Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis

Abstract

Objective To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs.Design Network meta-analysis.Data sources Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data.Study selection All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility.Data extraction The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data.Data synthesis 31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death.Conclusions Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.

Pre-existent Asymmetry in the Human Cyclooxygenase-2 Sequence Homodimer

“…Celecoxib was from physician samples of Celebrex R . [1-14 C]AA (1.85 GBq/mmol) and [acetyl- 14 C]acetylsalicylic acid (1.85 GBq/mmol) were from American Radiolabeled Chemicals. Hexane, isopropyl alcohol, and acetic acid were HPLC grade from Thermo Fisher Scientific, Inc. Anti-PGHS-2 antibodies directed against the 18-amino acid insert unique to PGHS-2 were as described (26).…”

“…The gel was washed and stained with Coomassie Blue for 1 h and then exposed to a storage phosphor screen (GE Healthcare) for 24 h. The screen was imaged using photo-stimulatable storage phosphorimage acquisition at 200 m with a Typhoon Trioϩ Variable Mode Imager (Amersham Biosciences). The percentages of 14 C-acetylated huPGHS-2 glycoforms with molecular masses estimated to be 70 or 72 kDa were quantified using ImageJ software. Anti-FLAG or anti-PGHS-2 antibodies were used to quantify huPGHS-2 variants by Western transfer blotting as described previously (17).…”

“It looks after me”: How older patients make decisions about analgesics for osteoarthritis

“…However, whereas paracetamol at maximum dose (4 g/day) is relatively safe, NSAIDs (both nonselective and COX-2 selective agents) have a range of serious adverse effects, particularly affecting those aged 65 and above. These include gastrointestinal ulceration, myocardial infarction, stroke, hypertension, renal impairment and cardiac failure (4)(5)(6). Among patients over the age of 65, non-aspirin NSAID-related peptic ulcer disease contributes to a considerable number of hospitalizations each year (7).…”

Fast determination of naproxen in pharmaceutical formulations by batch injection analysis with pulsed amperometric detection

“…However, a recent study classified naproxen as the least harmful NSAID in cardiovascular terms. 3 Different analytical methods have been proposed for the determination of naproxen in pharmaceutical formulations including spectrophotometry (UV region), 4,5 spectrofluorimetry, [6][7][8] capillary isotachophoresis 9 and high-performance liquid-chromatography (HPLC) coupled with spectrophotometric, 10 amperometric 11 and mass spectrometric detectors. 1 Nevertheless, these analytical methods require expensive equipment and reagents, are time-consuming and often necessitate laborious pre-and post-column derivatization procedures.…”