Cardiovascular safety of lumiracoxib: A meta-analysis of all randomized controlled trials ≥1 week and up to 1 year in duration of patients with osteoarthritis and rheumatoid arthritis

Matchaba, Patrice; Gitton, Xavier; Krammer, Gerhard; Ehrsam, Elena; Sloan, Victor S.; Olson, Mark W.; Mellein, B.; Hoexter, Godehard; Orloff, John J.; Garaud, Jean–Jacques

doi:10.1016/j.clinthera.2005.07.019

Cited by 53 publications

(32 citation statements)

References 27 publications

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“…It also does not have the high COX-2 selectivity of etoricoxib or rofecoxib. Novartis embarked on large scale studies to determine the CV safety with lumiracoxib which was compared with ibuprofen and naproxen all at prescription level dosages Matchaba et al 2005;Farkouh et al 2009) (see Tables 30, 31).…”

Section: Serious CV Conditionsmentioning

confidence: 99%

Ibuprofen: pharmacology, efficacy and safety

2009

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This assessment of the safety and benefits of ibuprofen can be summarized thus: (1) Ibuprofen at OTC doses has low possibilities of serious GI events, and little prospect of developing renal and associated CV events. Ibuprofen OTC does not represent a risk for developing liver injury especially the irreversible liver damage observed with paracetamol and the occasional liver reactions from aspirin. (2) The pharmacokinetic properties of ibuprofen, especially the short plasma half-life of elimination, lack of development of pathologically related metabolites (e.g. covalent modification of liver proteins by the quinine-imine metabolite of paracetamol or irreversible acetylation of biomolecules by aspirin) are support for the view that these pharmacokinetic and notably metabolic effects of ibuprofen favour its low toxic potential. (3) The multiple actions of ibuprofen in controlling inflammation combine with moderate inhibition of COX-1 and COX-2 and low residence time of the drug in the body may account for the low GI, CV and renal risks from ibuprofen, especially at OTC doses.

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Section: Serious CV Conditionsmentioning

confidence: 99%

Ibuprofen: pharmacology, efficacy and safety

2009

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“…treatment found no evidence of increase in cardiovascular risk compared with naproxen, placebo or all comparators. 87 With the recent findings of the cardiovascular adverse effects of the COX-2 inhibitors, a potential safety concern has been raised as to whether the increased cardiovascular events would be a class effect for all NSAIDs. Unfortunately, there are no placebo-controlled RCTs addressing the cardiovascular safety of tNSAIDs, only observational studies, information from basic and human pharmacology, and the previously discussed tNSAID comparator RCTs.…”

Section: Meta-analysis Of Rcts 84mentioning

confidence: 99%

An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs

Ong¹,

Lirk²,

Tan³

et al. 2007

Clinical Medicine & Research

491

286

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Nonsteroidal anti-inflammatory drugs (NSAIDs), including both traditional nonselective NSAIDs and the selective cyclooxygenase (COX)-2 inhibitors, are widely used for their anti-inflammatory and analgesic effects. NSAIDs are a necessary choice in pain management because of the integrated role of the COX pathway in the generation of inflammation and in the biochemical recognition of pain. This group of drugs has recently come under scrutiny because of recent focus in the literature on the various adverse effects that can occur when applying NSAIDs.This review will provide an educational update on the current evidence of the efficacy and adverse effects of NSAIDs. It aims to answer the following questions: (1) are there clinically important differences in the efficacy and safety between the different NSAIDs, (2) if there are differences, which are the ones that are more effective and associated with fewer adverse effects, and (3) which are the effective therapeutic approaches that could reduce the adverse effects of NSAIDs. Finally, an algorithm is proposed which delineates a general decision-making tree to select the most appropriate analgesic for an individual patient based on the evidence reviewed. Keywords: Analgesics; COX-2 specific inhibitors; NSAIDs; Pain Nonst eroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications in the world because of their demonstrated efficacy in reducing pain and inflammation. 1 Their efficacy has been documented in a number of clinical disorders, including osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, gout, dysmenorrhea, dental pain and headache. [2][3][4][5][6][7][8] The basic mode of action is inhibition of the pro-inflammatory enzyme cyclooxygenase (COX). NSAIDs as a class comprise both traditional nonselective NSAIDs (tNSAIDs) that nonspecifically inhibit both COX-1 and COX-2, and selective COX-2 inhibitors. Although effective at relieving pain and inflammation, tNSAIDs are associated with a significant risk of serious gastrointestinal adverse events with chronic use. 9 Therefore, specific inhibitors of the COX-2 isoenzyme were developed, thus opening the possibility to provide antiinflammatory and analgesic benefits, while theoretically leaving the gastroprotective activity of the COX-1 isoenzyme intact. However, important concerns have recently been raised regarding the potential cardiovascular toxicity of COX-2 inhibitors. 10This review will provide an educational update of the scientific evidence for the efficacy and adverse effects of NSAIDs in view of the emerging new information for this class of drugs. It is composed deliberately to be a classic, pragmatic review and draws on the results of published systematic reviews and studies regarding the topic. It aims to answer the following questions: (1) are there clinically important differences in the efficacy and safety between the different NSAIDs, (2) if there are differences, which are the ones that are more effective and associated with fewer adverse effects, and (3) which are...

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“…Senere har verken Kearney og medarbeidere (22) eller McGettigan & Henry (3) funnet holdepunkter for kardioprotektive effekter ved bruk av naproksen. Andre analyser kan på den annen side tyde på at naproksen har en viss kardioprotektiv effekt (23,24).…”

Section: Naproksenunclassified