Superiority of lansoprazole vs ranitidine in healing nonsteroidal anti-inflammatory drug-associated gastric ulcers: results of a double-blind, randomized, multicenter study. NSAID-Associated Gastric Ulcer Study Group.

BACKGROUND: The usefulness of nonsteroidal anti-inflammatory drugs (NSAIDs) is limited by adverse gastrointestinal tract events. OBJECTIVE: To identify the optimal antisecretory therapy for healing of gastric ulcer in patients using NSAIDs and the impact of concurrent Helicobacter pylori infection on ulcer healing. DESIGN: Prospective, double-blind, multicenter, parallel-group study. SETTING: Gastroenterology practices in ambulatory and referral center settings. PATIENTS: Three hundred fifty-three patients with an active, nonmalignant gastric ulcer at least 5 mm in diameter confirmed by endoscopy and biopsy and who continued to receive stable doses of NSAIDs. INTERVENTION: Patients were randomized to receive ranitidine hydrochloride, 150 mg twice daily, or lansoprazole, 15 mg or 30 mg once daily, for 8 weeks. MEASUREMENTS: Healing was assessed by endoscopy at 4 and 8 weeks in an intent-to-treat population. Helicobacter pylori status was assessed by histological examination. RESULTS: After 8 weeks of treatment, healing was observed in 61 (53%) of 115, 81 (69%) of 118, and 85 (73%) of 117 patients receiving ranitidine lansoprazole, 15 mg, and lansoprazole, 30 mg, respectively (P<.05 for ranitidine vs both lansoprazole doses; 95% confidence interval, 3.2-28.0 for ranitidine vs lansoprazole, 15 mg, and 7.4-31.8 for ranitidine vs lansoprazole, 30 mg). The gastric ulcer healing rates were similar between H pylori-infected and -noninfected patients, with a statistically significant increase with the use of lansoprazole vs ranitidine. CONCLUSIONS: In patients who require continuous treatment with NSAIDs, lansoprazole is superior to ranitidine for healing of NSAID-associated gastric ulcers. Healing is not delayed by the presence of H pylori infection.

Immunoreactive somatostatin in human pancreatic secretion.

Somatostatin in human pancreatic juice collected during endoscopic retrograde cholangiopancreatography following secretin injection was determined by RIA. The mean immunoreactive somatostatin (IRS) levels in the pancreatic juice of 13 non-diabetics was 78 +/- 11 (SE) pg/ml. The IRS levels in 4 non-insulin-dependent diabetics ranged from 843 to 2286 pg/ml with a mean of 1559 +/- 392 (SE) pg/ml. This was significantly greater than non-diabetic values. The IRS in the pancreatic juice was immunologically indistinguishable from somatostatin14 but consisted of 2 major components, one corresponding to somatostatin14 and the other being of a molecular size of approximately 3000 daltons.

Comparison of the upper gastrointestinal safety of Arthrotec 75 and nabumetone in osteoarthritis patients at high risk for developing nonsteroidal anti-inflammatory drug-induced gastrointestinal ulcers.

A 6-week, multicenter, double-masked, placebo-controlled, parallel-group study compared the upper gastrointestinal (UGI) safety of Arthrotec 75 (diclofenac sodium 75 mg-misoprostol 200 microg; G.D. Searle & Co., Skokie, Illinois) administered twice daily with that of nabumetone 1500 mg administered once daily in 1203 patients with symptomatic osteoarthritis (OA) of the hip or knee. All patients had a documented clinical history of endoscopically confirmed gastric, pyloric-channel, or duodenal ulcer or > or = 10 erosions in the stomach or duodenum. UGI endoscopy was performed at baseline and again at week 6 or early withdrawal. Treatment with Arthrotec 75 resulted in a significantly lower combined incidence of endoscopically confirmed gastric and duodenal ulcers compared with nabumetone (4% vs 11%), and its rate of endoscopically confirmed ulceration was equivalent to that of placebo. The incidence of gastric ulcers alone was also significantly lower with Arthrotec 75 than with nabumetone (1% vs 9%). The incidence of duodenal ulcer with Arthrotec 75 was not significantly different from that with nabumetone (4% vs 3%). Types of adverse events were similar for all treatment groups, with GI adverse events predominating. Arthrotec 75 was well tolerated by the majority of patients. The results of this study demonstrate that Arthrotec 75 has a superior UGI safety profile, causing significantly fewer UGI ulcers, in comparison with nabumetone in patients with symptomatic OA and a documented history of ulcers or > or = 10 erosions.

Prevalence and cost of hospitalization for gastrointestinal complications related to peptic ulcers with bleeding or perforation: comparison of two national databases.

The purpose of this study was to determine the prevalence and cost of hospitalization for upper gastrointestinal complications, including peptic ulcers with hemorrhage or perforation. Upper gastrointestinal complications and corresponding economic data were obtained from two sources. The first was a 20% sample of all community hospital discharges (about 6 million per year) from 11 states for 1991 and 1992 Hospital Cost Utilization Project; HCUP-3). The second source of data was a claims database for employees of large US corporations and their dependents for 1992, 1993, and 1994 (about 3.5 million covered lives per year; MarketScan). A group of ICD-9 codes for the diagnosis of peptic and gastroduodenal ulcers with bleeding or perforation were used to identify hospital admissions because of upper gastrointestinal complications. Similar patterns were observed across the MarketScan and HCUP-3 databases regarding hospitalization with diagnoses related to gastrointestinal complications identified according to the ICD-9 codes. The average age of patients with upper gastrointestinal complications was 66 years in the HCUP-3 database and 52 years in the MarketScan database. The average annual rates of upper gastrointestinal complications as a primary or secondary diagnosis were 6.4 and 6.7 per 1000 discharges for 1991 and 1992, respectively (HCUP-3), and 4.3, 4.2, and 4.9 per 1000 admissions for 1992, 1993, and 1994, respectively (MarketScan). The average length of stay for upper gastrointestinal complications as a primary diagnosis was 7.8 days in 1991 and 7.5 days in 1992 (HCUP-3) and 6.1, 5.1, and 5.1 days in 1992, 1993, and 1994, respectively (MarketScan). The national average total charge for hospitalization for gastrointestinal problems as a primary diagnosis was $12,970 in 1991 and $14,294 in 1992 (HCUP-3). The average total reimbursement for hospitalizations related to upper gastrointestinal problems was $15,309 in 1992, $12,987 in 1993, and $13,150 in 1994 (MarketScan). Hospital admissions for upper gastrointestinal complications are expensive. The rate and cost per admission are higher for the older population. The results on the elements covered by both databases are consistent. Therefore the databases complement each other on the type of information abstracted.

Prevention and treatment of ulcers induced by nonsteroidal anti-inflammatory drugs: an update.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are most frequently used for the treatment of rheumatic disease due to their anti-inflammatory and analgesic properties. All NSAIDs have the potential to cause damage to the gastrointestinal (GI) tract and have been associated with the induction of peptic ulcers and massive life-threatening bleeding. The therapeutic approaches for the treatment and prevention of NSAID-induced ulcers is critically reviewed using data derived from carefully controlled, world-wide clinical studies with anti-ulcer drugs. Histamine (H2) antagonists, omeprazole, sucralfate and E-prostaglandin (PGE) analogs are effective for the treatment of NSAID-induced gastric and duodenal ulcers, if NSAIDs are discontinued. However, if NSAIDs are continued while GI damage is present, the PGE analogs misoprostol, arbaprostil and enprostil have shown efficacy in healing NSAID-induced ulcers. Furthermore, one limited clinical study demonstrated that omeprazole has efficacy in healing NSAID-associated ulcers. Neither H2 antagonists, sucralfate and sulglycotide (a cytoprotective drug) have shown efficacy in preventing NSAID-induced gastric ulcers. However H2 antagonists have shown efficacy in preventing NSAID-induced duodenal ulcers. In contrast, only misoprostol prevents the development of NSAID-induced gastric and duodenal ulcers. Such pharmacological observations suggest that the pathophysiologic mechanisms for the induction of NSAID-induced gastric ulcer are distinctly different from those of NSAID-induced duodenal ulcers. Mild diarrhea and GI intolerance were the predominant adverse reactions experienced by patients receiving synthetic PGEs, particularly enprostil and arbaprostil. From the published data, we conclude that misoprostol is the only anti-ulcer drug proven to be well tolerated and effective for the treatment and prevention of NSAID-induced gastric and duodenal ulcers in patients receiving chronic NSAIDs therapy.

Treatment and prevention of nonsteroidal anti-inflammatory drug induced gastrointestinal mucosal injury.

It is generally recognized that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) can cause varying degrees of gastroduodenal mucosal damage. These agents are most frequently used by physicians for rheumatic diseases because of their high effectiveness in reducing joint pain and swelling. Four classes of drugs, namely histamine (H2) blockers, antacids, sucralfate and prostaglandins are available for treatment of gastric mucosal damage caused by NSAIDs. All these drugs are very effective in healing gastric and duodenal injury if nonsteroidal anti-inflammatory drugs are discontinued. However, current data suggest that if nonsteroidal anti-inflammatory drugs are continued while gastrointestinal damage is present there may be significant differences among these drugs in healing of gastric mucosal damage. Synthetic prostaglandins are therapeutically superior over other forms of treatment when nonsteroidal anti-inflammatory drugs are continued in the presence of gastric mucosal injury. This article is a review of such data from the literature for a) the treatment and b) the prevention of gastrointestinal damage due to aspirin and nonsteroidal anti-inflammatory drugs.

Protective effects of prostaglandins against nonsteroidal anti-inflammatory drug-induced gastrointestinal mucosal injury.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are an integral part of the therapy of rheumatic diseases. All NSAIDs have the potential to cause damage to the gastrointestinal (GI) tract and have been implicated as a cause of peptic ulceration and massive life-threatening bleeding, often without warning symptoms. The basis of the damaging actions of NSAIDs on the GI tract is believed to be a consequence of two events: depletion of endogenous prostaglandins (PGs) and a direct damaging action on the mucosal integrity. Current evidence indicates that PGs play an important role in maintaining the integrity of the GI tract against ulcerogenic stimuli and are therefore ideally suited to counteract the NSAID-induced deleterious actions on the mucosa. With the exception of synthetic prostaglandins, the current therapeutic interventions used for the treatment of NSAID injury are not ideal. Misoprostol, a synthetic E-prostaglandin analogue, has been found to prevent and heal GI lesions induced by NSAIDs. The basis for the protective effect of prostaglandins is a consequence of their gastric antisecretory and mucosal protective properties. The mucosal protective effects of misoprostol are multifactorial and include, in part, the stimulation of mucus and bicarbonate secretion, an increased or sustained mucosal blood flow and the stabilization of the barrier function of the stomach. Misoprostol represents a major new advance in our therapeutic armamentarium for the treatment and prevention of NSAID-induced GI mucosal injury.

Prevention of gastrointestinal complications associated with nonsteroidal antiinflammatory drugs.

Nonsteroidal antiinflammatory drugs (NSAID), although used frequently for the treatment of arthritis and musculoskeletal disorders, may produce deleterious effects related to the gastrointestinal (GI) tract, including dyspeptic symptoms, erosions, ulcers, and serious GI complications (i.e., bleeding, perforation, and gastric outlet obstruction). Endoscopic studies with the synthetic prostaglandin E1 analog misoprostol, various acid-reducing agents (e.g., H2 receptor antagonists and proton pump inhibitors), and surface-active drugs such as sucralfate, have been shown to prevent NSAID induced gastric and/or duodenal ulcers. The Misoprostol Ulcer Complication Outcomes Safety Assessment (MUCOSA) trial was a 6 month, randomized, double blind, placebo controlled study to investigate whether concurrent administration of misoprostol would significantly reduce the occurrence of serious upper GI complications in patients with rheumatoid arthritis (RA) who were receiving NSAID. Results showed that overall complications were reduced by 40% (p = 0.049) among patients receiving misoprostol (25 patients with definite serious GI events among 4404 patients treated) compared with those receiving placebo (42 out of 4439 patients). Thus, cotherapy with misoprostol resulted in a statistically significant reduction in the incidence of serious NSAID induced upper GI complications compared with placebo in patients with RA.

Treatment and prevention of NSAID induced gastroduodenal mucosal damage.

The use of aspirin and other nonsteroidal antiinflammatory drugs (NSAID) is associated with various degrees of gastroduodenal damage. The agents currently available for the treatment of NSAID induced gastric mucosal damage are histamine2-receptor antagonists, antacids, sucralfate and prostaglandin (PG) analogs. Although all of these agents are effective in healing gastric and duodenal injury if NSAID therapy is discontinued, currently available data suggest that there may be significant differences among these drugs in healing or preventing mucosal injury when NSAID therapy is continued. In particular, the synthetic PG misoprostol appears to be therapeutically superior to agents in the other drug classes in these settings.

Options in the treatment and prevention of NSAID-induced gastroduodenal mucosal damage.

Aspirin and other nonsteroidal antiinflammatory drugs (NSAID) have been associated with various degrees of gastroduodenal damage. The agents currently available for the treatment of gastric mucosal damage caused by NSAID are histamine2-receptor antagonists, antacids, sucralfate and prostaglandins. Although all of these agents are effective in healing gastric and duodenal injury if NSAID are discontinued, currently available data suggest that there may be significant differences among these drugs in healing gastric mucosal injury if NSAID are continued in the presence of such injury. In particular, the synthetic prostaglandin misoprostol appears to be therapeutically superior to agents in the other drug classes in such a context. Reviewed herein are data from the literature on both treatment and prevention of gastrointestinal damage due to NSAIDs.

Epidemiology and prevention of non-steroidal anti-inflammatory drug effects in the gastrointestinal tract.

Lesions of the gastric, duodenal and intestinal mucosae are found in large numbers of patients using non-steroidal anti-inflammatory drugs (NSAIDs); however, no markers have yet been isolated to identify patients at risk for developing gastrointestinal problems or to predict which patients with lesions are at risk for developing catastrophic complications. There appears to be a poor correlation between the presence of ulcer disease and the appearance of symptoms while patients are using NSAIDs. The ideal treatment--namely, withdrawal from NSAIDs--may not always be practicable in patients who require the analgesic benefit of these otherwise generally innocuous agents. It is incumbent on the clinician to identify the agent most appropriate for the needs of the individual, and to supplement NSAID therapy, where appropriate, with a means of preventing or minimizing adverse effects. Four classes of drugs are used to prevent NSAID-related gastric mucosal damage: histamine (H2)-receptor antagonists (ranitidine, cimetidine, nizatidine, famotidine); gastric acid-pump inhibitor (omeprazole); barrier agent (sucralfate); and prostaglandin analogue (misoprostol). The current therapies (H2 antagonists and barriers) have not lived up to their promise for preventing gastroduodenal erosion. Moreover, such protection as they provide is limited to the duodenal mucosa; they afford no protection to the gastric mucosa. Preliminary data indicate that an acid pump inhibitor may be useful, but large-scale studies have yet to be reported. Acute and long-term studies of the prostaglandin analogue misoprostol have shown that this agent has an important role as an adjunctive therapy to prevent both gastric and duodenal ulceration due to NSAIDs.

Making sense of NSAID gastropathy and considering the therapeutic options.

There is increasing recognition that nonsteroidal anti-inflammatory drugs (NSAIDs), while quite effective in treating arthritic symptoms, are associated with gastrointestinal mucosal damage. Although therapy for patients with NSAID-induced ulcers or those at high risk of developing them is still a matter of debate, the current literature supports the use of misoprostol as the only drug effective for the prevention of both NSAID-induced gastric and duodenal ulceration. It has also been shown to treat NSAID-induced gastropathy in patients continuing their NSAID therapy. In a study of misoprostol (100 or 200 micrograms QID) plus NSAID, after three months of continuous therapy, a significantly lower frequency of gastric ulcers in the misoprostol-treated group was revealed: 100 micrograms misoprostol, 5.6%; 200 micrograms misoprostol, 1.4%; placebo, 21.7%. A recent three-month, placebo-controlled study established the efficacy of misoprostol 200 micrograms QID in the prevention of NSAID-induced duodenal ulcers in 429 patients with osteoarthritis (OA), rheumatoid arthritis (RA), or other rheumatic disease, who were receiving daily treatment with various NSAIDs. The incidence of duodenal ulcer development over three months was 1.0% in patients treated with misoprostol versus 6.3% in placebo-treated patients (P = 0.004). The same trial also evaluated the efficacy of misoprostol 200 micrograms QID versus placebo in preventing NSAID-induced gastric ulcers. The incidence of gastric ulcer over the three-month treatment period was 1.5% in patients treated with misoprostol versus 9.0% in placebo-treated patients (P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-inflammatories and gastroduodenal damage: therapeutic options.

The association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the development of upper gastrointestinal (GI) damage is well established. Studies have indicated that 12-30% of NSAID users will develop gastric ulcers and that 2-19% will develop duodenal ulcers. Furthermore, many NSAID-induced ulcers are "silent" and are only discovered when complications occur. When possible, the most effective method of preventing NSAID-induced gastropathy is discontinuation of NSAIDs or a reduction in the NSAID dosage. For patients who require continued NSAID therapy, four classes of drugs have been evaluated for their potential protective effects against NSAID-induced gastroduodenal damage:H2-receptor antagonists (eg, ranitidine), proton pump inhibitors (eg, omeprazole), acid-barrier compounds (eg, sucralfate), and prostaglandin E1 analogues (eg, misoprostol). H2-receptor antagonists have not been shown to be effective in preventing NSAID-induced gastric ulcers, and sucralfate has not been shown to be effective in preventing NSAID-induced gastric or duodenal ulcers. Similarly, newer proton pump inhibitors, such as omeprazole, do not appear to protect the stomach against NSAID-induced damage. In contrast, misoprostol has proven its efficacy in preventing both gastric and duodenal ulcers in arthritis patients taking NSAID therapy.

Selective COX-2 inhibitors and gastrointestinal mucosal injury: pharmacological and therapeutic considerations.

It is well recognized that nonsteroidal antiinflammatory drugs (NSAIDs) induce gastrointestinal (GI) ulcerations, perforation and bleeding, which clearly limit their therapeutic value. The recent introduction of NSAIDs with selective cyclooxygenase-2 (COX-2) inhibitory effect is a major pharmacologic milestone in therapeutics. Selective COX-2 inhibitors exhibit considerable dissociation between their antiinflammatory/analgesic action and their GI toxicity. However, from a therapeutic consideration, there are still several unresolved and confusing issues with these drugs such as: the pharmacologic classification of the COX-2 selectivity; therapeutic value as antirheumatic/analgesic drugs; potential toxicity in patients at risk for the development of ulcer-related complications or patients with inflammatory bowel disease and potential renal toxicity. Although existing clinical efficacy studies with celecoxib and rofecoxib, two selective COX-2 inhibitors, were associated with considerably lower ulcerogenic rates when compared with nonselective NSAIDs, there are no long term outcome studies with these drugs similar to the MUCOSA trial performed with misoprostol. Furthermore, the selectivity of COX-2 inhibitors appears to be specific to the stomach and duodenum but not the kidney. While awaiting additional long term studies with selective COX-2 inhibitors, we recommend instituting prophylactic therapy with misoprostol in patients at risk for the development of ulcer related complications. In conclusion, we believe that the introduction of selective COX-2 inhibitors will revolutionize the treatment of pain and inflammation. However, additional basic and clinical studies are required to address the pharmacologic and therapeutic uncertainties for this class of drugs.

Prevention of nonsteroidal anti-inflammatory drug-induced gastroduodenal ulcers: role of mucosal protective and gastric antisecretory drugs.

One of the most serious side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) is upper gastrointestinal mucosal damage that may result in erosions, ulcerations and other serious complications. NSAIDs reduce endogenous prostaglandins, and this reduction is relevant to their pharmacology and toxicity. The stomach and to some extent the duodenum are the major organs involved in the mucosal toxicity of NSAIDs. With the availability of the synthetic prostaglandin misoprostol, it has become possible to prevent NSAID-induced gastroduodenal ulcers without compromising the beneficial antirheumatic and analgesic effects of NSAID therapy. In fact, misoprostol is the only drug with established long-term efficacy in preventing NSAID-induced gastroduodenal ulcers in rheumatic patients. The purpose of this communication is to critically review the efficacy of gastric antisecretory drugs, mucosal protective drugs and misoprostol when used for the prevention of NSAID-induced ulcers, considering only data from well-controlled, randomized, double-blind clinical studies. The histamine H2-receptor antagonist ranitidine has been shown to be effective in preventing NSAID-induced duodenal ulcers, but has no efficacy in preventing NSAID-induced gastric ulcers. In a direct comparative trial with ranitidine, misoprostol (200 micrograms qid) was significantly more effective than ranitidine (150 mg bid) in preventing gastric ulcers in chronic NSAID users. The inactivity of ranitidine in preventing gastric ulcers indicates that the pathogenesis of NSAID-induced gastric ulcers is not related to gastric acid. Limited but conflicting data exist with omeprazole. The mucosal-coating drug sucralfate has not been found effective in preventing NSAID ulcers. In fact, in a direct comparative trial, misoprostol (200 micrograms qid) was significantly more effective than sucralfate (1 g qid) in preventing gastric ulcers in patients receiving chronic NSAID therapy. No meaningful data exist with organic bismuth salts, a group of drugs which has mucosal coating and protective properties. From this brief overview, we conclude: (1) mucosal-coating compounds have no therapeutic role in preventing NSAID-induced ulceration; (2) gastric antisecretory drugs are not effective in preventing NSAID-induced gastric ulcers, and (3) misoprostol is the only antiulcer drug proven to be effective for preventing NSAID-induced gastric and duodenal ulcers in patients receiving chronic NSAID. Misoprostol represents a major therapeutic advance for the management of NSAID-induced mucosal injury.

Gastric erosions induced by nonsteroidal anti-inflammatory drugs: clinical significance, pathogenesis, and therapeutic perspectives.

The development of ulceration and ulcer complications by nonsteroidal anti-inflammatory drugs (NSAIDs) is now well established. Gastric erosions occur in about 60% of patients receiving long-term NSAID therapy. Many clinicians consider such erosions benign in nature and not requiring therapeutic intervention. Recent evidence, however, indicates that gastric erosions predispose rheumatic patients to frank ulcerations and ulcer complications. This brief overview summarizes the clinical dilemma in the diagnosis and treatment of NSAID-induced gastric erosions. Current data suggest that misoprostol has important therapeutic benefits for the treatment and prevention of gastric erosions in patients receiving long-term NSAID therapy.

Prevention and treatment of ulcers induced by nonsteroidal anti-inflammatory drugs.

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) can cause varying degrees of gastroduodenal mucosal damage. These agents are most frequently used for the treatment of rheumatic diseases because they are highly effective in reducing joint pain and swelling. Histamine H2-receptor antagonists, omeprazole, sucralfate, and misoprostol are drugs available for the treatment of gastric mucosal damage caused by NSAIDs. In controlled clinical studies, all these drugs effectively heal gastric and duodenal injury if NSAIDs are discontinued. However, current data suggest that if NSAIDs are continued while gastrointestinal damage is present, only misoprostol and omeprazole have demonstrated efficacy in healing gastric mucosal injury. Misoprostol also effectively heals NSAID-induced duodenal injury. At this time, no data exist on the efficacy of other antiulcer drugs in healing duodenal erosions or ulceration if NSAID administration is continued. Regarding prevention of NSAID-induced gastric ulcer, controlled clinical studies with H2 antagonists and sucralfate have failed to show any therapeutic benefit. Ranitidine, however, has shown efficacy in preventing NSAID-induced duodenal ulcers. The coadministration of misoprostol with NSAIDs to patients who have either osteoarthritis or rheumatoid arthritis prevents the development of gastric and duodenal ulcers. Based on current published information, this property distinguishes misoprostol from other antiulcer drugs.

Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial.

A double-blind, placebo-controlled study was carried out to see whether the synthetic E prostaglandin, misoprostol, would prevent gastric ulcer induced by non-steroidal anti-inflammatory drugs (NSAIDs). 420 patients with osteoarthritis and NSAID-associated abdominal pain were studied; they were receiving ibuprofen, piroxicam, or naproxen. Endoscopy was done at entry and after 1, 2, and 3 months of continuous treatment with 100 micrograms or 200 micrograms misoprostol or placebo, given four times daily with meals and at bedtime, concurrently with the NSAID. Abdominal pain was rated independently by patients and physicians. A treatment failure was defined as development of a gastric ulcer. Gastric ulcers (0.3 cm in diameter or greater) occurred less frequently (p less than 0.001) in both misoprostol treatment groups (5.6% 100 micrograms and 1.4% 200 micrograms) than in the placebo group (21.7%). The significant difference in ulcer formation between the placebo and the misoprostol treatment groups remained when comparisons were restricted to ulcers greater than 0.5 cm in diameter (12.3% placebo, 4.2% 100 micrograms misoprostol, and 0.7% 200 micrograms misoprostol). Mild to moderate, self-limiting diarrhoea was the most frequently reported adverse effect attributed to misoprostol. These results provide the first clear indication that NSAID-induced ulcers are preventable.

Prostaglandins: an overview of the worldwide clinical experience.

Synthetic prostaglandins of the E series have cytoprotective and gastric antisecretory actions. Both actions are relevant to their therapeutic usefulness in treating and preventing gastrointestinal mucosal diseases. Controlled clinical studies have shown prostaglandins to be effective treatment for gastric and duodenal ulcer disease. Although used widely in dozens of foreign countries, however, prostaglandins have not been approved by the United States Food and Drug Administration for use in the treatment of peptic ulcer disease. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased incidence of gastric and duodenal ulcers, gastrointestinal bleeding, and increased morbidity and mortality. Misoprostol, a prostaglandin E1 analogue, is effective in preventing and treating NSAID-induced mucosal damage and has been approved by the Food and Drug Administration for the prevention of NSAID-associated gastric ulcers. Controlled studies have not provided convincing evidence that H2-receptor antagonists or sucralfate prevents NSAID-induced gastric ulcer. Preliminary clinical studies indicate that some E-prostaglandins may also be effective in treating and/or preventing stress ulcer, cystic fibrosis, and hepatorenal syndrome and in improving graft survival in renal transplant patients receiving cyclosporine. Additionally, in vitro and animal studies suggest that prostaglandins may have therapeutic value in inflammatory bowel disease, and they may promote cartilage repair by an inhibitory action on interleukin-1. The latter finding could be of major relevance in preventing cartilage destruction in rheumatic patients. Significant side effects associated with the clinical use of prostaglandins include mild to moderate diarrhea and stimulation of uterine contraction during early pregnancy. Prostaglandins are effective for the treatment of peptic ulcer disease and, to date, are the only effective therapy for preventing the total spectrum of NSAID-induced mucosal damage. These compounds may also prove effective in treating various inflammatory disorders.

Nonsteroidal anti-inflammatory drugs and acute upper gastrointestinal bleeding: a prospective study.

One of the most serious side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) is upper gastrointestinal mucosal damage that may result in hemorrhage, perforation, or even death. To determine the association between NSAID ingestion and acute upper gastrointestinal bleeding, we prospectively evaluated all hospitalized patients who underwent upper endoscopy for hematemesis and/or melena over a 12-month period at the Veterans Administration Medical Center of New Orleans and Tulane Medical Center. Forty of the 139 patients (29%) at the Veterans Administration Medical Center and 21 of the 90 patients (23%) at Tulane Medical Center were using NSAIDs at the time of referral for endoscopy. Erosive gastritis was the most common cause of bleeding attributed to NSAIDs (P less than .005). Seventy percent of the patients with acute upper gastrointestinal bleeding who used NSAIDs were over age 55, compared with 55% of patients not using NSAIDs (P less than .05). This study indicates that NSAID use is found in 27% of hospitalized patients presenting with acute upper gastrointestinal bleeding. Future prospective studies are needed to establish whether prophylactic therapy with synthetic prostaglandins may affect the prevalence of upper gastrointestinal bleeding in patients using NSAIDs.