The safety of endoscopic sphincterotomy in patients receiving antiplatelet agents: a case-control study.

OBJECTIVE: To determine whether antiplatelet agents are associated with endoscopic sphincterotomy-related haemorrhage as few well-controlled data exist on this controversial issue. METHODS: A case-control study in a tertiary care setting included cases with bleeding following endoscopic sphincterotomy, matched with 2-3 controls selected according to age +/- 15 years, sex, and procedural date+/- 2 years. Cases and controls were compared for possible risk factors of postendoscopic sphincterotomy bleeding (presence of a coagulopathy and cholangitis). The main outcome measurement was the association between the use of antiplatelet medications and postendoscopic sphincterotomy bleeding after adjustment for possible confounding. RESULTS: The 40 cases [mean age 68 +/- 17 (s.d.) years, 50% female] and 86 controls [68 +/- 16 years, 50% female] were comparable except for differences noted in International Normalized Ratio (INR) (>2 in four cases vs. two controls), and pre-endoscopic sphincterotomy cholangitis (45% vs. 20%). Amongst cases, 13% were on aspirin and 3% on clopidogrel; 17% of controls took aspirin, and 4% a non-steroidal anti-inflammatory drug. 53% of cases bled immediately; the remainder haemorrhaged at 2 +/- 3 days. After adjustment for an elevated INR and cholangitis, exposure to antiplatelet agents was not significantly associated with procedure-related bleeding (odds ratio = 0.41, 95% CI [ 0.13; 1.31]). CONCLUSION: This case-control study provides controlled data suggesting that antiplatelet agents do not significantly increase the risk of clinically-important bleeding related to endoscopic sphincterotomy. The low prevalences of non-steroidal anti-inflammatory drugs and clopidogrel use limit any definite conclusion on their elective use before endoscopic sphincterotomy.

Hospitalization for gastrointestinal bleeding associated with non-steroidal anti-inflammatory drugs among elderly patients using low-dose aspirin: a retrospective cohort study.

OBJECTIVES: Many elderly patients are prescribed both low-dose aspirin (ASA), for cardiovascular protection and non-steroidal anti-inflammatory drugs (NSAIDs) for pain control. Compared with non-selective NSAIDs (NS-NSAIDs), celecoxib has a superior gastrointestinal (GI) safety profile in general. It is unclear, however, whether this fact holds good among patients taking ASA. We compared GI hospitalization rates among elderly patients taking celecoxib, NS-NSAIDs, celecoxib and ASA or NS-NSAIDs and ASA. METHODS: This was a retrospective cohort study using Quebec government databases. All patients 65 yrs of age or older who filled a prescription for celecoxib or an NS-NSAID between April 1999 and December 2002 were included. Cox regression models were used to compare the GI hospitalization rates between the four exposure categories adjusting for potential confounders. RESULTS: A total of 332 491 patients were included. Among 1 522 307 celecoxib prescriptions, 430 214 were filled by patients concurrently receiving ASA (celecoxib and ASA); 195 369 of 863 646 NS-NSAID prescriptions were filled by patients receiving ASA (NS-NSAID and ASA). Celecoxib without ASA was less likely than NS-NSAID without ASA to be associated with GI hospitalization [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.33-0.50]; celecoxib and ASA was also less likely to be associated with GI hospitalization than NS-NSAID and ASA (HR 0.62, 95% CI 0.48-0.80); GI hospitalization rates were similar for celecoxib and ASA and NS-NSAID without ASA (HR 1.01, 95% CI 0.81-1.25). CONCLUSION: Among elderly patients receiving cardiovascular protection with ASA and pain control with anti-inflammatory drugs, celecoxib may be safer with regards to GI toxicity than NS-NSAIDs.

Therapy switching and associated costs in elderly patients receiving COX-2 selective inhibitors or non-selective non-steroidal anti-inflammatory drugs in Quebec, Canada.

OBJECTIVES: Lack of efficacy or tolerability of some non-steroidal anti-inflammatory drugs (NSAIDs) may lead to switching between non-selective NSAIDs (nsNSAIDs) and cyclooxygenase-2 (COX-2) selective inhibitors (coxibs), potentially increasing treatment costs due to additional physician visits and wastage of medication. This study assessed drug switching and associated costs among elderly chronic NSAID users. METHODS: Data for patients who filled their first prescription for a coxib or nsNSAID in 2001 were obtained from the Quebec Health Insurance Agency. Follow-up was terminated at the earliest of: 1 yr, the first day without NSAID exposure following the index filling date, or death. Patients could switch NSAIDs several times during follow-up. Person-days of exposure were categorized by the NSAID most recently dispensed: rofecoxib, celecoxib, Arthrotec(R) or non-Arthrotec (nA) nsNSAID. Cox regression models compared time to switch between groups, adjusting for patient baseline characteristics. Upon a switch, pills remaining from the previous prescription were considered wasted. The costs of wasted pills and switch-associated physician visits were estimated. RESULTS: Throughout follow-up, patients filled 38 267 prescriptions for rofecoxib, 31 282 for celecoxib, 1108 for Arthrotec and 4388 for nA-nsNSAIDs. Adjusted hazard ratios (95% confidence interval) for switching versus nA-nsNSAIDs were: rofecoxib, 0.39 (0.35-0.44); celecoxib, 0.43 (0.38-0.48). Compared with nA-nsNSAID prescriptions, adjusted switching-related healthcare costs were 53 and 47% lower on average for rofecoxib and celecoxib prescriptions, respectively. These costs were 34% higher for Arthrotec prescriptions than for nA-nsNSAIDs. CONCLUSIONS: Compared with recipients of nsNSAIDs, coxib recipients were less likely to switch medications and had approximately half the adjusted costs for switching-related wasted resources per prescription.

Meta-analysis: proton-pump inhibition in high-risk patients with acute peptic ulcer bleeding.

BACKGROUND: Recent data suggest that profound acid suppression may improve outcomes of patients in peptic ulcer bleeding. AIM: To better characterize the role of different pharmacological therapies in this population. METHODS: MEDLINE was used to identify randomized trials (01/1990-04/2003) that assessed the efficacy of pharmacological treatments for patients with bleeding peptic ulcers exhibiting high-risk stigmata (Forrest Ia-IIb). Three groups of treatment were assessed: proton-pump inhibitors given as high-dose bolus followed by intravenous constant infusion (40-80 mg and at least 6 mg/h), high-dose oral proton-pump inhibitors (at least twice the standard dosage), non-high-dose proton-pump inhibitors (other proton-pump inhibitors dosing schedules). Mixed-effect models were used to determine rate differences between treatment and control groups. RESULTS: Eighteen studies (1855 patients) were included. High-dose intravenous proton-pump inhibitors significantly reduced rebleeding (-14.6%), surgery (-5.4%) and mortality (-2.7%) compared with placebo, and rebleeding (-20.6%) compared with H(2)RA. Compared with placebo, high-dose oral proton-pump inhibitors significantly reduced only rebleeding (-11.8%), while non-high-dose proton-pump inhibitor treatment significantly improved all three outcomes. CONCLUSIONS: High-dose intravenous proton-pump inhibitor significantly decreases ulcer rebleeding, surgery and mortality. Early data on high-dose oral proton-pump inhibitor suggest improved rebleeding. The non-high-dose proton-pump inhibitor regimens, including a broad range of dosing, also improved outcomes, suggesting that doses inferior to those in the high-dose intravenous proton-pump inhibitor may be effective.