Concomitant NSAID Research Articles

Incidence of Thrombotic Cardiovascular Events in Patients Taking Celecoxib Compared with Those Taking Rofecoxib

Rofecoxib was withdrawn from the market worldwide because of concerns relating to cardiovascular safety. There is conflicting evidence as to whether celecoxib, the most popular alternative to rofecoxib, carries the same cardiovascular risks. This study's aim was to compare the incidence of thrombotic cardiovascular events in patients taking celecoxib with patients taking rofecoxib. Prescription event monitoring methodology was used in this prospective, longitudinal, observational cohort study, in which cohorts of patients were established from prescription data and thrombotic cardiovascular events were identified from follow-up questionnaires to patients' doctors and other sources. New Zealand patients with at least one prescription for either rofecoxib or celecoxib between 1 December 2000 and 30 November 2001. For this interim analysis the total cohorts were separated into three groups at different stages of follow-up: complete, incomplete and no follow-up. Cox's proportional hazards models were applied to calculate hazard ratios for celecoxib compared with rofecoxib. The total cohorts included 26,403 patients receiving rofecoxib and 32,446 patients receiving celecoxib. 4882 (18%) rofecoxib and 6267 (19%) celecoxib patients had been completely followed up. In this group the unadjusted hazard ratio for celecoxib compared with rofecoxib was 1.07 (95% CI 0.59, 1.93). After adjustment for age this hazard ratio was 0.94 (95% CI 0.51, 1.70). Further adjustment for sex, 'as required' use, indication for use, concomitant NSAID use and pre-existing cardiovascular disease resulted in only minor changes to the hazard ratio. This interim analysis of the Intensive Medicines Monitoring Programme data suggests that in 'real-life' postmarketing use in New Zealand there is no significant difference in the risk of cardiovascular thrombotic events in patients taking celecoxib compared with those taking rofecoxib.

NSAID-Induced Peptic Ulcers and Helicobacter pylori Infection

The conflicting data about the influence of Helicobacter pylori infection on the ulcer risk in patients receiving NSAIDs can be accounted for by the heterogeneity of study designs and the diversified host response to H. pylori. Factors that will affect the outcome include the choice of H. pylori diagnostic tests, previous ulcer complications, concurrent use of acid suppressants, NSAID-naive versus long-term users, low-dose aspirin (acetylsalicylic acid) versus non-aspirin NSAIDs and whether the result was derived from a pre-specified endpoint or post hoc subgroup analysis. Current evidence suggests that H. pylori eradication reduces the ulcer risk for patients who are about to start receiving NSAIDs but not for those who are already on long-term NSAID therapy. Since treatment with a proton pump inhibitor (PPI) worsens H. pylori-associated corpus gastritis, H. pylori should be tested for, and eradicated if present, before starting long-term prophylaxis with PPIs. Patients with H. pylori infection and a history of ulcer complications who require NSAIDs should receive concomitant PPIs or misoprostol after curing the infection. Among patients receiving low-dose aspirin, who have H. pylori infection and previous ulcer complications, long-term treatment with a PPI further reduces the risk of complicated ulcers if H. pylori eradication fails or if patients use concomitant non-aspirin NSAIDs. Current data on the gastric safety of COX-2 selective NSAIDs in H. pylori-infected patients are conflicting. Limited data suggest that the gastroduodenal sparing effect of rofecoxib is negated by H. pylori infection in patients who have had prior upper gastrointestinal events. In light of potential cardiovascular risk with COX-2 selective NSAIDs, it is important to weigh the potential adverse effects against the benefits for an individual patient.

Acute Treatment of Facet Syndrome by CT-Guided Injection of Dexamethasone-21-Palmitate???Alone and in Combination with Mepivacaine

To compare the efficacy and tolerability of dexamethasone-21-palmitate and mepivacaine alone and in combination in the acute treatment of facet syndrome. A total of 157 patients requiring acute therapy for lumbar facet syndrome were treated with computed tomography (CT)-guided intra-articular infiltration of either an anti-inflammatory corticosteroid, a local anaesthetic or a combination of the two. Patients assigned to the first treatment group (n = 60) received the corticosteroid dexamethasone-21-palmitate (Lipotalon((R))); patients in the second group (n = 36) received the local anaesthetic mepivacaine (Meaverin((R))); patients in the third group (n = 61) received a combination of the two drugs. The study duration was from November 2002 until June 2003. In all three groups, values for compression pain, stress pain and rest pain improved significantly from baseline within 1 hour of injection: in the dexamethasone monotherapy group there was a 13% reduction in compression pain, 20% reduction in stress, and 22% reduction in rest pain; in the groups that received mepivacaine only or a combination of the two drugs there was a 63% and 60%, respectively, reduction of compression pain, 81% and 83%, respectively, reduction of stress pain, and 84% and 77%, respectively, reduction of rest pain. After 72 hours, improvements in these variables were significantly greater in patients treated with dexamethasone-21-palmitate (either as monotherapy or in combination therapy) than in patients treated with mepivacaine alone. In both groups treated with dexamethasone palmitate there was a 57% and 64%, respectively, reduction of compression pain, 70% and 66%, respectively, reduction of stress pain, and 75% and 64%, respectively, reduction of rest pain. In the mepivacaine monotherapy group there was a 17% reduction in compression pain, 26% reduction in stress pain and 13% reduction in rest pain. Both physicians and patients also rated the dexamethasone-21-palmitate-containing regimens as more effective than mepivacaine alone at 72 hours. Over the entire observation period, combination therapy was, on average, superior to both monotherapy regimens. The proportion of patients using concomitant NSAID medication after 3 days was reduced by 50% in the mepivacaine group and by 76% and 100%, respectively, in the dexamethasone-21-palmitate and combination therapy groups. CT-guided infiltration treatment was well tolerated and was associated with virtually no side effects in this study. CT-guided infiltration of dexamethasone palmitate, particularly in combination with mepivacaine, represents a safe and effective method for the acute therapy of lumbar facet syndrome. The combination is superior to the local anaesthetic alone with regard to pain reduction up to 3 days after injection.

Upper gastrointestinal tolerability of once-weekly alendronate 70 mg with concomitant NSAID use

Upper gastrointestinal tolerability of once-weekly alendronate 70 mg with concomitant NSAID use

Upper GI tolerability of once-weekly alendronate 70 mg with concomitant NSAID use

Upper GI tolerability of once-weekly alendronate 70 mg with concomitant NSAID use

Concomitant overdosing of other drugs in patients with paracetamol poisoning.

Paracetamol is frequently involved in intended self-poisoning, and concomitant overdosing of other drugs is commonly reported. The purpose of the study was to investigate further concomitant drug overdose in patients with paracetamol poisoning and to evaluate its effects on the outcome of the paracetamol intoxication. Six hundred and seventy-one consecutive patients admitted with paracetamol poisoning were studied and concomitant drug intake was recorded. The relative risk of hepatic encephalopathy, death or liver transplantation, hepatic dysfunction, liver cell damage, and renal dysfunction associated with concomitant overdosing of other drugs was evaluated by multivariate analysis. Concomitant drug overdose was found in 207 patients (31%, 95% confidence interval [CI] 27, 34%). Concomitant overdosing of benzodiazepines (99 cases), opioid analgesics (38 cases), acetylsalicylic acid (33 cases), and NSAID (32 cases) predominated. Concomitant benzodiazepine overdose was an independent risk factor in the development of hepatic encephalopathy (odds ratio [OR] 1.91; CI 1.00, 3.65) and renal dysfunction (OR 1.81; CI 1.00, 3.22). Concomitant overdosing of opioid analgesics was a protective factor in the development of hepatic encephalopathy (OR 0.26; CI 0.07, 0.96). Concomitant acetylsalicylic acid overdose was a risk factor in the development of hepatic encephalopathy (OR 4.87; CI 1.52, 15.7) and death or liver transplantation (OR 6.04; CI 1.69, 21.6). A tendency towards a more favourable outcome was observed in patients with concomitant NSAID overdose. Concomitant overdosing of benzodiazepines or analgesics is frequent in patients admitted with paracetamol poisoning. Concomitant benzodiazepine or acetylsalicylic acid overdose was associated with more severe toxicity, whereas concomitant overdosing of opioid analgesics was associated with less toxicity.

Healing of Nonsteroidal Anti-inflammatory Drug-Associated Ulcers and Erosions, and Relief of Dyspeptic Symptoms: A Commentary on the New Data

Anumber of treatments are available for promoting the healing of gastric and duodenal ulcers associated with the ingestion of nonsteroidal anti-inflammatory drugs). These include the proton pump inhibitors and H2-receptor antagonists, which inhibit gastric acid secretion, and prostaglandin analogs, which suppress gastric acid and are also cytoprotective. A key issue, however, is what represents optimal therapy in peptic ulcer patients who must continue NSAID treatment. To date, the H2-receptor antagonists have been the most extensively studied therapeutic class in this disease area, but the data are conflicting. In a multicenter study by Lancaster-Smith et al, healing of NSAID-associated ulcers with ranitidine, 150 mg twice daily, was significantly lower in patients who continued their NSAID therapy when compared with those who stopped. At 8 weeks, gastric ulcers had healed in 63% of patients who continued NSAID therapy, compared with 95% who stopped. In duodenal ulcer, the 8-week healing rates were 84% in patients who continued NSAID therapy and 100% in those who stopped. In contrast, however, other studies have not shown such an effect of continued NSAID ingestion on ranitidine therapy. In a group of 67 patients, Manniche et al reported similar healing rates with either ranitidine, 150 mg twice daily, or sucralfate, 1 g four times daily, irrespective of whether NSAID therapy was discontinued. Similarly, in a separate study of 149 arthritic patients, the 4-week healing rates with ranitidine, 150 mg twice daily, in patients who continued or discontinued NSAID therapy were 67% and 68%, respectively, for gastric ulcer and 61% and 81%, respectively, for duodenal ulcer. In the same study, the 4-week healing rates in patients treated with placebo who discontinued NSAID therapy were 47% and 42% for gastric and duodenal ulcer, respectively. While prophylaxis of NSAID-associated gastroduodenal ulcers with the prostaglandin analog misoprostol is well documented, data are very limited on its acute use for healing, particularly in patients who continue to take NSAID therapy. Misoprostol, 200 mg four times daily, has been compared with placebo in a double-blind trial involving 77 patients with endoscopically verified gastric ulcer. In this study, the healing rate at 8 weeks was 90% with placebo. Thus, the cumulative healing rate with misoprostol was not better than with placebo at 8 weeks, although it was significantly higher at 4 weeks, possibly suggesting that misoprostol accelerates the healing of gastric ulcers. NSAID therapy was discontinued during this study, however. The efficacy of the proton pump inhibitor omeprazole is well established in the acute management of peptic ulcer disease, but there are only limited data for NSAIDassociated gastroduodenal ulcers. In a double-blind study by Walan et al, omeprazole, 20 mg once daily, was found to be superior to ranitidine, 150 mg twice daily, in healing gastric ulcers, including a subgroup of patients taking concomitant NSAID therapy. The overall healing rate with omeprazole was 69% after 4 weeks, and similarly, was 61% in the subgroup of patients who received concomitant NSAID therapy. In comparison, the overall 4-week healing rate with ranitidine was 59%, but only 32% in patients who were taking NSAIDs. This study suggested that gastric ulcer healing with ranitidine, but not omeprazole, was affected by concomitant NSAID ingestion; however, there were only 68 patients in the subgroup taking NSAIDs. Furthermore, Lauritsen et al have reported, in a double-blind study, that the healing of duodenal ulcers in NSAID users is similar with omeprazole, 20 and 40 mg once daily. In summary, there has been a lack of comparative studies of any size between potentially active drugs, particularly involving patients who need to continue NSAID therapy. The two new, large, randomized, double-blind, multicenter, controlled studies—Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-Associated Ulcer Treatment (ASTRONAUT) and Omeprazole versus Misoprostol of NSAID-Induced Ulcer Management (OMNIUM)—involved almost 1,500 patients who continued to take daily NSAID therapy. They have provided new comparative data on the efficacy and tolerability of original magnification, 20 and 40 mg once daily, ranitidine, 150 mg twice daily, and misoprostol, 200 mg four times daiFrom the Department of Medicine, University of Sydney, The Nepean Hospital, Penrith, New South Wales, Australia. Requests for reprints should be addressed to Nicholas J. Talley, MD, PhD, Division of Medicine, The Nepean Hospital, P.O. Box 63, Penrith, New South Wales 2751, Australia.

Risk Factors, Co-Medication, and Concomitant Diseases: Their Influence on the Outcome of Therapy with Cisapride: General Discussion

In a 28-day non-blinded study of 1071 patients with functional dyspeptic symptoms in a general practice setting, 666 presented with mainly typical symptoms of functional dyspepsia and received 5 mg cisapride three times daily, while 405 with predominating symptoms indicative of gastroesophageal reflux received 10 mg cisapride three times daily. On the basis of an anamnestic risk factor analysis for organic lesions, 'low-risk' patients were to be treated directly with cisapride, while for 'high-risk' patients a more thorough gastrointestinal examination was recommended before starting cisapride. Of patients in the dyspepsia group 75% reported a good or excellent response; the corresponding rate was 80% in the reflux group. Low-risk patients in both groups tended to respond better than high-risk patients (mean difference, 11%). Patients and investigators reached identical assessments of response. Concomitant antacids, calcium antagonists, beta-blockers and sedatives did not affect the results, but concomitant NSAIDs reduced the mean improvement rate by 14% (p < 0.01). Adverse effects such as abdominal cramps and loose stools were uncommon (< or = 3.4%).