Trends of non-union and prescriptions for non-steroidal anti-inflammatory drugs in the United States, 1993-2012.

BACKGROUND AND PURPOSE: Surgical care and pain management for patients with fractures have evolved over the years. We wanted to ascertain if there were any changes in the incidence of non-unions and, if so, whether the use of non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 selective inhibitors, might have an effect. PATIENTS AND METHODS: We used the National Inpatient Sample (NIS) to estimate the annual number of patients hospitalized for surgical treatment of a non-union between 1993 and 2012, and calculated age-adjusted rates of non-union. We estimated the prevalence of prescriptions for NSAIDs from 1996 through 2012 using the Medical Expenditure Panel Survey (MEPS). The interrupted time-series analysis was used to relate quarterly rates of non-union to changes in prescriptions for NSAIDs between 1996 and 2009. RESULTS: The annual estimate of non-unions in the USA declined 30% from 25,634 in 1993 to 17,815 in 2012 (p < 0.001). Specifically, the age-adjusted rate of non-unions decreased by 44% from 8.6 per 10(5) persons in 1996 to 4.8 per 10(5) persons in 2012 (p < 0.001). However, there was an 8% increase in the incidence rate of non-unions (p = 0.003) between 2000 and 2004, when certain COX-2 selective inhibitors were on the market and their prescriptions were prevalent at around 6% among those with fractures. A drop in non-union estimates from 22,321 in 2010 to 18,789 in 2011 (p = 0.04) also coincided with a marked decrease in prescriptions for NSAIDs in patients with fractures, from 22% to 14% (p = 0.02). INTERPRETATION: Non-unions in the USA declined substantially between 1993 and 2012, but this was interrupted by changes in prescriptions for NSAIDs, with sustained increases between 2000 and 2004 followed by transient decreases in 2005 and 2011.

What happened to the prescribing of other COX-2 inhibitors, paracetamol and non-steroidal anti-inflammatory drugs when rofecoxib was withdrawn in Australia?

OBJECTIVES: To analyse how the prescribing of cyclooxygenase-2 (COX-2) inhibitors, non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs) and paracetamol (acetaminophen) changed when rofecoxib was withdrawn in 2004. METHOD: COX-2 inhibitors, paracetamol and ns-NSAID's use was measured using dispensing data for concession beneficiaries subsidized by the Australian Pharmaceutical Benefit Scheme (PBS) for the period of 1997-2005. Data were downloaded from the Medicare Australia website and converted, according to the World Health Organization (WHO) Anatomical Therapeutic Chemical (ATC)/Defined Daily Dose (DDD) (2005), to DDD/1000 concession beneficiaries/day. RESULTS: In the period 2000-2004, the use of COX-2 inhibitors was progressively increased. Overall NSAID's use changed from approximately 80 to 105 DDD/1000 concession beneficiaries/day while a decrease of ns-NSAIDs from about 70 to 40 DDD/1000 concession beneficiaries/day was observed. Following rofecoxib withdrawal, the overall NSAIDs use declined. In 2005, celecoxib prescription declined (23%) while prescription of meloxicam increased by 62%. Use of paracetamol was steady over the period 1997-2004 (around 40 DDD/1000 concession beneficiaries/day). In April 2005, a slight increase in paracetamol use was observed. CONCLUSION: Our analysis showed that COX-2 inhibitors prescribing markedly influenced the overall NSAIDs prescribing in Australia. When COX-2 inhibitors were introduced their uptake was rapid and extensive. Following rofecoxib withdrawal, the total overall dispensing of NSAIDs returned to a similar value as before COX-2 inhibitors' introduction. The decrease was due both to rofecoxib withdrawal and to a reduction in celecoxib prescribing. However, meloxicam use increased. Paracetamol prescribing was steady, between 1997 and 2005 and was not affected when the COX-2 inhibitors were introduced on to the market and after rofecoxib withdrawal, rather than increasing as might have been anticipated after rofecoxib withdrawal.

Characterizing new users of NSAIDs before and after rofecoxib withdrawal.

AIMS: To characterize patients initiated on nonsteroidal anti-inflammatory drugs (NSAIDs), pre and postrofecoxib withdrawal, by age, gender and concomitant cardiovascular (CV) therapy. METHODS: A national primary care prescription database was used to identify patients who initiated NSAID therapy pre and postrofecoxib withdrawal. Patients receiving CV therapy were identified in the same periods also. Adjusted odds ratios (OR) and 95% confidence intervals are presented. RESULTS: Female patients [OR = 1.15 (1.11, 1.19)], those over 65 years [OR = 2.76 (2.65, 2.86)] and those at CV risk [OR = 1.72 (1.67, 1.79)] were more likely to start on celecoxib (over a nonselective NSAID) than male patients, those under 65 years and those not at CV risk. Similar results were found for rofecoxib and nimesulide. Post-withdrawal analysis showed results comparable to the pre-withdrawal period. CONCLUSION: The results highlight a possible uncertainty experienced by prescribers of treatment alternatives available and a lack of unbiased information at this time for at-risk groups.

The effect of the withdrawal of rofecoxib on prescribing patterns of COX-2 inhibitors in Scotland.

BACKGROUND: Concerns have been raised regarding the cardiovascular safety of the COX-2 inhibitors. In September 2004, rofecoxib was withdrawn from the market as a result of concerns regarding its cardiovascular safety. AIMS & METHODS: We set out to examine the effect of the withdrawal of rofecoxib on the prescription of other COX-2 inhibitors and nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) in Scotland, using a national prescription database. RESULTS: The withdrawal of rofecoxib led to an initial increase in the prescription of celecoxib as prescribers presumably switched to this alternative agent. However, this rise was short-lived, presumably as a result of concerns that the safety concerning rofecoxib may be a class effect. A parallel increase in the prescription of diclofenac and ibuprofen was also noted, suggesting that prescribers were prescribing these medications as alternatives to COX-2 inhibitors. CONCLUSIONS: While prescribers and their patients may have initially interpreted safety concerns regarding rofecoxib to be drug specific, prescribers appear to have interpreted this effect to be class specific.

The role of COX-2 inhibitors in the perioperative setting: efficacy and safety--a systematic review.

A new class of nonsteroidal anti-inflammatory drugs (NSAIDs) selective for cyclooxygenase-2 (COX-2) offers new options for managing perioperative pain. However, new and conflicting data have emerged regarding all nonsteroidal anti-inflammatory drugs, including those selective for COX-2. The data highlight the potential for increased risks of adverse cardiovascular events associated with all NSAIDs and of potential serious skin reactions and gastrointestinal bleeding with specific agents. As of June 2005, the National Institutes of Health and Food and Drug Administration suspended all clinical trials involving NSAIDs. This article reviews 30 prospective studies on the role of COX-2 selective inhibitors in the perioperative setting. The studies examined a variety of variables, including efficacy, perioperative opioid reduction, and effects on platelet aggregation and renal function. The data reveal an overall reduction in postoperative opioid use and significant patient satisfaction with perioperative COX-2 use, no effect on platelet aggregation, and a minor negative effect on renal function. The literature suggests that perioperative use of selective COX-2 inhibitors can be well tolerated and efficacious in carefully selected patient groups. Further data are needed to fully examine the role of these drugs in the perioperative setting. Intensive research into cardiovascular issues surrounding all NSAIDs is warranted.