Cardiovascular safety of non-steroidal anti-inflammatory drugs

British Medical Journal  2011; 342:c7086 (Published 11 January 2011)

Implications and conclusions

The observation that cardiovascular risk is not clearly associated with specificity of cyclo-oxygenase-2 inhibitors implies that no prediction of cardiovascular risk can be made based on such specificity. Therefore the use of other non-steroidal anti-inflammatory drugs not covered by our analysis should be reconsidered, as well as the over the counter availability of non-steroidal anti-inflammatory drugs such as diclofenac or ibuprofen. In general, naproxen seems to be the safest analgesic for patients with osteoarthritis in cardiovascular terms but this advantage has to be weighed against gastrointestinal toxicity and the need for concomitant prescription of a proton pump inhibitor in many patients. In the light of the results of one study,28 celecoxib 400 mg prescribed once daily may be considered as an alternative option. Other alternatives include paracetamol and opioids. Compared with placebo, however, paracetamol results in only a small reduction in pain and may be associated with clinically relevant hepatotoxicity, even in dosages recommended for musculoskeletal pain.42 43 The analgesic effect of opioids is somewhat more pronounced but outweighed by large increases in the risk of adverse events.44 In conclusion, the options for the treatment of chronic musculoskeletal pain are limited and patients and clinicians need to be aware that cardiovascular risk needs to be taken into account when prescribing.

http://www.bmj.com/content/342/bmj.c7086.full?sid=c139b292-30b1-4c80-825c-f4c9874ad5b1

Duloxetine Shows Promise in Aromatase Inhibitor-Associated Musculoskeletal Syndrome

By Jill Stein SAN ANTONIO, Tex -- December 13, 2010 -- The serotonin and norepinephrine reuptake inhibitor duloxetine seems to be effective and well tolerated in women with hormone receptor-positive, early-stage breast cancer treated with an aromatase inhibitor (AI), according to a study presented here at the 33rd annual San Antonio Breast Cancer Symposium (SABCS). Norah L. Henry, MD, University of Michigan, Ann Arbor, Michigan, and colleagues tested the use of duloxetine in postmenopausal women with breast cancer who developed new or worsening grade 1 or higher musculoskeletal pain or sensory neuropathy after receiving adjuvant AI therapy for at least 2 weeks. Treatment for AI-associated musculoskeletal symptoms is often ineffective, Dr. Henry pointed out on December 11. AI-associated musculoskeletal syndrome occurs in roughly half of treated patients. Duloxetine was selected for evaluation because the agent has been effective in the treatment of multiple chronic pain states, including fibromyalgia, osteoarthritis, and low-back pain. The drug may act via alteration of central pain processing. In the trial, women received duloxetine 60 mg daily and had the option of increasing their dose to 60 mg twice daily for a total of 8 weeks. The primary endpoint was a 30% decrease in average pain score over 8 weeks. Results showed that 21 (72.4%) of 29 patients achieved at least a 30% decrease in average pain, and 18 (78.3%) of 23 patients who completed protocol-directed treatment continued duloxetine therapy. Duloxetine therapy reduced pain severity by a mean of 60%, which is comparable to the response rates for other chronic pain conditions, Dr. Henry said. Treatment also improved functional status and depression. Overall, 20.6% of patients stopped therapy prematurely because of side effects. Dr. Henry said that the study findings are limited by the small sample size, "fairly high" discontinuation rate, and lack of a concurrent control group. [Presentation title: Duloxetine for Treatment of Aromatase Inhibitor-Associated Musculoskeletal Syndrome (AIMSS). Abstract PD-08-06] http://www.docguide.com/news/content.nsf/news/852576140048867C852577F80072A223