Oral PPIs for acute peptic ulcer bleeding: Not quite ready for prime time
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Oral PPI therapy gets nod following bleeding ulcer repair

CHICAGO – Oral proton pump inhibitor therapy on the medical ward following endoscopic treatment of patients with a bleeding ulcer is equally effective as the current guideline-recommended practice of administering a PPI bolus followed by a 72-hour continuous intravenous infusion – and a lot less resource intensive.

That’s the highly practical message from a meta-analysis of randomized trials addressing the issue that Dr. Hamita Sachar presented at the annual Digestive Disease Week.

Dr. Hamita Sachar

Current national and international guidelines recommend an intravenous 80-mg bolus of PPI followed by a 72-hour infusion at 8 mg/hr after successful endoscopic therapy of a high-risk bleeding ulcer. These guidelines need to be revisited in light of the new data, according to Dr. Sachar, a fellow in digestive diseases at Yale University, New Haven, Conn.

"This is practice changing. Intermittent oral therapy is less expensive. Also, it’s quite easy to administer. If you can get away with twice-daily oral dosing, it’s preferred over an IV infusion by patients, it requires less nursing time, and there’s less pharmacy personnel time. As long as patients don’t have nausea and vomiting, I think it’s reasonable for them to get oral therapy because equivalent doses of IV and oral drug have exactly the same pharmacokinetic profiles," she said in an interview.

The meta-analysis, which featured a noninferiority design, included a dozen randomized trials totaling more than 1,600 patients. The primary outcome was the rate of rebleeding within 7 days. It turned out to be virtually identical in the two groups.

Moreover, there was no significant difference between patients who received intermittent oral PPI therapy at standard doses and those who got the guideline-recommended bolus, continuous-infusion regimen in terms of any of the secondary endpoints in the meta-analysis, which included rebleeding within 30 days, rebleeding within 3 days, need for blood transfusion, urgent surgical or endoscopic interventions, and length of hospital stay.

Dr. Sachar and her coinvestigators performed the meta-analysis because their physiologic model suggested that intravenous therapy was safely avoidable. They noted that several randomized trials in the literature concluded that the two treatment strategies might yield comparable outcomes; however, the individual studies were too small to allow any firm conclusions to be drawn.

The study was supported by institutional funds. Dr. Sachar reported having no financial conflicts regarding this study.

bjancin@frontlinemedcom.com

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Sachar and colleagues presented an interesting systematic review and meta-analysis at DDW 2014 (Gastroenterology 2014;146(5 Suppl 1):S-75). This presentation has fueled discussions on whether high-risk patients with peptic ulcer bleeding (those who had successful endoscopic hemostasis for high-risk stigmata) should receive PPIs intermittently (intravenously or even orally) as opposed to the current practice of high-dose continuous intravenous infusion.

Dr. Grigorios I. Leontiadis
In my opinion, it is premature to change practice. For any research, and more so for systematic reviews, truth is in the details - and such details can only be assessed when the full publication is available. Based on the limited information currently available, this systematic review was been well conducted, but the quality of evidence (the trustworthiness of the results) is undermined by the characteristics of the included studies. All included studies were randomized controlled trials, but only one was at low risk for selection bias, and most of them were at high risk for detection bias. Furthermore, the generalizability to Western populations is limited because the majority of the studies were conducted in homogeneous Asian populations. Asian patients with peptic ulcer bleeding are particularly responsive to PPI treatment (Cochrane Database Syst. Rev. 2006;[1]:CD002094). Therefore, Asian studies may be more likely to show noninferiority than Western studies.

In conclusion, until the quality of the evidence can be fully assessed, it would be prudent to adhere to the recommendations from the existing practice guidelines and treat high-risk patients with peptic ulcer bleeding with high-dose intravenous infusion PPI treatment, since this is the only dose that has been proven to reduce not only rebleeding but also mortality.

Dr. Grigorios I. Leontiadis is assistant professor of medicine, division of gastroenterology, McMaster University, Hamilton, Ont. He was a consultant to a PPI manufacturer more than 5 years ago.
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Body

Sachar and colleagues presented an interesting systematic review and meta-analysis at DDW 2014 (Gastroenterology 2014;146(5 Suppl 1):S-75). This presentation has fueled discussions on whether high-risk patients with peptic ulcer bleeding (those who had successful endoscopic hemostasis for high-risk stigmata) should receive PPIs intermittently (intravenously or even orally) as opposed to the current practice of high-dose continuous intravenous infusion.

Dr. Grigorios I. Leontiadis
In my opinion, it is premature to change practice. For any research, and more so for systematic reviews, truth is in the details - and such details can only be assessed when the full publication is available. Based on the limited information currently available, this systematic review was been well conducted, but the quality of evidence (the trustworthiness of the results) is undermined by the characteristics of the included studies. All included studies were randomized controlled trials, but only one was at low risk for selection bias, and most of them were at high risk for detection bias. Furthermore, the generalizability to Western populations is limited because the majority of the studies were conducted in homogeneous Asian populations. Asian patients with peptic ulcer bleeding are particularly responsive to PPI treatment (Cochrane Database Syst. Rev. 2006;[1]:CD002094). Therefore, Asian studies may be more likely to show noninferiority than Western studies.

In conclusion, until the quality of the evidence can be fully assessed, it would be prudent to adhere to the recommendations from the existing practice guidelines and treat high-risk patients with peptic ulcer bleeding with high-dose intravenous infusion PPI treatment, since this is the only dose that has been proven to reduce not only rebleeding but also mortality.

Dr. Grigorios I. Leontiadis is assistant professor of medicine, division of gastroenterology, McMaster University, Hamilton, Ont. He was a consultant to a PPI manufacturer more than 5 years ago.
Body

Sachar and colleagues presented an interesting systematic review and meta-analysis at DDW 2014 (Gastroenterology 2014;146(5 Suppl 1):S-75). This presentation has fueled discussions on whether high-risk patients with peptic ulcer bleeding (those who had successful endoscopic hemostasis for high-risk stigmata) should receive PPIs intermittently (intravenously or even orally) as opposed to the current practice of high-dose continuous intravenous infusion.

Dr. Grigorios I. Leontiadis
In my opinion, it is premature to change practice. For any research, and more so for systematic reviews, truth is in the details - and such details can only be assessed when the full publication is available. Based on the limited information currently available, this systematic review was been well conducted, but the quality of evidence (the trustworthiness of the results) is undermined by the characteristics of the included studies. All included studies were randomized controlled trials, but only one was at low risk for selection bias, and most of them were at high risk for detection bias. Furthermore, the generalizability to Western populations is limited because the majority of the studies were conducted in homogeneous Asian populations. Asian patients with peptic ulcer bleeding are particularly responsive to PPI treatment (Cochrane Database Syst. Rev. 2006;[1]:CD002094). Therefore, Asian studies may be more likely to show noninferiority than Western studies.

In conclusion, until the quality of the evidence can be fully assessed, it would be prudent to adhere to the recommendations from the existing practice guidelines and treat high-risk patients with peptic ulcer bleeding with high-dose intravenous infusion PPI treatment, since this is the only dose that has been proven to reduce not only rebleeding but also mortality.

Dr. Grigorios I. Leontiadis is assistant professor of medicine, division of gastroenterology, McMaster University, Hamilton, Ont. He was a consultant to a PPI manufacturer more than 5 years ago.
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Oral PPIs for acute peptic ulcer bleeding: Not quite ready for prime time
Oral PPIs for acute peptic ulcer bleeding: Not quite ready for prime time

CHICAGO – Oral proton pump inhibitor therapy on the medical ward following endoscopic treatment of patients with a bleeding ulcer is equally effective as the current guideline-recommended practice of administering a PPI bolus followed by a 72-hour continuous intravenous infusion – and a lot less resource intensive.

That’s the highly practical message from a meta-analysis of randomized trials addressing the issue that Dr. Hamita Sachar presented at the annual Digestive Disease Week.

Dr. Hamita Sachar

Current national and international guidelines recommend an intravenous 80-mg bolus of PPI followed by a 72-hour infusion at 8 mg/hr after successful endoscopic therapy of a high-risk bleeding ulcer. These guidelines need to be revisited in light of the new data, according to Dr. Sachar, a fellow in digestive diseases at Yale University, New Haven, Conn.

"This is practice changing. Intermittent oral therapy is less expensive. Also, it’s quite easy to administer. If you can get away with twice-daily oral dosing, it’s preferred over an IV infusion by patients, it requires less nursing time, and there’s less pharmacy personnel time. As long as patients don’t have nausea and vomiting, I think it’s reasonable for them to get oral therapy because equivalent doses of IV and oral drug have exactly the same pharmacokinetic profiles," she said in an interview.

The meta-analysis, which featured a noninferiority design, included a dozen randomized trials totaling more than 1,600 patients. The primary outcome was the rate of rebleeding within 7 days. It turned out to be virtually identical in the two groups.

Moreover, there was no significant difference between patients who received intermittent oral PPI therapy at standard doses and those who got the guideline-recommended bolus, continuous-infusion regimen in terms of any of the secondary endpoints in the meta-analysis, which included rebleeding within 30 days, rebleeding within 3 days, need for blood transfusion, urgent surgical or endoscopic interventions, and length of hospital stay.

Dr. Sachar and her coinvestigators performed the meta-analysis because their physiologic model suggested that intravenous therapy was safely avoidable. They noted that several randomized trials in the literature concluded that the two treatment strategies might yield comparable outcomes; however, the individual studies were too small to allow any firm conclusions to be drawn.

The study was supported by institutional funds. Dr. Sachar reported having no financial conflicts regarding this study.

bjancin@frontlinemedcom.com

CHICAGO – Oral proton pump inhibitor therapy on the medical ward following endoscopic treatment of patients with a bleeding ulcer is equally effective as the current guideline-recommended practice of administering a PPI bolus followed by a 72-hour continuous intravenous infusion – and a lot less resource intensive.

That’s the highly practical message from a meta-analysis of randomized trials addressing the issue that Dr. Hamita Sachar presented at the annual Digestive Disease Week.

Dr. Hamita Sachar

Current national and international guidelines recommend an intravenous 80-mg bolus of PPI followed by a 72-hour infusion at 8 mg/hr after successful endoscopic therapy of a high-risk bleeding ulcer. These guidelines need to be revisited in light of the new data, according to Dr. Sachar, a fellow in digestive diseases at Yale University, New Haven, Conn.

"This is practice changing. Intermittent oral therapy is less expensive. Also, it’s quite easy to administer. If you can get away with twice-daily oral dosing, it’s preferred over an IV infusion by patients, it requires less nursing time, and there’s less pharmacy personnel time. As long as patients don’t have nausea and vomiting, I think it’s reasonable for them to get oral therapy because equivalent doses of IV and oral drug have exactly the same pharmacokinetic profiles," she said in an interview.

The meta-analysis, which featured a noninferiority design, included a dozen randomized trials totaling more than 1,600 patients. The primary outcome was the rate of rebleeding within 7 days. It turned out to be virtually identical in the two groups.

Moreover, there was no significant difference between patients who received intermittent oral PPI therapy at standard doses and those who got the guideline-recommended bolus, continuous-infusion regimen in terms of any of the secondary endpoints in the meta-analysis, which included rebleeding within 30 days, rebleeding within 3 days, need for blood transfusion, urgent surgical or endoscopic interventions, and length of hospital stay.

Dr. Sachar and her coinvestigators performed the meta-analysis because their physiologic model suggested that intravenous therapy was safely avoidable. They noted that several randomized trials in the literature concluded that the two treatment strategies might yield comparable outcomes; however, the individual studies were too small to allow any firm conclusions to be drawn.

The study was supported by institutional funds. Dr. Sachar reported having no financial conflicts regarding this study.

bjancin@frontlinemedcom.com

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Oral PPI therapy gets nod following bleeding ulcer repair
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Oral proton pump inhibitor therapy, medical ward, following endoscopic treatment, bleeding ulcer, guideline-recommended practice, administering a PPI bolus, 72-hour continuous intravenous infusion, Dr. Hamita Sachar, annual Digestive Disease Week, Intermittent oral therapy,
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Oral proton pump inhibitor therapy, medical ward, following endoscopic treatment, bleeding ulcer, guideline-recommended practice, administering a PPI bolus, 72-hour continuous intravenous infusion, Dr. Hamita Sachar, annual Digestive Disease Week, Intermittent oral therapy,
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Major finding: Oral proton pump inhibitor therapy can safely and effectively replace the guideline-recommended standard regimen consisting of a PPI bolus followed by 72 hours of continuous intravenous infusion after endoscopic treatment of a bleeding ulcer.

Data source: This was a meta-analysis with a noninferiority design. It included 12 randomized trials totaling 1,653 patients who had undergone endoscopic hemostasis for a bleeding ulcer.

Disclosures: The study was supported by institutional funds. Dr. Sachar reported having no financial conflicts regarding this study.