Peptic ulcers, often due to
Helicobacter pylori
or the use of nonsteroidal antiinflammatory drugs (NSAIDs), commonly cause upper gastrointestinal bleeding. Endoscopic therapy, proton-pump inhibitors, ...therapy for
H. pylori
infection, and nonuse of NSAIDs are described.
Foreword
This
Journal
feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author’s clinical recommendations.
Stage
A 55-year-old woman presents to the emergency department at 11:30 p.m. with hematemesis. She is otherwise healthy and has no risk factors for liver disease. Her only medication is aspirin (at a dose of 81 mg daily), which she started to take 6 months ago after reading that it reduces the risk of heart disease. The blood pressure is 94/60 mm Hg, and the heart rate is 108 beats per minute; the physical examination is otherwise normal. The hemoglobin level is 11.0 g per deciliter, platelet count 220,000 per cubic millimeter, international normalized ratio 1.0, and blood urea nitrogen . . .
AbstractUpper gastrointestinal bleeding (UGIB) is a common medical emergency, with a reported mortality of 2-10%. Patients identified as being at very low risk of either needing an intervention or ...death can be managed as outpatients. For all other patients, intravenous fluids as needed for resuscitation and red cell transfusion at a hemoglobin threshold of 70-80 g/L are recommended. After resuscitation is initiated, proton pump inhibitors (PPIs) and the prokinetic agent erythromycin may be administered, with antibiotics and vasoactive drugs recommended in patients who have cirrhosis. Endoscopy should be undertaken within 24 hours, with earlier endoscopy considered after resuscitation in patients at high risk, such as those with hemodynamic instability. Endoscopic treatment is used for variceal bleeding (for example, ligation for esophageal varices and tissue glue for gastric varices) and for high risk non-variceal bleeding (for example, injection, thermal probes, or clips for lesions with active bleeding or non-bleeding visible vessel). Patients who require endoscopic therapy for ulcer bleeding should receive high dose proton pump inhibitors after endoscopy, whereas those who have variceal bleeding should continue taking antibiotics and vasoactive drugs. Recurrent ulcer bleeding is treated with repeat endoscopic therapy, with subsequent bleeding managed by interventional radiology or surgery. Recurrent variceal bleeding is generally treated with transjugular intrahepatic portosystemic shunt. In patients who require antithrombotic agents, outcomes appear to be better when these drugs are reintroduced early.
Background Numerous agents are available for moderate sedation in endoscopy. Objective Our purpose was to compare efficacy, safety, and efficiency of agents used for moderate sedation in EGD or ...colonoscopy. Design Systematic review of computerized bibliographic databases for randomized trials of moderate sedation that compared 2 active regimens or 1 active regimen with placebo or no sedation. Patients Unselected adults undergoing EGD or colonoscopy with a goal of moderate sedation. Main Outcome Measurements Sedation-related complications, patient assessments (satisfaction, pain, memory, willingness to repeat examination), physician assessments (satisfaction, level of sedation, patient cooperation, examination quality), and procedure-related efficiency outcomes (sedation, procedure, or recovery time). Results Thirty-six studies (N = 3918 patients) were included. Sedation improved patient satisfaction (relative risk RR = 2.29, range 1.16-4.53) and willingness to repeat EGD (RR = 1.25, range 1.13-1.38) versus no sedation. Midazolam provided superior patient satisfaction to diazepam (RR = 1.18, range 1.07-1.29) and less frequent memory of EGD (RR = 0.57, range 0.50-0.60) versus diazepam. Adverse events and patient/physician assessments were not significantly different for midazolam (with or without narcotics) versus propofol except for slightly less patient satisfaction (RR = 0.90, range 0.83-0.97) and more frequent memory (RR = 3.00, range 1.25-7.21) with midazolam plus narcotics. Procedure times were similar, but sedation and recovery times were shorter with propofol than midazolam-based regimens. Limitations Marked variability in design, regimens tested, and outcomes assessed; relatively poor methodologic quality (Jadad score ≤3 in 23/36 trials). Conclusions Moderate sedation provides a high level of physician and patient satisfaction and a low risk of serious adverse events with all currently available agents. Midazolam-based regimens have longer sedation and recovery times than does propofol.
The community of microorganisms within the human gut (or microbiota) is critical to health and functions with a level of complexity comparable to that of an organ system. Alterations of this ecology ...(or dysbiosis) have been implicated in a number of disease states, and the prototypical example is Clostridium difficile infection (CDI). Fecal microbiota transplantation (FMT) has been demonstrated to durably alter the gut microbiota of the recipient and has shown efficacy in the treatment of patients with recurrent CDI. There is hope that FMT may eventually prove beneficial for the treatment of other diseases associated with alterations in gut microbiota, such as inflammatory bowel disease, irritable bowel syndrome, and metabolic syndrome, to name a few. Although the basic principles that underlie the mechanisms by which FMT shows therapeutic efficacy in CDI are becoming apparent, further research is needed to understand the possible role of FMT in these other conditions. Although relatively simple to perform, questions regarding both short-term and long-term safety as well as the complex and rapidly evolving regulatory landscape has limited widespread use. Future work will focus on establishing best practices and more robust safety data than exist currently, as well as refining FMT beyond current “whole-stool” transplants to increase safety and tolerability. Encapsulated formulations, full-spectrum stool-based products, and defined microbial consortia are all in the immediate future.
For decades, proton pump inhibitors (PPIs) have been the mainstay of treatment for erosive esophagitis. The potassium-competitive acid blocker vonoprazan provides more potent acid inhibition than ...PPIs, but data on its efficacy for erosive esophagitis are limited.
Adults with erosive esophagitis were randomized to once-daily vonoprazan, 20 mg, or lansoprazole, 30 mg, for up to 8 weeks. Patients with healing were rerandomized to once-daily vonoprazan, 10 mg, vonoprazan, 20 mg, or lansoprazole, 15 mg, for 24 weeks. Primary end points, percentage with healing by week 8 endoscopy, and maintenance of healing at week 24 endoscopy, were assessed in noninferiority comparisons (noninferiority margins, 10%), with superiority analyses prespecified if noninferiority was demonstrated. Analyses of primary and secondary end points were performed using fixed-sequence testing procedures.
Among 1024 patients in the healing phase, vonoprazan was noninferior to lansoprazole in the primary analysis and superior on the exploratory analysis of healing (92.9 vs 84.6%; difference, 8.3%; 95% confidence interval CI, 4.5%–12.2%). Secondary analyses showed vonoprazan was noninferior in heartburn-free days (difference, 2.7%; 95% CI, −1.6% to 7.0%), and superior in healing Los Angeles Classification Grade C/D esophagitis at week 2 (difference, 17.6%; 95% CI, 7.4%–27.4%). Among 878 patients in the maintenance phase, vonoprazan was noninferior to lansoprazole in the primary analysis and superior on the secondary analysis of maintenance of healing (20 mg vs lansoprazole: difference, 8.7%; 95% CI, 1.8%–15.5%; 10 mg vs lansoprazole: difference, 7.2%; 95% CI, 0.2%–14.1%) and secondary analysis of maintenance of healing Grade C/D esophagitis (20 mg vs lansoprazole: difference, 15.7%; 95% CI, 2.5%–28.4%; 10 mg vs lansoprazole: difference, 13.3%; 95% CI, 0.02%–26.1%).
Vonoprazan was noninferior and superior to the PPI lansoprazole in healing and maintenance of healing of erosive esophagitis. This benefit was seen predominantly in more severe erosive esophagitis. (ClinicalTrials.gov: NCT04124926).
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Novel, effective treatments for Helicobacter pylori infection are needed. This study evaluated the efficacy of vonoprazan, a potassium-competitive acid blocker, vs standard treatment on H pylori ...eradication in the United States and Europe.
In a randomized, controlled, phase 3 trial, treatment-naïve adults with H pylori infection were randomized 1:1:1 to open-label vonoprazan dual therapy (20 mg vonoprazan twice daily; 1 g amoxicillin 3 times daily), or double-blind triple therapy twice a day (vonoprazan 20 mg or lansoprazole 30 mg; amoxicillin 1 g; clarithromycin 500 mg) for 14 days. The primary outcome was noninferiority in eradication rates in patients without clarithromycin- and amoxicillin-resistant strains (noninferiority margin = 10%). Secondary outcomes assessed superiority in eradication rates in clarithromycin-resistant infections, and in all patients.
A total of 1046 patients were randomized. Primary outcome eradication rates (nonresistant strains): vonoprazan triple therapy 84.7%, dual therapy 78.5%, vs lansoprazole triple therapy 78.8% (both noninferior; difference 5.9%; 95% confidence interval CI, −0.8 to 12.6; P < .001; difference –0.3%; 95% CI, −7.4 to 6.8; P = .007, respectively). Eradication rates in clarithromycin-resistant infections: vonoprazan triple therapy 65.8%, dual therapy 69.6%, vs lansoprazole triple therapy 31.9% (both superior; difference 33.9%; 95% CI, 17.7–48.1; P < .001; difference 37.7%; 95% CI, 20.5–52.6; P < .001, respectively). In all patients, vonoprazan triple and dual therapy were superior to lansoprazole triple therapy (80.8% and 77.2%, respectively, vs 68.5%, difference 12.3%; 95% CI, 5.7–18.8; P < .001; difference 8.7%; 95% CI, 1.9–15.4; P = .013). Overall frequency of treatment-emergent adverse events was similar between vonoprazan and lansoprazole regimens (P > .05).
Both vonoprazan-based regimens were superior to proton pump inhibitor–based triple therapy in clarithromycin-resistant strains and in the overall study population. ClinicalTrials.gov; NCT04167670.
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Vonoprazan, a new type of stomach acid blocker, improves eradication of Helicobacter pylori infection compared with a proton pump inhibitor acid blocker.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are probably the most common cause of gastroduodenal injury in the United States today. Approximately half of patients who regularly take NSAIDs have ...gastric erosions, and 15%–30% have ulcers when they are examined endoscopically. However, the incidence of clinical gastrointestinal (GI) events caused by NSAIDs is much lower. Clinical upper GI events may occur in 3%–4.5% of patients taking NSAIDs, and serious complicated events develop in approximately 1.5%. However, the risk varies widely in relationship to clinical features such as history of ulcers or GI events, age, concomitant anticoagulant or steroid use, and NSAID dose. This review discusses the risks of clinical GI disease in NSAID users, the predictors of increased risk, and strategies for prevention of NSAID-associated GI disease.
GASTROENTROLOGY 2001;120:594-606
In a phase 3 trial, patients with moderately to severely active ulcerative colitis were randomly assigned to receive placebo or ozanimod, a selective sphingosine-1-phosphate receptor modulator. ...Clinical remission was significantly greater with ozanimod during the induction and maintenance periods. The incidence of infection was higher with ozanimod than with placebo during maintenance.
Current consensus recommendations state that patients prescribed clopidogrel plus aspirin should receive a proton pump inhibitor (PPI) to reduce gastrointestinal bleeding. Clopidogrel is converted to ...its active metabolite by cytochrome P450 (CYP) enzymes. Clopidogrel users with decreased CYP2C19 function have less inhibition of platelet aggregation and increased cardiovascular (CV) events. As PPI metabolism also involves CYP2C19, it was hypothesized that competition by PPIs might interfere with clopidogrel's action. Omeprazole, but not other PPIs, worsens surrogate markers of clopidogrel efficacy. Some (but not all) observational studies show that clopidogrel users prescribed PPIs have increased risks of CV events (hazard/odds ratios=1.25-1.5). When effect sizes are small to moderate (relative risks<1.5-2.0), however, it is only possible to conclude whether statistical associations are valid in randomized trials. A randomized trial of omeprazole vs. placebo in clopidogrel users showed no difference in CV events (hazard ratio=1.02,0.70-1.51). Thus, current evidence does not justify a conclusion that PPIs are associated with CV events among clopidogrel users, let alone a judgment of causality. Nonetheless, positive results from some observational studies and biological plausibility have led some health-care providers to accept that PPIs reduce clopidogrel's efficacy. The US Food and Drug Administration (FDA) recommends that "concomitant use of drugs that inhibit CYP2C19 (e.g., omeprazole) should be discouraged." As the presence of PPIs and clopidogrel in plasma is short lived, separation by 12-20 h should in theory prevent competitive inhibition of CYP metabolism and minimize any potential, though unproven, clinical interaction. PPI may be given before breakfast and clopidogrel at bedtime, or PPI may be taken before dinner and clopidogrel at lunchtime.
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