High Gastrointestinal Risk Research Articles

NSAID PRESCRIPTION SURVEY IN INTEGRATED TRADITIONAL AND WESTERN MEDICINE TREATMENT: ASSESSING GASTROINTESTINAL AND CARDIOVASCULAR RISKS

Introduction: Non-steroidal anti-inflammatory drug (NSAID) usage should be carefully considered based on gastrointestinal (GI) and cardiovascular (CV) risks. In light of restricted evidence, this study aims to assess the prescription of NSAIDs concerning the GI and CV risks in the integrated treatment of Traditional medicine (TM) and Western medicine (WM). Materials and method: A retrospective cross-sectional study was conducted on 393 medical records of inpatients using NSAIDs in 2022 at the Traditional Medicine Hospital of Ho Chi Minh City. GI and CV risks, as well as information regarding NSAID prescriptions, were recorded. A multivariable regression model was employed to identify factors associated with the prescription of NSAID groups. Results: NSAIDs were primarily prescribed for musculoskeletal and connective tissue disorders (87.28%). Approximately half of the cases exhibited moderate to high GI risk (47.59%), while for CV risk, there were 68.95% with moderate to very high risk. COX-2 inhibitors were the most commonly prescribed (94.66%), even when considering GI and CV risks separately. In the majority, NSAID prescriptions aligned with both risks according to American College of Gastroenterology (ACG) guidelines (73.79%). The prescription of NSAID groups was significantly influenced by patient gender, ailment type, and physician education (p<0.05), but not by GI and CV risks (p>0.05). Conclusion: Patients receiving NSAIDs in integrated TM and WM treatment often faced an increased GI and CV risk, with the majority adhering to ACG guidelines. However, GI and CV risks were not significantly considered for NSAID group selections. Multi-center studies should be conducted.

Non-steroidal anti-inflammatory drugs (NSAIDs), pain and aging: Adjusting prescription to patient features.

A narrative review of papers published from January 2011 to December 2021, after a literature search in selected databases using the terms "pharmacokinetics", "ibuprofen", "diclofenac", "acemetacin", "naproxen", "etodolac" and "etoricoxib" was performed. From 828 articles identified, only eight met the inclusion criteria. Selective COX-2 inhibitors are associated with higher cardiovascular risk, while non-selective COX inhibitors are associated with higher gastrointestinal risk. NSAIDs with lower renal excretion with phase 2 metabolism are less likely to induce adverse effects and drug-drug interactions. Patients with frequent NSAID use needs, such as elderly patients and patients with cardiovascular disease or impaired renal function, will benefit from lower renal excretion (e.g. acemethacin, diclofenac, and etodolac) (level of evidence 3). Polymedicated patients, elderly patients, and patients with chronic alcohol abuse will be at a lower risk for adverse effects with NSAIDs that undergo phase 2 liver biotransformation, namely, acemethacin and diclofenac (level of evidence 3). Young patients, patients dealing with acute pain, or with active and/or chronic symptomatic gastritis, selective COX-2 inhibitors (celecoxib or etoricoxib) may be a better option (level of evidence 2). Knowing the individual characteristics of the patients, combined with knowledge on basic pharmacology, offers greater safety and better adherence to therapy. PERSPECTIVE: Although there are several NSAIDs options to treat pain, physicians usually take special care to its prescription regarding cardiovascular and gastrointestinal side effects, despite the age of the patient. In this paper, based on the best evidence, the authors present a review of the safest NSAIDs to use in the elderly.

Non-steroidal anti-inflammatory drugs in the elderly. Agreement with safe prescription recommendations according to cardiovascular and gastrointestinal risks

Introduction/objectiveNon-Steroidal Anti-Inflammatory Drugs are the cornerstone in the treatment of acute and chronic pain due to inflammation in musculoskeletal conditions. Even though adverse side-effects are associated, their use is common in the elderly patients. Our aim is to determine the prescription trend of NSAIDs, the evaluation for gastrointestinal (GI) and cardiovascular (CV) risks, and the level of agreement with prescription guidelines. MethodsWe conducted an observation and descriptive study in a general hospital geriatrics consultation. ResultsFrom the 231 patients only 59 patients had a NSAIDs prescription. The most frequently prescribed was Acetaminophen, in 29(49.1%) patients, Celecoxib was prescribed in 11(18.6%) patients, Piroxicam in 5(8.4%) patients, Acetaminophen plus Celecoxib plus Omeprazole in 4 (6.7%), Acetaminophen plus Piroxicam in 2 (0.3%) patients, and Acetaminophen plus Diclofenac plus Celecoxib in 1 patient (1.6%). In the Framingham risk classification there were 160/231 (69.3%) patients in Very High Risk and 71/231 (30.7%) patients in High Risk. There were no patients in Low Risk. GI Risk: 79 patients (34.1%) had a peptic ulcer disease history. There were 55/231 (23.8%) in the High GI Risk classification, 102/231 (44.1%) in Intermediate GI Risk and 74/231 (32%) in the Low Risk. The level of agreement between the prescribed versus recommended NSAIDs according the CV and GI risks was measured with a contingence table and the kappa statistic of 0.37 p=0.001. ConclusionThere is a low level of agreement between prescribed and recommended NSAID in elderly population.

Practice Advisory on the Appropriate Use of NSAIDs in Primary Care.

Cyclo-oxygenase (COX)-2 selective and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are important in managing acute and chronic pain secondary to inflammation. As a greater understanding of the risks of gastrointestinal (GI), cardiovascular (CV) and renal events with NSAIDs use has emerged, guidelines have evolved to reflect differences in risks among NSAIDs. Updated guidelines have yet to reflect new evidence from recent trials which showed similar CV event rates with celecoxib compared to naproxen and ibuprofen, and significantly better GI tolerability for celecoxib. This practice advisory paper aims to present consensus statements and associated guidance regarding appropriate NSAID use based on a review of current evidence by a multidisciplinary group of expert clinicians. This paper is especially intended to guide primary care practitioners within Asia in the appropriate use of NSAIDs in primary care. Following a literature review, group members used a modified Delphi consensus process to determine agreement with selected recommendations. Agreement with a statement by 75% of total voting members was defined a priori as consensus. For low GI risk patients, any nonselective NSAID plus proton pump inhibitor (PPI) or celecoxib alone is acceptable treatment when CV risk is low; for high CV risk patients, low-dose celecoxib or naproxen plus PPI is appropriate. For high GI risk patients, celecoxib plus PPI is acceptable for low CV risk patients; low-dose celecoxib plus PPI is appropriate for high CV risk patients, with the alternative to avoid NSAIDs and consider opioids instead. Appropriate NSAID prescription assumes that the patient has normal renal function at commencement, with ongoing monitoring recommended. In conclusion, appropriate NSAID use requires consideration of all risks.

Non-Steroidal Anti-Inflammatory Drugs in the Elderly. Agreement With Safe Prescription Recommendations According to Cardiovascular and Gastrointestinal Risks.

Non-Steroidal Anti-Inflammatory Drugs are the cornerstone in the treatment of acute and chronic pain due to inflammation in musculoskeletal conditions. Even though adverse side-effects are associated, their use is common in the elderly patients. Our aim is to determine the prescription trend of NSAIDs, the evaluation for gastrointestinal (GI) and cardiovascular (CV) risks, and the level of agreement with prescription guidelines. We conducted an observation and descriptive study in a general hospital geriatrics consultation. From the 231 patients only 59 patients had a NSAIDs prescription. The most frequently prescribed was Acetaminophen, in 29(49.1%) patients, Celecoxib was prescribed in 11(18.6%) patients, Piroxicam in 5(8.4%) patients, Acetaminophen plus Celecoxib plus Omeprazole in 4 (6.7%), Acetaminophen plus Piroxicam in 2 (0.3%) patients, and Acetaminophen plus Diclofenac plus Celecoxib in 1 patient (1.6%). In the Framingham risk classification there were 160/231 (69.3%) patients in Very High Risk and 71/231 (30.7%) patients in High Risk. There were no patients in Low Risk. GI Risk: 79 patients (34.1%) had a peptic ulcer disease history. There were 55/231 (23.8%) in the High GI Risk classification, 102/231 (44.1%) in Intermediate GI Risk and 74/231 (32%) in the Low Risk. The level of agreement between the prescribed versus recommended NSAIDs according the CV and GI risks was measured with a contingence table and the kappa statistic of 0.37 p=0.001. There is a low level of agreement between prescribed and recommended NSAID in elderly population.

Prevalence of Gastrointestinal and Cardiovascular Risk in Patients with Degenerative Lumbar Spinal Disease.

BackgroundLimited information is available about the proportion of patients with degenerative lumbar spinal disease (DLSD) who have gastrointestinal (GI) and cardiovascular (CV) risk factors. Many DLSD patients are prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) that are known to carry risks to the GI and CV systems by increasing GI bleeding and thromboembolic events. This study aimed to measure the prevalence of GI and CV risk in patients with DLSD and to ascertain whether the prescription of NSAIDs is in line with current guidelines.MethodsThis study included 153 patients with symptomatic DLSD who were planning to undergo lumbar spinal surgery. The GI profile was checked using the GI Standardized Calculator of Risk for Event system and CV risk was evaluated using the presence of metabolic syndrome. The conformity of the prescription of NSAIDs was investigated according to the recommendations in current guidelines.ResultsMore than half of the patients (59.5%) had high or very high GI risk, and 66% of the patients were diagnosed with metabolic syndrome, which corresponds with CV risk. The rate of simultaneous GI and CV risk was 40.5% (n = 62 / 153; gastrointestinal Standardized Calculator of Risk for Event, > high and metabolic syndrome, yes). The actual prescription of NSAIDs was not in accordance with current guidelines.ConclusionsTwo out of 3 patients had GI or CV risk factors, and approximately 40% of patients had both. Detailed assessment of GI and CV risk in patients with DLSD by using effective evaluation tools is mandatory for optimal medical treatment.

Gastrointestinal risk factors and patient-reported outcomes of ankylosing spondylitis in Korea.

AimThis study examined the degree of gastrointestinal (GI) risk and patient‐reported outcomes including GI‐related symptoms, adherence to non‐steroidal anti‐inflammatory drugs (NSAIDs), disease activity and quality of life (QoL) in patients with ankylosing spondylitis (AS).MethodsCross‐sectional, observational study conducted at six nationwide, university‐based hospitals of Korea. AS patients treated with NSAIDs for at least 2 weeks were included between March and September 2016. Demographic and clinical data were gathered through a medical chart review and patient survey. GI risk was estimated using Standardized Calculator of Risk for Events (SCORE). NSAIDs adherence was investigated with Morisky Medication Adherence Scale‐8 (MMAS‐8). Disease activity and QoL were examined with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and EuroQol‐3L (EQ‐5D, EQ‐visual analog scale [EQ‐VAS]), respectively. Path analysis was implemented to estimate pathways of GI risk, GI symptoms and NSAIDs adherence to QoL.ResultsA total of 596 patients (age: 38.9 ± 12.6 years, male: 82.1%) participated in the study, of which 33.2% experienced GI symptoms during NSAID treatment, and 34.2% of them showed ongoing GI symptoms upon enrollment. According to SCORE, 37.1% of patients showed moderate to very high GI risk. No patient showed high adherence according to MMAS‐8, so 55.3% of patients with moderate adherence were considered adherent. BASDAI and QoL of the total patients were 3.5 ± 2.0, 0.6 ± 0.3 (EQ‐5D), and 67.4 ± 19.8 (EQ‐VAS), respectively. From path analyses, higher GI risk significantly lowered QoL.ConclusionThis study suggests timely therapeutic strategies should be implemented to manage GI risk during NSAID treatment in order to effectively manage AS.

Coxibs Refocus Attention on the Cardiovascular Risks of Non-Aspirin NSAIDs.

Non-steroidal anti-inflammatory drugs (NSAIDs) were differentiated from steroidal anti-inflammatory medicines to help clinicians who needed to use anti-inflammatory agents that were safer than steroids. With market entry of rofecoxib in 1999, NSAIDs were then further classified into traditional NSAIDs and cyclooxygenase (COX)-2 inhibitors (coxibs), the latter posing potentially fewer gastrointestinal risks. In 2005, rofecoxib was withdrawn from the market because of concerns about the risk of heart attack and stroke with long-term use, and clinical practice began focusing more on the cardiovascular versus gastrointestinal safety of coxibs. Since then, many coxibs have remained unapproved by the US FDA or have been removed from the market. This article explains how coxibs refocused attention on the cardiovascular safety of NSAIDs and the general implications of that. COX-2 activity/specificity is one factor associated with increased cardiovascular risks; however, these risks cannot be attributed to coxibs alone. The traditional NSAIDs (i.e., meloxicam, etodolac, and nabumetone) have significant COX-2 specificity, but naproxen and ibuprofen have less specificity. All NSAIDs, whether traditional or a coxib, pose some cardiovascular risks. It is possible that clinicians continue to focus more on decreasing the immediate gastric risks than preventing the later cardiovascular risks. The cardiovascular risks posed by NSAIDs should not be disregarded for the sake of achieving gastrointestinal benefits. Current recommendations suggest NSAIDs should be considered a single class of non-aspirin NSAIDs. Preferred NSAIDs are ibuprofen and naproxen. Coxibs are preferred in patients with low cardiovascular risk and high gastrointestinal risk who are intolerant to anti-dyspepsia therapy.

Epidemiology of Upper Gastrointestinal Damage Associated with Low-Dose Aspirin.

Low-dose aspirin, commonly defined as 75-325 mg daily, is widely used for cardiovascular (CV) protection. It reduced the risk of CV events and death in patients with coronary and cerebrovascular diseases and has the advantages of both low cost and long duration of antiplatelet action. However, low-dose aspirin therapy is associated with upper gastrointestinal (GI) side effects, which range from dyspepsia (point prevalence: 31%), gastroduodenal erosions (point prevalence: 60%), endoscopic peptic ulcer (3-month incidence: 7%) to symptomatic or complicated ulcers (annual incidence of upper GI bleeding: 0.6%; relative risk of upper GI bleeding: 2.6). The important factors that increase the risk of low-dose aspirin-related ulcer complications include a history of bleeding peptic ulcer, prior peptic ulcer, age > 70 years, H pylori infection, and concomitant drug therapy with non-steroidal anti-inflammatory drugs, other antiplatelet agents (e.g., clopidogrel) or anticoagulants. The use of enteric-coated or buffered preparations do not reduce the risk of upper GI complications. Assessment of GI risk for patients is a crucial step in preventing complications of antiplatelet agents. Patients with a high GI risk should prevent peptic ulcer or ulcer complications by co-therapy with an antisecretory agent, especially proton pump inhibitors. H pylori eradication is recommended for patients requiring long-term low-dose aspirin therapy who have a prior history of peptic ulcer or GI bleeding.

ASSESSMENT OF RISK FOR GASTROINTESTINAL AND CARDIOVASCULAR COMPLICATIONS ASSOCIATED WITH THE USE OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS IN THE CIS POPULATION: PRELIMINARY DATA OF THE CORONA-2 EPIDEMIOLOGICAL SURVEY

Nonsteroidal anti-inflammatory drugs (NSAIDs) are able to effectively control the major symptoms of rheumatic diseases and widely used in real clinical practice. However, they may cause serious gastrointestinal (GI) and cardiovascular (CV) events. The prevention of these events is based on the estimation of whether risk factors (RFs) are present. Objective: to estimate the presence of RFs in patients needing NSAIDs. Subjects and methods . A cross-sectional epidemiological survey was performed, during which 2021 physicians from 9 CIS countries questioned for 2 weeks at least 10 patients needing NSAIDs. The inclusion criterion was severe musculoskeletal pain (>40 mm on a 100-mm visual analogue scale (VAS)) or use of NSAIDs at the examination. Data were obtained on 21,185 patients (57.5% women and 42.5% men) (mean age 50.5±14.1 years) who had predominantly dorsalgia (56.6%) and osteoarthritis (23.5%). The mean pain value was 62.2±25.2 mm. Results. 1.7, 11.3, and 25.3% of patients had history of gastrointestinal bleeding, ulcer, or dyspepsia, respectively; people over 65 years of age constituted 16.8%; those who took low-dose aspirin (LDA) – 20.0%. The total number of patients at high risk for GI events was 29.0%. There were also common CV RFs: myocardial infarction or stroke (7.8%), coronary heart disease (17.8%), hypertension (37.7%), and diabetes mellitus (8.1%). The total number of patients at high risk for CV events (without SCOR assessment) was 23.0%. Many high-risk patients who has already used NSAIDs received no effective prevention. Thus, 62.2% of the patients at high GI risk took gastroprotective drugs; 53.2% of those at high CV risk used LDA. Conclusion. A large number of patients needing active analgesic therapy have a serious risk for drug-induced complications. This limits the possibility of using NSAIDs and determines the need for effective prevention or use of alternative methods for analgesia.

Clinical management of patients with hip and knee osteoarthritis: patient satisfaction with treatment switch

Hip and knee osteoarthritis (OA) is a common cause of disability, with great quality of life and economic impact, hence the need for effective treatment. Patient satisfaction with treatment is a measure of therapeutic effectiveness and may be used to assess treatment switch in OA patients. A 3-month multicenter, prospective, epidemiologic, non-interventional study was conducted in patients with hip and/or knee OA to assess therapeutic efficacy in patients requiring treatment switch due to lack of effectiveness and/or tolerability in primary care settings. Therapeutic effectiveness was assessed by patient satisfaction using the osteoARthritis Treatment Satisfaction (ARTS) scale. The 3-month disease change [by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and a pain visual analog scale (VAS)] and its correlation with treatment satisfaction were also assessed, as well as patient gastrointestinal (GI) and cardiovascular (CV) profiles. 5,976 patients were analyzed (mean age 68.8 years, 65.1 % female). 67 and 61.8 % showed high GI and CV risk, respectively. The proportion of patients on acetaminophen treatment during the study decreased from 74.8 % at baseline to 23.9 %, while the proportion on non-steroidal anti-inflammatory drugs (NSAIDs) increased from 59.8 to 85.8 %. At 3 months, the standardized (0-100) overall ARTS score increased from 57.7 to 71.6 (p < 0.0001), while disease severity decreased. There was a significant (p < 0.0001) negative association between the ARTS, and the WOMAC and VAS scores. Treatment switching from acetaminophen to NSAIDs as a consequence of poor effectiveness and/or tolerability resulted in increased patient satisfaction with treatment and lower OA severity.

Celecoxib and Diclofenac Plus Omeprazole are Similarly Effective in the Treatment of Arthritis in Patients at High GI Risk in the CONDOR Trial§

Objective: Compare effectiveness of celecoxib versus diclofenac plus omeprazole in improving arthritis signs and symptoms in patients at high gastrointestinal (GI) risk who were enrolled in the CONDOR (Celecoxib vs Omeprazole and Diclofenac in Patients With Osteoarthritis and Rheumatoid Arthritis) trial.Methods: CONDOR was a 6-month, prospective, double-blind, triple-dummy, parallel-group, randomized, multicenter trial comparing celecoxib 200 mg twice daily versus diclofenac slow release (SR) 75 mg twice daily plus omeprazole 20 mg daily. Patients were Helicobacter pylori negative, had osteoarthritis (OA) or rheumatoid arthritis (RA), were aged ≥60 years, were with or without a history of gastroduodenal ulceration, or were ≥18 years with previous gastroduodenal ulceration. Patients’ Global Assessment of Arthritis was determined at each study visit.Results: A total of 4484 patients were randomized to treatment (2238 celecoxib, 2246 diclofenac SR) and included in the intention-to-treat analyses. Least squares mean (LSM) (standard error [SE]) for Patients’ Global Assessment of Arthritis was 3.219 (0.017) and 3.221 (0.017) at baseline for celecoxib and diclofenac SR (p=0.90). Improvement in both groups was similar in months 2, 4, and 6; at month 1 the LSM (SE) was 2.647 (0.017) and 2.586 (0.017) for celecoxib and diclofenac (p=0.0025). LSM difference (SE) from baseline to final visit demonstrated an improvement of 0.75 (0.02) in celecoxib-treated patients and 0.77 (0.02) in diclofenac SR-treated patients (p=0.42).Conclusions: Celecoxib and diclofenac plus omeprazole were shown to have similar efficacy in patients with OA and/or RA at increased GI risk who were enrolled in the CONDOR trial.Trial Registry: Trial was registered under ClinicalTrials.gov identifier NCT00141102.

Effect of Baseline Gastrointestinal Risk and Use of Proton Pump Inhibitors on Frequency of Discontinuation of Aspirin for Secondary Cardiovascular Prevention in United Kingdom Primary Care

For patients at high cardiovascular and high gastrointestinal (GI) risk, coprescription of a proton pump inhibitor (PPI) with low-dose aspirin is recommended. We aimed to quantify the extent to which low-dose aspirin discontinuation in patients at high cardiovascular risk is affected by PPI use and baseline GI risk. Patients aged 50 to 84 years who had evidence of ischemic heart disease or cardiovascular disease and who were new users of low-dose aspirin in 2000 to 2007 were identified using The Health Improvement Network (n= 35,604). Aspirin discontinuation was defined as a period of at least 90 days after completion of the last prescribed course during which no repeat prescription was issued. The incidence of low-dose aspirin discontinuation was 26.8 per 100 person-years (95% confidence interval [CI] 26.2 to 27.4). The age-, gender-, and indication-adjusted risk of aspirin discontinuation was 15% less among continuous PPI users than among PPI nonusers (hazard ratio [HR] 0.85, 95% CI 0.78 to 0.92); after further adjusting for number of coprescribed medications, the HR was 0.95 (95% CI 0.87 to 1.03). Continuous PPI use was associated with a reduced risk of aspirin discontinuation among patients at high GI risk (HR 0.83; 95% CI 0.74 to 0.93) but not among those at low GI risk (HR 1.08; 95% CI 0.96 to 1.21). In conclusion, among patients at high GI risk, concomitant users of aspirin and PPI showed a greater aspirin adherence than aspirin users not on PPI. Further studies need to confirm factors with the potential to increase adherence to long-term aspirin.

The Impact of Lack of Pharmacist Contribution on the Prescription Patterns and the Appropriateness of Indications of NSAIDs : A Cross-Sectional Study

Purpose: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used medications worldwide. However, recent literature strongly points to gastrointestinal (GI) and cardiovascular (CV) risks associated with NSAIDs use. The current study was carried out in Jordan University Hospital. The main objective was to evaluate the role of pharmacists in directing the current prescription patterns and appropriateness of NSAID therapiesto establish strategies for medication reconciliation in the healthcare systems in the region. Methods: This is a prospective cross-sectional qualitative study that enrolled a total of 400 patients over a period of 10 months. The NSAID use was evaluated in patients with and without established CVD and various GI risk stratifications. In addition, 30 physicians were recruited into the study to determine the current prescription patterns. A structured questionnaire was validated and handed to physicians to determine strengths and weaknesses in the current system. NSAID-related drug interactions were evaluated in 200 of the patients. Results: Sixty five percent of the patients without CVD were at moderate GI risk and 12% were at high risk. Sixty nine percentof patients with CVD were at high GI risk and 28% were at moderate risk. Pharmacists were not involved in decision therapies pertaining to NSAIDs, which led to serious drug-related problems in the therapeutic regimens for patients using the NSAIDs.In 64% of the patients without CVD, NSAID therapy did not meetthe recommendations of current guidelines. There was no drug therapy monitoring or patient counseling by a proficient clinical pharmacist, whichled to virtually no identification of potential drug interactions or optimization of medication therapy. Conclusions: The study unraveleda great opportunity to improve the clinical outcomes in patients on NSAID therapy. The lack of pharmacist involvement puts patients at major health risks. Updating physicians on practice guidelines, including a clinical pharmacist in therapy decisions, and modifying hospital formularies are the most urgent recommendations.

OP0187-PC Potentially harmful prescription of NSAIDS in a primary care population with musculoskeletal complaints

BackgroundTo reduce adverse drug events (ADEs), clinical guidelines recommend cautious prescription of non-steroidal anti-inflammatory drugs (NSAIDs) in patients known to be at a high risk of developing a serious ADE....

Spaced administration of PA32540 and clopidogrel results in greater platelet inhibition than synchronous administration of enteric-coated aspirin and enteric-coated omeprazole and clopidogrel

A common regimen for patients requiring dual-antiplatelet therapy who are at risk for gastrointestinal complications is the synchronous administration of enteric-coated (EC) aspirin, a proton pump inhibitor, and clopidogrel, although proton pump inhibitors have the potential for pharmacodynamic interaction with clopidogrel. Spaced administration of a clopidogrel and a single-tablet formulation of aspirin and immediate-release omeprazole (PA32540) was considered as an alternative that might reduce this potential pharmacodynamic interaction. A randomized, open-label, crossover study was conducted in healthy subjects (n = 30). Two 7-day treatments were separated by 14-day washout periods: (a) PA32540 + clopidogrel (300 mg loading/75 mg maintenance) 10 hours later and (b) synchronous dosing of clopidogrel + EC aspirin (81 mg) + EC omeprazole (40 mg). The primary end point was the inhibition of platelet aggregation (20 μM adenosine diphosphate, maximal extent) after 7 days. CYP2C19 and ABCB1 genotypes were determined. Inhibition of platelet aggregation was greater with spaced PA32540 + clopidogrel therapy vs synchronous clopidogrel + EC aspirin + EC omeprazole therapy (P = .004). There was no difference in day 7 arachidonic acid-induced aggregation. The effect of spacing on pharmacodynamics was independent of genotype. PA32540 and clopidogrel spaced 10 hours apart had greater antiplatelet effects than did synchronously administered EC aspirin (81 mg), clopidogrel (75 mg), and EC omeprazole in healthy volunteers. These finding are directly relevant to the treatment for patients with high gastrointestinal risk who require dual-antiplatelet therapy and gastroprotection.

An evaluation of the impact of NICE guidelines regarding COX-2 selective inhibitors on GP prescribing

Abstract Focal points

Prescription Pattern of NSAIDs and the Prevalence of NSAID-induced Gastrointestinal Risk Factors of Orthopaedic Patients in Clinical Practice in Korea

This is a cross-sectional observational study undertaken to explore the current prescription pattern of non-steroidal anti-inflammatory drugs (NSAIDs) and the prevalence of NSAID-induced gastrointestinal (GI) risk factors of orthopaedic patients in real clinical practice in Korea. Study cohort included 3,140 orthopaedic outpatients at 131 hospitals and clinics between January 2008 and August 2008. A self-administered questionnaire was completed by each patient and physician. A simplified risk scoring scale (the Standardized Calculator of Risk for Events; SCORE) was used to measure patients' risk for GI complications. The pattern of NSAIDs prescription was identified from medical recordings. Forty-five percents of the patients belonged to high risk or very high risk groups for GI complications. The cyclooxygenase-2 enzyme (COX-2) selective NSAID showed a propensity to be prescribed more commonly for high/very high GI risk groups, but the rate was still as low as 51%. In conclusion, physician's considerate prescription of NSAIDs with well-understanding of each patient's GI risk factors is strongly encouraged in order to maximize cost effectiveness and to prevent serious GI complications in Korea. Other strategic efforts such as medical association-led education programs and application of Korean electronic SCORE system to hospital order communication system (OCS) should also be accompanied in a way to promote physician's attention.

Use of Nonsteroidal Antiinflammatory Drugs: Is There a Change in Patient Risk Profile After Withdrawal of Rofecoxib?

Use of traditional nonsteroidal antiinflammatory drugs (tNSAID) increased after rofecoxib withdrawal. tNSAID use is associated with increased gastrointestinal (GI) toxicity and cardiovascular (CV) risk similar to celecoxib. The objective of our study was to describe changes in celecoxib and tNSAID use regarding GI and CV risk and congestive heart failure (CHF) and renal risk that occurred in Quebec, Canada, between April 2005-March 2007 (the post-period) compared to April 2002-March 2004 (the pre-period). Data were obtained from the provincial health insurance agency. All NSAID users ≥ 50 years of age were considered. Celecoxib use decreased by 23% (coxib 61%) while that of tNSAID doubled. In both periods, celecoxib users were older and included more women, and they suffered more frequently from arthritis. Users of celecoxib were more likely to have higher level of GI risk: post-period odds ratios compared to low GI risk, very high 1.79 (95% CI 1.63, 1.97), high 1.76 (95% CI 1.71, 1.81), and moderate 1.30 (95% CI 1.27, 1.33); similar results were observed in the pre-period. Celecoxib users had higher CV risk levels in the pre-period: OR compared to low CV risk, very high 1.13 (95% CI 1.08, 1.19), high 1.24 (95% CI 1.20, 1.29), and moderate 1.16 (95% CI 1.14, 1.19); and in the post-period, very high 0.85 (95% CI 0.81, 0.89), high 1.13 (95% CI 1.10, 1.16), and moderate 1.15 (95% CI 1.12, 1.17). CHF and renal risk factors did not play an important role in the choice of NSAID in either period. Current NSAID use differs from that prior to 2004. Coxib utilization decreased substantially and patients at high CV risk seem less likely to receive celecoxib, while those at high GI risk seem more likely to receive it.

T1135 The Complementary Role of Impedance Color Contours for Analysis of Impedance-pH Tracings During Esophageal Reflux Monitoring

Medical management of adults with osteoarthritis (OA) who require non-steroidal anti-inflammatory drugs (NSAIDs) must be decided after assessing gastrointestinal (GI) and cardiovascular (CV) risks in the individual patient. Aim: To evaluate the gastrointestinal and cardiovascular risk profile of OA patients who require NSAIDs. Methods: We conducted a transversal, multicenter and observational study in consecutive patients with OA who were considered candidates for NSAID treatment and were visited by 374 unselected rheumatologists throughout the National Health System. Patients were classified into three risk groups (low, moderate and high) for their GI and CV characteristics. These were defined attending to the presence of a number of well-established GI risk factors (Lanas & Hunt, Ann Med 2006; 38, 415-28) or to the application of the European SCORE model (Conroy et al. 2003; EurHeart J 24, 987-1003) for assessing the overall risk for cardiovascular disease, respectively. Results: The study sample was composed of 3293 patients; mean age was 64.7±10.9 years, the majority of whom were women (73.2%). The mean time from diagnosis was 5.4 years, with 66.6% of the patients diagnosed with axial OA of the spine and 81.1% with peripheral OA of the hand, hip and knee. Most patients (86.6%) (2880/3248) were at increased GI risk, and a significant number (22.3%) (724/3248) were at high GI risk. The CV risk was high in 44.2% of the patients (1440/3261), moderate in 19.9% (648/3261) and low in 36% (1173/3261). Only 26.4% of those at high CV risk were on ASA, whereas 22.7% of all ASA users (104/457) were taking concomitantly Ibuprofen. Overall, 15.5% (504/3248) of patients presented a very high-risk profile, having both high GI and CV risks. The type of NSAID prescription was similar regardless of the associated GI and CV risk profile. Conclusion: Most patients with osteoarthritis requiring NSAIDs for pain control showed a high prevalence of GI and CV risk factors. Over half of the patients were at either high GI or CV risk or both, such that the prescription of OA treatments should be very carefully considered.