Gastrointestinal Risk Factors Research Articles

Efficacy of the Newest COX-2 Selective Inhibitors in Rheumatic Disease

Non-steroidal antiinflammatory drugs (NSAIDs) are standard treatment for the pain and inflammation associated with arthritis. Traditional NSAIDs and cyclooxygenase-2 (COX-2) selective inhibitors exhibit comparable efficacy, with different safety profiles. Traditional NSAIDs are associated with an increased risk of serious gastrointestinal (GI) adverse events versus COX-2 selective inhibitors, and chronic use frequently necessitates adjunctive therapy with gastroprotective agents. COX-2 selective inhibitors are often used in preference to avoid these GI adverse events. Recent studies have raised the concern that COX-2 selective inhibitors and traditional NSAIDs appear to be associated with a higher incidence of thrombotic cardiovascular events versus placebo. The key in prescribing these agents is for the physician to take a proactive approach to patient management and evaluation of GI and cardiovascular risk factors. This review examines the role of the newest COX-2 selective inhibitors, etoricoxib and lumiracoxib, in treating rheumatic disease.

Occurrence of human intestinal spirochetosis in comparison with infections by other enteropathogenic agents in an area of the Northern Italy

The aim of this study was to investigate the occurrence of human intestinal spirochetosis (IS) by a 16S rRNA restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) in a selected group (234) of patients with gastrointestinal complaints and/or potential risk factors for IS in comparison with the occurrence of infections by other enteropathogenic agents. By using 16S rRNA RFLP-PCR, 16 patients (6.8%) with IS were found (11 infected by Brachyspira aalborgi, 3 by Brachyspira pilosicoli, and 2 by both species); moreover, 10 patients with gastroenteric viruses (4.2%), 13 with enteropathogenic bacteria other than intestinal spirochetes (5.5%), and 24 with intestinal parasites (10.2%) were found. This study provides an enhancement of the knowledge about the distribution of IS, suggesting that it may be more frequent than suspected and that clinicians should consider IS when patients present with long-standing diarrhea. Moreover, 16S rRNA RFLP-PCR might be a powerful tool not only for diagnostic purpose but also to investigate the occurrence of IS just on fecal samples, not requiring invasive diagnostic techniques.

Gastrointestinal Symptoms After Infectious Diarrhea: A Five-Year Follow-Up in a Swedish Cohort of Adults

Gastrointestinal infection is a well-recognized trigger for functional bowel disorder. This study evaluated gastrointestinal symptoms and risk factors for their development after diarrheal disease of proven or strongly suspected infectious etiology in adults. The cohort of patients was derived from a previous study that determined the rate at which enteropathogens could be isolated at the time of diarrheal disease in adults. After 5 years, 717 of 851 patients were accessible for a questionnaire asking for persistence of gastrointestinal symptoms. Of 508 returned questionnaires, 333 were from patients with no previous gastrointestinal complaints. Forty-one (12%) of them had gastrointestinal symptoms for 3 months or more after the infectious diarrhea, and 31 (9%) still had symptoms at the end of the follow-up period. Irritable bowel syndrome was most common (68%), but other functional bowel disorder diagnoses were found in all but one of the others. Female gender (odds ratio, 2.65, 95% confidence interval, 1.28-5.50) and use of antibiotic treatment (odds ratio, 2.37; 95% confidence interval, 1.07-5.25) were risk factors for development of postinfectious functional bowel disorder. No increase in risk was associated with the type of enteropathogen causing diarrhea. Infectious diarrhea in previously healthy adults carried a substantial risk of triggering postinfectious functional bowel disorder. Irritable bowel syndrome was the most common, but other functional bowel disorders were also found. We did not find any new clinical tools that would facilitate the prediction of long-standing symptoms.

Use of gastroprotective agents in recommended doses in hospitalized patients receiving NSAIDs: a drug utilization study

In recent years, studies investigated to what extend recommendations for co-prescribing gastroprotective agents in prevention of NSAID-induced gastrointestinal complications are followed in clinical practice. However, only a few studies have also taken into consideration the recommended dose of gastroprotectives prescribed in NSAID-induced ulcer prophylaxis. The aim of our study was to evaluate the prevalence of concomitant use of gastroprotectives with NSAIDs in hospitalized patients, with emphasis on the recommended dose of gastroprotectives for ulcer prophylaxis. This observational, cross-sectional, drug utilization study included all adult patients receiving NSAIDs hospitalized in the Clinical Hospital Center Zagreb on the day of the study. Data on age, sex, comorbidities, indications for NSAID use, type/dose of NSAIDs and gastroprotectives, history of gastrointestinal events, active gastrointestinal symptoms and risk factors were evaluated. Study outcomes were: (1) prevalence of prescription of gastroprotectives among NSAID-users at risk; (2) prevalence of prescription of gastroprotective in recommended dose; (3) association between risk factors and prescription of GPAs. The rates of gastroprotectives prescription were significantly higher in NSAID-users with concomitant risk factors as compared to patients without risk factors [47/70 (67.1%) and 8/22 (36.4%), respectively; p=0.01072]. However, gastroprotection in recommended ulcer-preventive dose was low in both groups [8/70 (11.4%) and 9/92 (9.8%), respectively]. The number of concomitant risk factors did not increase the odds of receiving anti-ulcer therapy (odds ratio 0.7279). Thirty-three percent of patients with concomitant risk factors were not prescribed gastroprotectives. Ibuprofen, NSAID with the lowest risk of inducing gastrointestinal complications, was prescribed in only two patients. The results indicate high awareness among hospital physicians about possible NSAID-induced gastrointestinal complications, but insufficient knowledge about risk factors related to NSAID-induced gastrointestinal toxicity, recommended dose of gastroprotectives in NSAID-induced ulcer prophylaxis and gastrointestinal toxicity of different types of NSAIDs.

Nonsteroidal anti-inflammatory drugs (NSAIDs), cyxlooxygenase-2 selective inhibitors (coxibs) and gastrointestinal harm: review of clinical trials and clinical practice

BackgroundGastrointestinal harm, known to occur with NSAIDs, is thought to be lower with NSAID and gastroprotective agent, and with inhibitors selective to cyclooxygenase-2 (coxibs) at usual plasma concentrations. We examine competing strategies for available evidence of reduced gastrointestinal bleeding in clinical trials and combine this evidence with evidence from clinical practice on whether the strategies work in the real world, whether guidance on appropriate prescribing is followed, and whether patients adhere to the strategies.MethodsWe used a series of systematic literature searches to find full publications of relevant studies for evidence about the efficacy of these different gastroprotection strategies in clinical trials, and for evidence that they worked and were adhered to in clinical practice – whether they were effective. We chose to use good quality systematic reviews and meta-analyses when they were available.ResultsEvidence of efficacy of coxibs compared to NSAIDs for upper gastrointestinal bleeding was strong, with consistent reductions in events of about 50% in large randomised trials (34,460 patients), meta-analyses of randomised trials (52,474 patients), and large observational studies in clinical practice (3,093 bleeding events). Evidence on the efficacy of NSAID plus gastroprotection with acid suppressants (proton pump inhibitors, PPIs, and histamine antagonists, H2As) was based mainly on the surrogate measure of endoscopic ulcers. The limited information on damage to the bowel suggested that NSAID plus PPI was more damaging than coxibs.Eleven observational studies studied 1.6 million patients, of whom 911,000 were NSAID users, and showed that 76% (range 65% to 90%) of patients with at least one gastrointestinal risk factor received no prescription for gastroprotective agent with an NSAID. The exception was a cohort of US veterans with previous gastrointestinal bleeding, where 75% had gastroprotection with an NSAID. When gastroprotection was prescribed, it was often described as inadequate. A single study suggested that patient adherence to prescribed gastroprotection was low.ConclusionEvidence for efficacy of gastroprotection strategies with NSAIDs is limited. In clinical practice few patients who need gastroprotection get it, and those who get it may not take it. For coxibs, gastroprotection is inherent, although probably not complete.

Primer: managing NSAID-induced ulcer complications—balancing gastrointestinal and cardiovascular risks

Ulcer complications associated with the use of NSAIDs, in high-risk patients, are often caused by a failure to identify patients' risk factors, concomitant use of aspirin or multiple NSAIDs, and underutilization of gastroprotective agents. Current data suggest that cyclo-oxygenase 2 (COX2) inhibitors and some nonselective NSAIDs increase the risk of myocardial infarction. Physicians must, therefore, take into account both the gastrointestinal and the cardiovascular risks of individual patients when prescribing NSAIDs. In patients with a low cardiovascular risk, NSAIDs can be prescribed according to the level of gastrointestinal risk. Patients with a moderate gastrointestinal risk (one or two risk factors) should receive a COX2 inhibitor or an NSAID plus a PPI or misoprostol. Patients with more than two gastrointestinal risk factors or prior ulcer complications require the combination of a COX2 inhibitor and a PPI. Patients with a high cardiovascular risk (e.g. coronary heart disease or an estimated 10-year cardiovascular risk greater than 10%) should receive prophylactic aspirin and combination therapy with a PPI or misoprostol irrespective of the presence of gastrointestinal risk factors. Naproxen is the preferred NSAID because it is not associated with excess cardiovascular risk. Patients with a high cardiovascular risk and a very high gastrointestinal risk should avoid using NSAIDs or COX2 inhibitors.

Cardioprotective aspirin users and their excess risk of upper gastrointestinal complications

BackgroundTo balance the cardiovascular benefits from low-dose aspirin against the gastrointestinal harm caused, studies have considered the coronary heart disease risk for each individual but not their gastrointestinal risk profile. We characterized the gastrointestinal risk profile of low-dose aspirin users in real clinical practice, and estimated the excess risk of upper gastrointestinal complications attributable to aspirin among patients with different gastrointestinal risk profiles.MethodsTo characterize aspirin users in terms of major gastrointestinal risk factors (i.e., advanced age, male sex, prior ulcer history and use of non-steroidal anti-inflammatory drugs), we used The General Practice Research Database in the United Kingdom and the Base de Datos para la Investigación Farmacoepidemiológica en Atención Primaria in Spain. To estimate the baseline risk of upper gastrointestinal complications according to major gastrointestinal risk factors and the excess risk attributable to aspirin within levels of these factors, we used previously published meta-analyses on both absolute and relative risks of upper gastrointestinal complications.ResultsOver 60% of aspirin users are above 60 years of age, 4 to 6% have a recent history of peptic ulcers and over 13% use other non-steroidal anti-inflammatory drugs. The estimated average excess risk of upper gastrointestinal complications attributable to aspirin is around 5 extra cases per 1,000 aspirin users per year. However, the excess risk varies in parallel to the underlying gastrointestinal risk and might be above 10 extra cases per 1,000 person-years in over 10% of aspirin users.ConclusionIn addition to the cardiovascular risk, the underlying gastrointestinal risk factors have to be considered when balancing harms and benefits of aspirin use for an individual patient. The gastrointestinal harms may offset the cardiovascular benefits in certain groups of patients where the gastrointestinal risk is high and the cardiovascular risk is low.

Assessment of coxib utilization by rheumatologists for nonsteroidal antiinflammatory drug gastroprotection prior to the coxib market withdrawals

To examine cyclooxygenase 2 inhibitor (coxib) utilization by rheumatologists for patients receiving nonsteroidal antiinflammatory drugs (NSAIDs) prior to the coxib market withdrawals. A prospective study of patients with rheumatoid arthritis enrolled in the Consortium of Rheumatology Researchers of North America registry was performed. Of 1,833 patients receiving prescription NSAIDs, 1,380 (75.3%) received gastroprotection, defined as either coxib monotherapy and/or gastroprotective agent (GPA) cotherapy, and 1,207 (65.8%) received coxibs. The distribution of gastroprotective strategies included 860 (46.9%) patients who were prescribed coxib monotherapy, 347 (18.9%) prescribed dual coxib plus GPA cotherapy, 173 (9.4%) prescribed a nonselective NSAID (NS-NSAID) plus GPA cotherapy, and 453 (24.7%) prescribed an NS-NSAID without GPA cotherapy. For patients with 0, 1, and > or =2 identifiable gastrointestinal (GI) risk factors, coxib prescribing rates as a proportion of NSAID agents were 64.1%, 66.4%, and 68.6%, respectively; among dual aspirin/NSAID users, coxib prescribing rates were 66.2%, 78.3%, and 68.5% of NSAID prescriptions, respectively. The majority of NSAID users were prescribed a gastroprotective strategy, primarily attributable to coxib utilization. Coxib utilization rates were consistently high across all levels of GI risk, including patients without identifiable risk factors. These data indicate that rheumatologists broadly adopted the coxib class of NSAIDs in a nonselective manner with respect to underlying GI risk and concomitant aspirin use. As novel therapeutic classes are introduced, early evaluation of prescribing patterns using arthritis registries can determine the appropriateness of prescribing patterns and may improve patient outcomes.

Channeling and prevalence of cardiovascular contraindications in users of cyclooxygenase 2 selective nonsteroidal antiinflammatory drugs

To assess use and channeling of cyclooxygenase 2 selective inhibitors (coxibs) over time and to estimate the percentage of coxib users with cardiovascular contraindications. The study population comprised all coxib and nonselective nonsteroidal antiinflammatory drug (NSAID) users in the Integrated Primary Care Information project between January 2000 and December 2004. The prevalence of risk factors for NSAID-related upper gastrointestinal ulcer complications, cardiovascular disease, and cerebrovascular disease at the start of treatment was compared between users of coxibs and users of nonselective NSAIDs. The study population included 72,841 nonselective NSAID users and 10,739 coxib users. The prevalence of risk factors for NSAID-related gastrointestinal complications was higher in coxib users than nonselective NSAID users (odds ratio [OR] 1.18, 95% confidence interval [95% CI] 1.10-1.26). Similarly, the prevalence of prior cardiovascular disease was higher in coxib users than in nonselective NSAID users (OR 1.35, 95% CI 1.28-1.43). Channeling of coxibs to patients with NSAID-related gastrointestinal risk factors declined after 2001 but increased again in 2004, whereas the channeling of coxibs to patients with cardiovascular disease remained constant. Less than 15% of all coxib users had history of ischemic coronary or cerebrovascular disease. Among coxib users with increased risk for NSAID-related gastrointestinal disorders, 27% had history of ischemic coronary or cerebrovascular disease. This study demonstrates that coxibs were preferentially prescribed to patients with risk factors for NSAID-related gastrointestinal disorders and/or cardiovascular diseases. Only one-quarter of coxib users with increased risk for NSAID-related gastrointestinal complications had cardiovascular conditions compatible with recent European safety contraindications for coxibs.

Instrumental Variable Analysis of Secondary Pharmacoepidemiologic Data

Instrumental Variable Analysis of Secondary Pharmacoepidemiologic Data

GI Risk and Risk Factors of NSAIDs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used drugs in the United States. Ulcers are found at endoscopy in 15% to 30% of patients using NSAIDs regularly. The annual incidence of upper gastrointestinal (GI) complications such as bleeding with regular NSAID use is approximately 1.0% to 1.5%, whereas the annual rate of upper GI clinical events (complicated plus symptomatic uncomplicated ulcers) is approximately 2.5% to 4.5%. Upper GI symptoms such as dyspepsia also occur in many patients taking NSAIDs--at a relative risk of about 1.5 to 2 compared with that in patients without NSAID use. Important risk factors for upper GI clinical events include older age, prior history of upper GI events, use of corticosteroids or anticoagulants, and high-dose or multiple NSAIDs (including NSAID plus low-dose aspirin). Lower GI clinical events such as bleeding may also occur with NSAIDs, although they are less common and less well studied than upper GI events. The decision to employ a protective strategy to decrease NSAID-associated GI clinical events is based on risk stratification. Strategies employed include the use of non-NSAID analgesics, use of lowest effective dose of NSAID, use of medical cotherapy (eg, proton pump inhibitor, misoprostol), or use of coxibs.

Prevention and treatment of NSAID-induced gastroduodenal injury

NSAIDs increase the risk of gastrointestinal (GI) complications. Those at risk should be considered for alternatives to NSAID therapy, modifications of risk factors, and prevention strategies with co-therapy with gastroprotective agents (proton-pump inhibitors or misoprostol) or COX-2 selective inhibitors (coxibs). Since coxibs, and probably other nonselective NSAIDs, may increase the risk of cardiovascular events, prevention strategies must take into account both GI and cardiovascular risk factors. All NSAIDs and coxibs should be prescribed at the lowest possible dose and for the shortest period of time. In patients with GI risk factors but no cardiovascular risk, coxibs or NSAIDs plus PPI or misoprostol are valid options. Patients with a history of ulcer bleeding should receive coxib plus PPI therapy and should be tested and treated for Helicobacter pylori infection. Most patients with increased cardiovascular risk will be treated with antiplatelet agents. It is not known whether co-therapy with low-dose aspirin will reduce the incidence of cardiovascular events, but it will further increase GI risk. It is currently unclear whether the risk of developing upper GI events with coxib plus aspirin is lower than it is with NSAIDs plus aspirin. However, all these patients should benefit from PPI co-therapy. Helicobacter pylori eradication should be considered as an additional therapeutic option when we want to further reduce the GI risk in specific patients. When the lower GI tract is of concern, coxib rather than NSAID therapy should be considered as the first option. Coxib therapy has better GI tolerance than NSAIDs, but patients with peptic ulcers or dyspepsia during NSAID/coxib treatment need PPI co-therapy.

The prevalence of risk factors for gastrointestinal complications and use of gastroprotection among persons hospitalized for cardiovascular disease

Aspirin is often used in patients with cardiovascular disease, but it can also cause gastrointestinal complications. Proton pump inhibitors reduce the risk of gastrointestinal complications in aspirin users with a history of gastrointestinal complications. To determine the prevalence of gastrointestinal risk factors in aspirin users and the prevalence of proton pump inhibitor utilization in high-risk patients. We reviewed all patients admitted to hospital between April and October 2004 with a diagnosis of cardiovascular disease. We collected data on demographics, medication use, comorbid illnesses, previous gastrointestinal complications, and medication use on admission and discharge. A total of 324 patients were admitted with cardiovascular disease of whom 94% were discharged on aspirin. Seventy-eight per cent of patients admitted had at least one gastrointestinal risk factor in addition to having cardiovascular disease, and 15% had three or more additional gastrointestinal risk factors. Patients with additional gastrointestinal risk factors were more likely to be prescribed proton pump inhibitor therapy (27% vs. 10%, P < 0.001). Only 10% of proton pump inhibitor-naíve high-risk aspirin users were prescribed a proton pump inhibitor upon discharge. The majority of high-risk aspirin users are not receiving proton pump inhibitors for gastroprotection. Further work is required to encourage providers to consider the use of gastroprotective strategies in appropriate patients.

Retrospective analysis of utilization patterns and cost implications of coxibs among seniors in Quebec, Canada: What is the potential impact of the withdrawal of rofecoxib?

In September 2004, the manufacturer of rofecoxib announced a voluntary worldwide withdrawal of the drug. The impact of this withdrawal on drug budgets is unclear. This study evaluated average daily doses and costs of rofecoxib and celecoxib and concomitant use of gastroprotective agents (GPAs) in elderly patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in Quebec, prior to the rofecoxib withdrawal. This retrospective cohort study used prescription drug and medical service data from the Quebec government health agency administrative database and included coxib users > or =66 years of age with OA or RA who filled > or =3 consecutive rofecoxib or celecoxib prescriptions in 2001-2002. Results were adjusted for gastrointestinal risk factors and other patient baseline characteristics. Data were analyzed for 11,975 rofecoxib and 12,480 celecoxib users. Mean daily dosages were 20.7 mg for rofecoxib and 231.3 mg for celecoxib. Rofecoxib users consumed a mean +/- SD of 0.95 +/- 0.43 pills per day, and celecoxib users took 1.34 +/- 0.65 pills per day. Mean +/- SD unadjusted daily acquisition costs were $1.18 +/- $0.53 (Canadian) for rofecoxib and $1.45 +/- $0.74 for celecoxib. After adjusting for patient baseline characteristics, the mean daily acquisition cost for rofecoxib was $0.25 lower than for celecoxib. Rofecoxib users were less likely than celecoxib users to fill a GPA coprescription (odds ratio 0.88; 95% confidence interval 0.81, 0.95). Subgroup analyses yielded comparable results. Celecoxib appears to be a more expensive therapeutic option than rofecoxib due to a relatively higher daily dose and tablet consumption.

Management of High-risk Patients on Non-steroidal Anti-inflammatory Drugs or Aspirin

Low-dose aspirin is increasingly used for the primary prevention of cardiovascular events. However, current evidence suggests that the gastrointestinal and other bleeding risks of aspirin probably outweigh its potential benefits in primary prevention. Various strategies have been proposed to reduce the gastrointestinal risk of aspirin, including gastroprotection with a proton pump inhibitor (PPI), eradication of Helicobacter pylori infection and replacing aspirin with other anti-platelet agents. Although co-therapy with a PPI and the eradication of H. pylori substantially reduce the risk of recurrent ulcer bleeding with aspirin, the replacement of aspirin by clopidogrel cannot be recommended to patients with a high gastrointestinal risk. Traditionally, strategies for the prevention of non-steroidal anti-inflammatory drug (NSAID)-induced ulcer complications included co-therapy with a gastroprotective agent and the substitution of cyclooxygenase (COX)-2 inhibitors for non-selective NSAID. Evidence emerged recently that COX-2 inhibitors and some non-selective NSAID increase cardiovascular risk. Before prescribing anti-inflammatory therapy, both gastrointestinal and cardiovascular risk factors of individual patients need to be evaluated. In patients with increased cardiovascular risk requiring anti-inflammatory analgesics, the combination of a non-selective NSAID, low-dose aspirin and a PPI is the preferred treatment.

Systematic review: coxibs, non‐steroidal anti‐inflammatory drugs or no cyclooxygenase inhibitors in gastroenterological high‐risk patients?

Selective cyclooxygenase-2 inhibitors have been marketed as alternatives of conventional, non-steroidal anti-inflammatory drugs with the purpose of reducing/eliminating the risk of ulcer complications. Unexpectedly, randomized-controlled trials revealed that long-term use of coxibs, such as rofecoxib, significantly increased the risk of myocardial infarction and stroke, while the use of valdecoxib was associated with potentially life-threatening skin reactions. Subsequently, rofecoxib and valdecoxib were withdrawn from the market. Although more strict precautions for other coxibs, such as celecoxib, etoricoxib, lumiracoxib and parecoxib, may be accepted/recommended by regulatory agencies, a critical review of published data suggests that their use may not be justified - even in high-risk patients - taking benefits, costs and risks into consideration. Clinicians should, therefore, never prescribe coxibs to patients with cardiovascular risk factors, and should only reluctantly prescribe coxibs to patients with a history of ulcer disease or dyspepsia to overcome persistent pain due to, e.g. rheumatoid arthritis or osteoarthritis. Instead, they should consider using conventional non-steroidal anti-inflammatory drugs in combination with a proton pump inhibitor or a prostaglandin analogue, especially for patients with increased cardiovascular risks, i.e. established ischaemic heart disease, cerebrovascular disease and/or peripheral arterial disease, or alternatively acetaminophen. An evidence-based algorithm for treatment of a chronic arthritis patient with one or more gastrointestinal risk factors is presented.

Utilization Patterns of Gastroprotective Agents among NSAID Treated Subjects with Varying Gastrointestinal and Cardiovascular Risk Profiles in a Health Benefits Population

Purpose: The purpose of this study was to gain an understanding of the patterns of Gastroprotective Agent (GPA) utilization among users of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) with varying Gastrointestinal (GI) and Cardiovascular (CV) risk profiles. Methods: A cross-sectional analysis was completed using the claims of a large health benefits company. A total of 24-months of claims data were analyzed for all eligible subjects. Subjects included those 18 years of age and older, with a prescription claim (i.e. the index claim) for an NSAID between 1 April 2003 and 30 June 2003, who maintained continuous plan enrollment during the study period. Subjects were also required to maintain chronic NSAID utilization, defined as at least 90 days supply of the index medication during the 12-month post-index period. Study subjects were stratified into the following three cohorts based upon their index medication: (1) Cox-II selective inhibitors, (2) non-selective NSAIDs (excluding naproxen), and (3) naproxen. Subjects were further stratified based upon the presence or absence of concomitant GPA utilization during the 12-month post-index period. Finally, subjects were assessed for the presence or absence of risk factors associated with CV and/or GI events during the 12-month pre-index period. Results: The study population consisted of 27,827 subjects, with a mean age of 61.4 (± 13.5) years. Of the population, 13,408 subjects (48.2%) were treated with non-selective NSAIDs, 5397 (19.4%) with naproxen, and 9022 (32.4%) with Cox-II inhibitors. The proportion of GPA utilization was significantly different (P < 0.0001) among the non-selective NSAID, naproxen, and Cox-II cohorts, with 22.2%, 19.2%, and 29.2%, respectively. Additionally, the proportion of subjects with at least one risk factor for a GI event was significantly different (P < 0.0001) among the cohorts, with 84.6% of non-selective NSAIDs, 84.4% of naproxen, and 48.2% of Cox-IIs. Finally, no significant difference (P = 0.1842) was found in the proportion of subjects with CV risk factors among study cohorts. Conclusions: The distribution of subjects with at least one GI risk factor was found to be significantly higher in the non-selective NSAID and naproxen cohorts; however, GPA utilization was significantly lower in these cohorts when compared to users of Cox-II inhibitors.

Review article: low-dose aspirin, non-steroidal anti-inflammatory drugs and cyclo-oxygenase inhibitors - balancing risks and benefits

Summary In recent years, there has been a rapid increase in the number of patients using aspirin for the prevention of cardiovascular events and also other non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, for the treatment of arthritis. However, aspirin and non-steroidal anti-inflammatory drugs are associated with an increase in gastrointestinal risk. Recent studies have shown that cyclo-oxygenase-2 inhibitors, and possibly non-selective non-steroidal anti-inflammatory drugs, increase the cardiovascular risk. In patients taking aspirin, the ‘gold standard’ therapy to reduce gastrointestinal risk is concomitant therapy with a gastroprotective agent, such as a proton-pump inhibitor. Other gastroprotective agents, such as misoprostol, while equally effective may be associated with a higher proportion of adverse events. Helicobacter pylori infection has been shown to increase the risk of upper gastrointestinal bleeding associated with low-dose aspirin. Emerging data suggest that the eradication of H. pylori reduces the gastrointestinal risk of high-risk aspirin users. Other antiplatelet agents such as clopidogrel that were thought to be non-ulcerogenic have been widely used as alternatives to aspirin. However, recent studies have shown that clopidogrel induces an unacceptably high rate of ulcer bleeding in high-risk patients. When prescribing non-steroidal anti-inflammatory drugs therapy, treatment needs to be individualized according to the patients’ gastrointestinal and cardiovascular risk factors.

ASPIRIN USE IN PATIENTS TAKING SELECTIVE COX-2 INHIBITORS OR NON-SELECTIVE NSAID THERAPY IN A MANAGED CARE SETTING

Purpose: Guidelines suggest aspirin use for patients with a history of cardiovascular disease (CHD) or diabetes mellitus (DM). Aspirin taken with selective (COX-2) and non-selective NSAIDs may lead to increased risk of gastrointestinal (GI) adverse events. This study measured aspirin use and evaluated its association with GI risk factors and gastroprotective medication use in patients with CHD or DM who were chronically using COX-2 or NSAID therapy. Methods: This analysis employed a survey of patients identified from administrative claims data from two large managed care plans in the Southeastern and Western US. The study included patients with prior diagnosis of CHD or DM who were chronic users of NSAID/COX-2 (minimum of two prescriptions during most recent 6 months) and continuously eligible in the health plan from 2/1/2002 to 1/31/2004. Trained interviewers obtained the patient reported information including use of aspirin and over the counter medications during a telephone survey. Patient characteristics between aspirin users and non-users were compared using bivariate statistics. Results: In all, 1,067 patients (response rate: 20%) were surveyed. Of the survey respondents, 48% took aspirin. Among aspirin users, 61% took a gastroprotective medication, with 41% taking a proton pump inhibitor. Additionally, 92% of patients had at least one GI risk factor. Differences in GI risk factors across patients with and without aspirin are given in the table below. Aspirin users were more likely to be older than 65 years [OR:1.28; CI:1.00 – 1.64], more likely to be smokers [OR:1.36; CI:1.06 – 1.75], and more likely to be males [OR:1.71; CI:1.33 – 2.21]. However, gastroprotective medication use was equal across aspirin users and non-users [OR: 1.10; CI 0.85–1.41].TableConclusions: In the surveyed patient population, less than 50% of patients with CHD or DM reported aspirin use. Additionally, in patients using aspirin and NSAID/COX-2s with GI risk factors, appropriate use of gastroprotective medications may be sub-optimal.

Use of gastrointestinal preventive therapy among elderly persons receiving antiarthritic agents in Nova Scotia, Canada

Background: Two different strategies, referred to as gastrointestinal (GI) preventive therapy (GIPT), have been recommended for high-risk patients to prevent GI complications associated with antiarthritic therapy with nonsteroidal anti-inflammatory drugs (NSAIDs): (1) use of a gastroprotective agent (GPA) along with the NSAID or (2) use of a cyclooxygenase-2-selective inhibitor (COX-2SI). The COX-2SIs rofecoxib and celecoxib have been shown to be as effective as traditional NSAADs for pain relief, but with an improved GI safety profile. Objective: The purpose of this study was to examine the utilization of GIPT by elderly persons in Nova Scotia who were taking antiarthritic medications and to identify the factors associated with their use of GIPT. Methods: A retrospective, cross-sectional study was conducted using administrative data from the Nova Scotia Seniors' Pharmacare Program database. Study participants were aged ≥65 years and had filled a prescription for a COX-2SI, a traditional NSAID, or high-dose aspirin at some point between January 1, 2001 and August 31, 2002. Subjects with at least 1 risk factor (as defined by our study) who received GIPT were classified as receiving appropriate therapy. Subjects with risk factors who did not receive GIPT were classified as potential underutilizers of GIPT. Subjects without risk factors who received GIPT were classified as potential overutilizers of GIPT. Descriptive statistics were presented, and factors independently associated with receiving GIPT were assessed using logistic regression. Results: The study included 14,587 seniors: 3647 used COX-2SIs, 9412 used traditional NSAIDs alone, and 1528 used traditional NSAADs plus a GPA. Subjects were predominantly female (age range, 65–74 years). In subjects with at least 1 risk factor, 63% were classified as potential underutilizers of GIPT. Thirty-three percent of subjects with no risk factors were classified as potential overutilizers of GIPT. Factors significantly associated with receiving a GIPT included Female gender, annual income >$50,000, urban residence, age ≥75 years, GI complication in the previous year, and concomitant use of warfarin or corticosteroids. Conclusion: Potential under utilization of GIPT in this subject population was more prevalent than potential overutilization of GIPT. Although all hypothesized risk factors were significantly associated with receiving GIPT, physician education on GI risk factors might improve prescribing of GIPT for elderly persons in Nova Scotia.