Trends in Prescribing of Non-steroidal Anti-inflammatory Medications in the US Ambulatory Care Setting From 2006 to 2016

Keshwani, Shailina; Smith, Steven M.; Brown, Joshua D.; Lo‐Ciganic, Wei‐Hsuan; Yang, Seonkyeong; Smolinski, Nicole E; Hincapie-Castillo, Juan M.

doi:10.1016/j.jpain.2023.06.008

Cited by 3 publications

(3 citation statements)

References 32 publications

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“…Optimizing NSAID therapy is one strategy to address the current opioid crisis, 2 and rates of NSAID use have increased in recent years as opioid prescriptions have declined. 9 Although they lack the addictive potential of opioids, NSAIDs have the potential to cause serious, and in some cases, life-threatening adverse events, including gastrointestinal bleeding, renal dysfunction, hypertension, and thrombotic cardiovascular events. 10 Undetected blood pressure (BP) increases that may impact cardiovascular morbidity and mortality at the population level are a particular concern.…”

Section: Introductionmentioning

confidence: 99%

Degree of Cyclooxygenase-2 Inhibition Modulates Blood Pressure Response to Celecoxib and Naproxen

Theken,

Ghosh,

Skarke

et al. 2024

Preprint

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BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of adverse cardiovascular events via suppression of cyclooxygenase (COX)-2-derived prostacyclin (PGI2) formation in heart, vasculature, and kidney. The Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen (PRECISION) trial and other large clinical studies compared the cardiovascular risk of traditional NSAIDs (i.e. naproxen), which inhibit both COX isozymes, with NSAIDs selective for COX-2 (i.e. celecoxib). However, whether pharmacologically equipotent doses were used - that is, whether a similar degree of COX-2 inhibition was achieved - was not considered. We compared drug target inhibition and blood pressure response to celecoxib at the dose used by most patients in PRECISION with the lowest recommended naproxen dose for osteoarthritis, which is lower than the dose used in PRECISION.MethodsSixteen healthy participants (19-61 years) were treated with celecoxib (100 mg every 12h), naproxen (250 mg every 12h), or placebo administered twice daily for seven days in a double-blind, crossover design randomized by order. On Day 7 when drug levels had reached steady state, the degree of COX inhibition was assessedex vivoandin vivo. Ambulatory blood pressure was measured throughout the final 12h dosing interval.ResultsBoth NSAIDs inhibited COX-2 activity relative to placebo, but naproxen inhibited COX-2 activity to a greater degree (62.9±21.7%) than celecoxib (35.7±25.2%; p<0.05). Similarly, naproxen treatment inhibited PGI2formationin vivo(48.0±24.9%) to a greater degree than celecoxib (26.7±24.6%; p<0.05). Naproxen significantly increased blood pressure compared to celecoxib (differences in least-square means of mean arterial pressure: 2.5 mm Hg (95% CI: 1.5, 3.5); systolic blood pressure: 4.0 mm Hg (95% CI: 2.9, 5.1); diastolic blood pressure: 1.8 mm Hg (95% CI: 0.8, 2.8); p<0.05 for all). The difference in systolic blood pressure relative to placebo was associated with the degree of COX-2 inhibition (p<0.05).ConclusionsCelecoxib 200 mg/day inhibited COX-2 activity to a lesser degree than naproxen 500 mg/day, resulting in a less pronounced blood pressure increase. While the PRECISION trial concluded the non-inferiority of celecoxib regarding cardiovascular risk, this is based on a comparison of doses that are not equipotent.ClinicalTrials.govidentifier:NCT02502006(https://clinicaltrials.gov/study/NCT02502006)Clinical PerspectiveNaproxen 250 mg twice a day inhibited COX-2 activity to a greater degree than celecoxib 100 mg twice a day.The degree of COX-2 inhibition was associated with the increase in systolic blood pressure with NSAID treatment relative to placebo.Dose and its pharmacological potency achievedin vivoshould be considered when evaluating the relative cardiovascular safety of COX-2-selective vs. non-selective NSAIDs.

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Section: Introductionmentioning

confidence: 99%

Degree of Cyclooxygenase-2 Inhibition Modulates Blood Pressure Response to Celecoxib and Naproxen

Theken,

Ghosh,

Skarke

et al. 2024

Preprint

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“…3 NSAIDs are available in prescription and over-the-counter (OTC) strengths, a variety of different formulations, and oral (most common), intravenous, injectable and topical forms. The use of NSAIDs has risen globally throughout the last 20 years, [4][5][6][7][8] in part due to increasing rates of chronic and persistent pain and an increasing ageing population.…”

Section: Introductionmentioning

confidence: 99%

Scoping review of interventions to de-implement potentially harmful non-steroidal anti-inflammatory drugs (NSAIDs) in healthcare settings

Rockwell,

Oyese,

Singh

et al. 2024

BMJ Open

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ObjectivesPotentially harmful non-steroidal anti-inflammatory drugs (NSAIDs) utilisation persists at undesirable rates worldwide. The purpose of this paper is to review the literature on interventions to de-implement potentially harmful NSAIDs in healthcare settings and to suggest directions for future research.DesignScoping review.Data sourcesPubMed, CINAHL, Embase, Cochrane Central and Google Scholar (1 January 2000 to 31 May 2022).Study selectionStudies reporting on the effectiveness of interventions to systematically reduce potentially harmful NSAID utilisation in healthcare settings.Data extractionUsing Covidence systematic review software, we extracted study and intervention characteristics, including the effectiveness of interventions in reducing NSAID utilisation.ResultsFrom 7818 articles initially identified, 68 were included in the review. Most studies took place in European countries (45.6%) or the USA (35.3%), with randomised controlled trial as the most common design (55.9%). Interventions were largely clinician-facing (76.2%) and delivered in primary care (60.2%) but were rarely (14.9%) guided by an implementation model, framework or theory. Academic detailing, clinical decision support or electronic medical record interventions, performance reports and pharmacist review were frequent approaches employed. NSAID use was most commonly classified as potentially harmful based on patients’ age (55.8%), history of gastrointestinal disorders (47.1%), or history of kidney disease (38.2%). Only 7.4% of interventions focused on over-the-counter (OTC) NSAIDs in addition to prescription. The majority of studies (76.2%) reported a reduction in the utilisation of potentially harmful NSAIDs. Few studies (5.9%) evaluated pain or quality of life following NSAIDs discontinuation.ConclusionMany varied interventions to de-implement potentially harmful NSAIDs have been applied in healthcare settings worldwide. Based on these findings and identified knowledge gaps, further efforts to comprehensively evaluate the effectiveness of interventions and the combination of intervention characteristics associated with effective de-implementation are needed. In addition, future work should be guided by de-implementation theory, focus on OTC NSAIDs and incorporate patient-focused strategies and outcomes, including the evaluation of unintended consequences of the intervention.

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“…3 NSAIDs are available in prescription and over-the-counter (OTC) strengths, a variety of different formulations, and oral (most common), intravenous, injectable, and topical forms. The use of NSAIDs has risen globally throughout the last twenty years, [4][5][6][7][8] in part due to increasing rates of chronic and persistent pain and an increasing aging population.…”

Section: Introductionmentioning

confidence: 99%

A Scoping Review of Interventions to De-implement Potentially Harmful Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in Healthcare Settings

Rockwell,

Oyese,

Singh

et al. 2023

Preprint

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Objectives: Potentially harmful nonsteroidal anti-inflammatory drugs (NSAIDs) utilization persists at undesirable rates throughout the world. The purpose of this paper is to review the literature on interventions to de-implement potentially harmful NSAIDs in healthcare settings and to suggest directions for future research. Design: Scoping review Data Sources: PubMed, CINAHL, Embase, Cochrane Central, and Google Scholar (2000-2022). Study Selection: Studies reporting on the effectiveness of interventions to systematically reduce potentially harmful NSAID utilization in healthcare settings. Data Extraction: Using Covidence systematic review software, we extracted study and intervention characteristics, including the effectiveness of interventions in reducing NSAID utilization. Results: From 7,818 articles initially identified, 68 were included in the review. Most studies took place in European countries (45.6%) or the U.S. (35.3%), with randomized controlled trial as the most common design (55.9%). The majority of studies (76.2%) reported a reduction in the utilization of potentially harmful NSAIDs. Interventions were largely clinician-facing (76.2%) and delivered in primary care (60.2%). Academic detailing, clinical decision support or electronic medical record interventions, performance reports, and pharmacist review were frequent approaches employed. NSAID use was most commonly classified as potentially harmful based on patients age (55.8%) or history of gastrointestinal disorders (47.1%) or kidney disease (38.2%). Only 7.4% of interventions focused on over-the-counter NSAIDs in addition to prescription. Few studies (5.9%) evaluated pain or quality of life following NSAIDs discontinuation. Conclusion: Many varied interventions are effective in de-implementing potentially harmful NSAIDs in healthcare settings. Efforts to adapt, scale, and disseminate these interventions are needed. In addition, future interventions should address over-the-counter NSAIDs, which are broadly available and widely used. Evaluating unintended consequences of interventions, including patient-focused outcomes, is another important priority.

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Trends in Prescribing of Non-steroidal Anti-inflammatory Medications in the US Ambulatory Care Setting From 2006 to 2016

Cited by 3 publications

References 32 publications

Degree of Cyclooxygenase-2 Inhibition Modulates Blood Pressure Response to Celecoxib and Naproxen

Degree of Cyclooxygenase-2 Inhibition Modulates Blood Pressure Response to Celecoxib and Naproxen

Scoping review of interventions to de-implement potentially harmful non-steroidal anti-inflammatory drugs (NSAIDs) in healthcare settings

A Scoping Review of Interventions to De-implement Potentially Harmful Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in Healthcare Settings

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