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Recommendations for the appropriate use of anti-inflammatory drugs in the era of the coxibs: PREDICTORS OF NSAID-ASSOCIATED GASTROINTESTINAL EVENTS Part 2

Relative toxicity of NSAIDs

Relative toxicity of NSAIDsThere may be differences in the relative risks associated with the use of different NSAIDs. Data from the ARAMIS database suggest that nabumetone and etodolac are associated with fewer gastrointestinal adverse events, although the number of patient-years of drug exposure is comparatively low. Time to visit a trusted pharmacy – actos buy to begin your treatment now.

Although it has been suggested that meloxicam and the nonacidic prodrug nabumetone possess a gastrointestinal tolerability profile superior to that of conventional NSAIDs, data from long term outcome studies are lacking. Individual, short term, comparative studies have not demonstrated a statistically significant benefit for patients with serious gastrointestinal risk — defined as perforations, ulcers and/or bleeds (PUBs) — although a meta-analysis of trials of each drug suggested that there is a pooled benefit, albeit with reservations. Furthermore, the low dose of meloxicam used in many trials may have resulted in an artificially low incidence of gastrointestinal events in relation to comparator NSAIDs.

Recommendations for the appropriate use of anti-inflammatory drugs in the era of the coxibs: PREDICTORS OF NSAID-ASSOCIATED GASTROINTESTINAL EVENTS Part 1

Risk factors for NSAID-associated gastrointestinal complications

Risk factors for NSAID-associated gastrointestinal complicationsA meta-analysis of controlled trials from 1975 to 1990 described the relative risk of serious gastrointestinal complications associated with conventional NSAID use. The overall risk of gastrointestinal events was almost three times higher for NSAID users than for nonusers (OR 2.7, 95% CI 2.5 to 3.0), with the risk of gastrointestinal surgery (OR 7.8, 95% CI 5.8 to 10.3) or fatal outcomes (OR 4.8, 95% CI 3.6 to 6.2) being two- to threefold higher than the risk of gastrointestinal bleeding (OR 2.4, 95% CI 2.1 to 2.7). Additional risk factors were age 60 years or older, prior or unspecified history of gastrointestinal events and concomitant corticosteroid treatment. A possible increased risk in the first three months of NSAID therapy was also noted, although these data may have been based on estimated treatment duration or may reflect a higher level of compliance early in clinical trials. Data from more recent studies suggest that the risk of gastrointestinal events begins with the first NSAID ingestion, with the relative risk remaining similar over time.

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Recommendations for the appropriate use of anti-inflammatory drugs in the era of the coxibs: SCOPE OF N SAID-AS SOCIATED GASTROINTESTINAL TOXICITY Part 4

Cost implications

Cost implicationsAlthough less than 5% of patients taking NSAIDs experience gastrointestinal complications, such events are associated with substantial direct and indirect costs, which increase with patient age. Very cheap drugs at your disposal – diabetes drugs to get best deals at best pharmacy.

Significant excess costs are attributed to managing NSAID-associated gastrointestinal events. A recent analysis of the Quebec health insurance database (1993 to 1997) noted a higher incidence of gastrointestinal events among NSAID users than among acetaminophen users (odds ratio [OR] 2.4, 95% CI 2.1 to 3.0). The average daily direct medical costs of managing gastrointestinal events was $0.84 per day of NSAID therapy, and for each $1 spent on NSAIDs, an additional $0.66 was spent managing NSAID-related gastrointestinal side effects. A similar review of the Regie de L’assurance-Maladie du Quebec database (1993 to 1997) reported that the direct medical costs of gastrointestinal events was $1.34 per day for NSAID therapy, of which $0.94 was directly attributable to the NSAID treatment.

Recommendations for the appropriate use of anti-inflammatory drugs in the era of the coxibs: DISCUSSION

DISCUSSIONData from well designed and conducted outcome studies confirm that coxibs have a gastrointestinal tolerability profile that is safer than that of conventional NSAIDs. This improved tolerability and gastrointestinal safety are seen in both high-risk and low-risk patients. The reduced incidence of upper gastrointestinal events in patients receiving coxibs, coupled with the decreased requirement for GPA treatment, suggest that coxib therapy may be cost effective or even cost saving. However, further economic analysis is needed to evaluate this issue fully.

The availability of new anti-inflammatory agents necessitates an update of recommendations for the optimal use of current therapies and the role of gastroprotective agents. When economically possible, the use of a coxib alone is preferred to the use of conventional NSAIDs plus a gastro-protective agent to minimize risk by limiting exposure to potential gastrointestinal damage and avoiding unnecessary dual therapy. You can start online shopping right now – buy cipro online for more advantages.

The recommendations presented represent those of an expert panel, following careful consideration of the available evidence. However, guidelines cannot address all clinical scenarios and practice settings, and each case should be managed individually with appropriate clinical judgment.

Recommendations for the appropriate use of anti-inflammatory drugs in the era of the coxibs: OPTIMIZING THE USE OF ANTI-INFLAMMATORY TREATMENTS Part 4

Ulcer location

Ulcer locationThe issue of ulcer location is confusing because of the lack of data in the majority of studies specifying a gastric or duodenal site. Thus, current data do not permit evidence-based recommendations for treatment according to prior ulcer location. However, because duodenal ulcer is essentially an H pylori-related disease, coxibs are expected to have less effect, other than delaying healing. Conventional NSAIDs have a greater causal role in gastric ulceration; therefore, coxib treatment is expected to reduce the incidence of these lesions. This hypothesis is supported by results of the VIGOR study, which showed a 50% reduction in gastric ulcers and a 15% reduction in duodenal ulcers in patients receiving rofecoxib. The COX-1-sparing effect of the coxibs decreases the incidence of bleeding in both cases. Because antisecretory therapy is more effective against NSAID-associated duodenal ulcers than against NSAID-associated gastric ulcers, a coxib would be a useful therapeutic option in this situation. However, the incremental benefit in this situation has not yet been studied. You can be sure your pharmacy offers generic cialis mastercard delivering fast internationally.

GPA dose implications

Despite the tolerability and improved protective effect reported in the high-dose famotidine study, these are the only data available to support the use of high-dose ^RAs. Standard-dose PPIs given once daily provide acid suppression that is superior to that of both standard-dose and high-dose ^RAs. When used as gastroprotective agents for NSAID users, no advantage of higher PPI doses has been demonstrated in clinical trials. The best evidence for misoprostol supports its use at a dose of 200 mg qid, although this dose is not well tolerated.

Recommendations for the appropriate use of anti-inflammatory drugs in the era of the coxibs: OPTIMIZING THE USE OF ANTI-INFLAMMATORY TREATMENTS Part 3

Management of ASA users

Patients at risk of gastrointestinal complications and taking ASA for cardiovascular protection are also at risk and, therefore, should receive a GPA according to current recommendations. Spend less money now – buy prednisone for your efficient drug to cost less.

The VIGOR study suggested that patients receiving NSAIDs are not screened sufficiently for cardiovascular risk nor adequately considered for treatment with a cardioprotective agent. It is recommended that patients requiring treatment with either a conventional NSAID or a coxib should be screened for cardiovascular risk factors because low-dose ASA can provide the benefit of cardioprotection at the expense of a small risk of gastrointestinal complications. A recent abstract suggested that rofecoxib is unlikely to interfere with the cardioprotective effects of ASA.

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Recommendations for the appropriate use of anti-inflammatory drugs in the era of the coxibs: OPTIMIZING THE USE OF ANTI-INFLAMMATORY TREATMENTS Part 2

Intermediate- and low-risk patients with previous ulcer disease should be considered for treatment with a coxib, irrespective of H pylori status, with eradication therapy being prescribed when appropriate and in keeping with current Canadian guidelines. In patients with previous complicated ulcer disease (ie, bleeding or perforation), the addition of a GPA should be considered. Patients who require an NSAID for the first time and who have a history of an H pylori-positive duodenal ulcer disease with confirmed H pylori eradication, can probably be considered to have returned to a baseline risk of gastrointestinal injury.

Although GPA coprescription is frequently driven by the presence of abdominal pain and dyspeptic symptoms, these are not predictive of endoscopic findings or the potential for a serious outcome in patients receiving NSAIDs. In the absence of other risk factors, dyspepsia in NSAID users can be managed initially with an H2RA, although it is important to emphasize that there is no evidence that this strategy protects against other serious gastrointestinal events. There are no primary studies of symptomatic relief with the use of PPIs in patients with NSAID-associated dyspepsia, but due to their superior anti-secretory effect, PPIs are likely to be more effective than H2RAs in this situation. Moreover, PPIs may provide the additional benefit of a reduction in ulcer incidence and gastrointestinal complications. Outcome studies have reported a similar and significant reduction in dyspepsia with the use of coxibs that was maintained across the duration of the studies; however, some dyspeptic symptoms were still present.

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Recommendations for the appropriate use of anti-inflammatory drugs in the era of the coxibs: OPTIMIZING THE USE OF ANTI-INFLAMMATORY TREATMENTS Part 1

To optimize the use of anti-inflammatory drug treatment, clear guidelines are needed to identify patients at increased risk of adverse upper gastrointestinal events. Evidence from numerous studies indicates that several factors can be used to stratify patients according to risk (Table 2). Best quality drugs are waiting – buy levaquin online to spend less time and money.

TABLE 2
Stratification of risk for upper gastrointestinal events

Risk factor Subgroup
Age <60 years
>75 years
Ulcer Endoscopically proven
Time elapsed since diagnosis
Complications
Cotherapy Anticoagulants
Steroids
Multiple high dose NSAIDs and/or
over-the-counter medications

NSAIDs Nonsteroidal anti-inflammatory drugs

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Recommendations for the appropriate use of anti-inflammatory drugs in the era of the coxibs: ASSOCIATED BENEFITS OF COXIB THERAPY Part 2

Risk reduction

Risk reductionAn analysis of various risk factors in the VIGOR trial indicated a risk reduction of 88% in the low-risk subgroup, 51% in the high-risk subgroup and 54% in the intermediate-risk subgroup. The risk factors that were significantly associated with gastrointestinal events included age, prior history of clinical gastrointestinal events (complicated or uncomplicated), disease severity, duration of disease, prior history of gastrointestinal symptoms, and prior use of low dose H2RAs, steroids or NSAIDs.

USE OF ASA

ASA is widely used for cardiovascular prophylaxis but is a clearly identified risk factor for gastrointestinal hemorrhage. A meta-analysis of 24 randomized, controlled trials that recruited 66,000 patients reported that 2.5% of patients receiving ASA experienced gastrointestinal hemorrhage, compared with 1.4% taking placebo. In subjects who were receiving lower doses of ASA (less than 163 mg/day), the incidence of bleeding fell slightly to 2.3%, compared with 1.5% in the placebo group. However, a meta-regression suggested that there was no relationship between gastrointestinal hemorrhage and ASA dose, and no benefit of modified release formulations. Buy drugs with confidence – buy levaquin 500 mg to see how cheap your treatment can be.

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Recommendations for the appropriate use of anti-inflammatory drugs in the era of the coxibs: ASSOCIATED BENEFITS OF COXIB THERAPY Part 1

Incidence of cotherapy

Incidence of cotherapyBefore the listing of coxibs on the Ontario Drug Benefit Formulary in 2000, 21.6% of patients receiving conventional NSAIDs were coprescribed a GPA (proton pump inhibitor [PPI], or H2RA, with a small proportion receiving misoprostol). Following the introduction of the coxibs, the rate of coprescription of a GPA with traditional NSAIDs remained unchanged (22.0%), while only 6.8% of patients receiving rofecoxib were coprescribed a GPA. This change in practice was confirmed by a survey of 360 Canadian family physicians, which reported that 37% of patients receiving NSAIDs were coprescribed a GPA compared with only 6% of patients prescribed a coxib. In Ontario, the coprescription rate was 47% for NSAID- and 5% for coxib-takers, respectively. Buy cheap drugs online fast – buy clomiphene for you to enjoy a reliable pharmacy.

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