的阿斯特捷利康藥廠的研發部門資助本研究，雇用其中 3名作者，其他4名作者宣稱有各種財務關係，其中1人接受Olympus的獎助金。Tajima、Shimada與 Hiraishi等醫師未宣告任何相關財務關係。
Ann Intern Med. 線上發表於2009年2月17日。
High-Dose Intravenous Esomeprazole May Reduce Recurrent Peptic Ulcer Bleeding
By Laurie Barclay, MD
Medscape Medical News
March 2, 2009 — High-dose intravenous esomeprazole given after successful endoscopic therapy may reduce recurrent bleeding in high-risk patients with peptic ulcer, according to the results of a randomized controlled trial reported in the February 17 Online First issue of the Annals of Internal Medicine.
"Use of proton-pump inhibitors in the management of peptic ulcer bleeding is controversial because of discrepant results reported in different ethnic groups," write Joseph J.Y. Sung, MD, from the Chinese University of Hong Kong in China, and colleagues from the Peptic Ulcer Bleed Study Group. "Profound and sustained acid suppression, as achieved with high-dose intravenous proton-pump inhibitors (PPIs), is thought to improve outcomes by clot stabilization at higher gastric pH."
The goal of this study was to determine whether intravenous esomeprazole was more effective than placebo at preventing recurrent peptic ulcer bleeding in a multiethnic patient sample.
Between October 2005 and December 2007, patients 18 years or older with peptic ulcer bleeding were enrolled from 91 hospital emergency departments in 16 countries. Participants had bleeding from a single gastric or duodenal ulcer with high-risk stigmata, and all had successful endoscopic hemostasis before randomization. Participants, clinicians, and investigators were blinded as to group assignment.
Through computer-generated randomization, participants were assigned to receive either esomeprazole, 80-mg intravenous bolus followed by 8-mg/hour infusion for 72 hours, or matching placebo. After infusion, patients in both groups were given oral esomeprazole, 40 mg/day, for 27?days. The main outcome of the study was rate of clinically significant recurrent bleeding within 72 hours, and other outcomes were recurrent bleeding within 7 and 30 days, death, surgery, endoscopic re-treatment, blood transfusions, hospitalization, and safety.
Of 767 participants who were randomly assigned, data were available for an intent-to-treat analysis in 764, of whom 375 were in the esomeprazole group and 389 in the placebo group.
Recurrent bleeding within 72 hours occurred in 22 of 375 patients receiving intravenous esomeprazole vs 40 of 389 receiving placebo (5.9% vs 10.3%; 95% confidence interval [CI] of difference, 0.6% - 8.3%; P = .026). At 7 days and 30 days, the difference in bleeding recurrence was still significant (P = .010).
Endoscopic re-treatment was significantly less in the esomeprazole group (6.4% vs 11.6%; 95% CI of difference, 1.1% - 9.2%; P = .012). Compared with placebo, there was also a nonsignificant trend for lower rates of surgery (2.7% vs 5.4%) and all-cause mortality (0.8% vs 2.1%).
In both groups, serious adverse events (AEs) were reported in approximately 10% and nonserious AEs in approximately 40% of patients.
"High-dose intravenous esomeprazole given after successful endoscopic therapy to patients with high-risk peptic ulcer bleeding reduced recurrent bleeding at 72 hours and had sustained clinical benefits for up to 30 days," the study authors write. "This was accompanied by a reduction in endoscopic re-treatment, blood transfusions, and hospital stays because of recurrent bleeding in the esomeprazole group compared with the placebo group."
Limitations of this study include endoscopic therapy not completely standardized; some patients receiving epinephrine injection, thermal coagulation, or hemoclips alone, whereas others receiving combination therapy; slight baseline imbalance with fewer Forrest class Ia ulcers in the esomeprazole group; and insufficient power to detect differences in low mortality rates.
"We believe that this is the first international trial to provide high-quality evidence supporting the use of high-dose intravenous esomeprazole as adjuvant therapy to endoscopic therapy for patients with high-risk endoscopic lesions and peptic ulcer bleeding in a predominantly Caucasian population," the study authors conclude. "In our view, the data indicate that the efficacy of PPIs [proton pump inhibitors] in preventing recurrent peptic ulcer bleeding is not race-specific and should be universally applied."
Medscape obtained independent commentary on this study from Akihiro Tajima, MD, PhD (assistant professor), Tadahito Shimada, MD, PhD (associate professor), and Hideyuki Hiraishi, MD,, PhD (chief and professor), all from the Department of Gastroenterology, Dokkyo Medical University in Mibu, Tochigi, Japan.
They told Medscape that the results suggest that early treatment within the first 3 days is important for ulcer cure but that various methods for endoscopic hemostasis might have some different effects on ulcer healing in the esomeprazole and placebo groups.
"Intravenous esomeprazole for prevention of recurrent peptic ulcer bleeding would reduce unnecessary repeated endoscopy," they said. "Infusion-site reactions were more common in the esomeprazole group. Dose reduction might be considered in the continuous infusion phase."
Regarding future research, they suggest that regular-dose esomeprazole, instead of placebo, should be used as a control therapy to show the actual effect of high-dose esomeprazole on the reduction of recurrent bleeding.
"The effect of esomeprazole upon peptic ulcer may be different among several races," they said. "Fibrosis around ulcer scars might be obvious in repeated peptic ulcers, suggesting some difficulties in endoscopic hemostasis. From at least these two viewpoints, tailor made therapy, such as a different dose of esomeprazole, for peptic ulcers needs to be [tested with] additional research."
AstraZeneca Research and Development, the maker of esomeprazole, funded this study, employs 3 of the study authors, and has disclosed various financial relationships with 4 other study authors, 1 of whom also received honoraria from Olympus. Drs. Tajima, Shimada, and Hiraishi have not disclosed any relevant financial relationships.
Ann Intern Med. Published online February 17, 2009. |
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