Selective inhibitors of COX-2--are they safe for the stomach?

NSAIDs are widely used and beneficial for patients with inflammatory pain. However, NSAIDs cause significant adverse upper gastrointestinal effects, including increased mortality from serious ulcer complications. NSAIDs exert their anti-inflammatory effects by inhibiting the activity of the COX enzyme, which was recently shown to exist in two isoforms, a constitutive COX-1 and an inducible COX-2. The latter isoform is induced in inflammation, while the former is responsible for prostaglandin effects on platelet function and gastric mucosal defense. Two specific COX-2 inhibitors have recently been introduced into the market. The available data from clinical trials indicate that these new drugs have anti-inflammatory and analgesic effects similar to those of conventional NSAIDs, but reduced rates of adverse upper gastroduodenal effects, which are similar to those observed with placebo. This difference in rates of adverse effects might imply improved safety for patients requiring anti-inflammatory treatment. It has, however, to be kept in mind that specific COX-2 inhibitors lack cardiovascular protective effects. Considering the high consumption rate of NSAIDs to achieve pain relief in arthritis and other musculo-sceletal diseases, the reduced risk of gastrointestinal ulcers and ulcer complications may have a positive impact on population health and health economy.     

COX-1, COX-2: so what?

The discovery of the second isoform of cycloxygenase has led to a rapid expansion in basic science, pharmacology and clinical data. With the completion of phase II studies of the new COX-2 specific inhibitors this review examines some of the implications of the new data.     

Vaccines: an ongoing promise?

Over the past decade, intensive research has focused on developing a vaccine therapy for Helicobacter pylori. Substantial unresolved questions cloud the current approach, and the development of a vaccine against this unique organism has proved very challenging. Many candidate vaccines have been tested in animal models. The immunogenicity and the safety of some vaccine formulations have been recently evaluated through clinical trials, and the efficacy of these vaccine therapies in humans will be determined in the near future. This article will provide an overview of the current knowledge of natural and vaccine-induced immune responses to H. pylori infection. It will also review past vaccine successes and failures in animal models and the limited experience to date in using vaccine therapy in humans. Several obstacles to H. pylori vaccine development efforts along with the future direction of these efforts will be discussed.     

Cardiovascular effects of selective COX-2 inhibition: is there a class effect? The International COX-2 Study Group

The International COX-2 Study Group, a panel of independent physicians and scientists, convened January 28-30, 2005, in Washington, DC, to discuss the issues concerning the cardiovascular (CV) profile of coxibs. The purpose of the meeting was to review potential mechanisms by which inhibition of COX-2 by selective and nonselective NSAID could increase risk of CV events, to evaluate the similarities and differences between drugs based on mechanism and pharmacology, and to propose potential trial methodology to more definitively answer questions regarding cardiovascular risk.     

Selective serotonin reuptake inhibitors and increased bleeding risk: are we missing something?

Purpose

Selective serotonin reuptake inhibitors (SSRIs) are first line agents to treat clinical depression. Although these medications exhibit a favorable safety profile, there are multiple case reports, registries, and uncontrolled studies suggesting that use of SSRIs might be associated in the increased risk of bleeding events. There is also emerging evidence that these side effects of SSRIs are due to blockade of serotonin reuptake in platelets and subsequent platelet dysfunction.

Methods

The analysis of evidence linking SSRIs with bleeding episodes to define the prevalence, specific clinical characteristics, and estimated risk when SSRIs are used in combination with antiplatelet agents or/and anticoagulants.

Results

There are over 120 MEDLINE-cited peer-reviewed research papers and more than 50 000 Web pages devoted to SSRI-related bleeding events.

Conclusion

Independently of the brand, use of SSRIs is indeed associated with increased bleeding risk. Although such complications are rare, their frequency is growing, and physicians should be aware of SSRI-induced hemorrhages, especially in patients with hereditary platelet defects, and those treated with antiplatelet agents. Prospective studies are urgently needed to determine whether SSRIs will yield additional bleeding risks when used long term concomitantly with aspirin or clopidogrel.     

Selective serotonin reuptake inhibitors and risk of upper GI bleeding: confusion or confounding?

Background

Selective serotonin reuptake inhibitors (SSRIs) represent a relatively new class of antidepressants. Several studies have reported bleeding disorders associated with the use of SSRIs, which are considered the result of a decrease in platelet serotonin leading to a defect in platelet aggregation. To what extent the use of SSRIs increases the risk of gastrointestinal bleeding is unclear.

Methods

A comprehensive literature search for studies addressing SSRI use and upper gastrointestinal tract bleeding (UGIB) was conducted using Medline, EMBASE, and Cochrane databases with a recursive manual reference search up to May 2005. Any observational and interventional studies were systematically reviewed, and critical appraisal was conducted on available studies.

Results

Published clinical evidence on the relationship between SSRI use and gastrointestinal bleeding is limited to observational studies without any clinical trials. Three cohort studies and one case-control study met inclusion criteria. These studies combined different affinity SSRIs in the class and had differing control groups with conflicting conclusions. Both a cohort study and a case-control study investigating the concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin found that combined use with an SSRI increased the risk of UGIB.

Conclusions

Only a few epidemiology studies have investigated the association between SSRIs and UGIB. They provide weak evidence to support the hypothesis of a link between SSRIs and UGIB at a population level. Available evidence shows that concurrent use of NSAIDs or aspirin with SSRIs greatly increases the risk of UGIB. The preventive strategy should be considered in those SSRI users at high risk, especially the elderly or those with a history of UGIB and taking nonselective NSAIDs or aspirin.