Trends and Disparities in High-Risk Nonsteroidal Anti-Inflammatory Drug Utilization

ABSTRACT

Objectives: Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) poses a risk to patients with chronic kidney disease (CKD), heart failure (HF), and hypertension (HTN). We evaluated changes in NSAID utilization among a large cohort of Virginia patients with CKD, HF, and/or HTN during the COVID-19 pandemic and assessed variation by patient demographic characteristics.

Study Design: Quasi-experimental difference-in-differences approach.

Methods: Using claims from the Virginia All-Payer Claims Database, we identified NSAID prescriptions dispensed to patients with CKD, HF, and/or HTN during the years 2019-2021. We applied Poisson regression to assess the impact of the COVID-19 pandemic (March 1, 2020- December 31, 2021) on NSAID utilization rates, stratifying incidence rate ratios (IRRs) by rurality, sex, and age.

Results: Extrapolated to the statewide population, approximately 3.8 million NSAID prescriptions were dispensed to Virginians with CKD, HF, and/or HTN between 2019 and 2021. Utilization rates declined by 23% during the first 2 years of the pandemic, were greater in rural vs urban areas (IRR, 1.594; 95% CI, 1.408-1.803) and among those aged 40 to 64 years, 65 to 79 years, and 80 years and older vs those aged 18 to 39 years (40-64 years: IRR, 6.366; 95% CI, 5.979-6.778; 65-79 years: IRR, 6.980; 95% CI, 6.568-7.417; ≥ 80 years: IRR, 5.223; 95% CI, 4.772-5.715); and were lower among men than women (IRR, 0.779; 95% CI, 0.758-0.800). The pandemic impacted rural and urban areas and women and men similarly but was associated with lower NSAID utilization among the 3 older age groups vs those aged 18 to 39 years (40-64 years: IRR, 0.869; 95% CI, 0.812-0.931; 65-79 years: IRR, 0.788; 95% CI, 0.733-0.847; ≥ 80 years: IRR, 0.769; 95% CI, 0.709-0.833).

Conclusions: Despite a modest decline during the first 2 years of the pandemic, NSAID use remains prevalent among patients with CKD, HF, and/or HTN, especially in rural areas and among women. Results highlight the need for tailored deprescribing efforts.

Am J Manag Care. 2026;32(8):464-468.

doi:10.37765/ajmc.2026.90002

Takeaway Points

• Although utilization rates decreased during the COVID-19 pandemic, an estimated 3.8 million high-risk nonsteroidal anti-inflammatory drug (NSAID) prescriptions were dispensed to Virginia patients with chronic kidney disease, heart failure, and/or hypertension between 2019 and 2021.
• Previous research shows higher rates of inappropriate opioid utilization in rural vs urban areas. This study identified similar disparities in high-risk NSAID use (59.4% higher in rural vs urban areas).
• High-risk NSAID use was also significantly higher among women than men.
• Results highlight the need for tailored deprescribing efforts.

More than 55 million Americans (25% of the adult population) experience chronic pain,¹ but the burden of chronic pain is not evenly distributed across the population. For example, individuals living in rural areas experience significantly higher rates of chronic pain than those living in urban areas.² Multiple social and structural factors contribute to this disparity, including the greater likelihood for rural residents to hold manual labor jobs, encounter financial barriers to care, and experience limited access to pain management specialists and nonpharmacological pain therapies.^3,4 A recent scoping review reports higher rates of low-value care (health services that offer no clinical benefit and have the potential to cause harm) for chronic musculoskeletal pain in rural vs urban areas.⁵ Although this review identified disparate utilization of some low-value/high-risk medications (eg, opioids) in rural areas, no studies focused on nonsteroidal anti-inflammatory drugs (NSAIDs), which are among the most common treatments for chronic pain.

Although NSAIDs are effective for reducing pain and inflammation in some chronic pain scenarios, they pose potential harm to certain individuals. The National Kidney Foundation, American Heart Association, American Geriatrics Society, and others recommend limiting or avoiding long-term use of NSAIDs in most patients with chronic kidney disease (CKD), heart failure (HF), and hypertension (HTN) due to the risk of adverse events.^6-9 Despite these recommendations, NSAID use among patients with CKD, HF, and/or HTN (ie, high-risk use) has persisted. In their 2020 systematic review, Lefebvre et al identified high-risk NSAID use in up to 20% of patients with CKD.¹⁰ Similar utilization rates have been reported among patients with HF and HTN.^11,12 It is unclear whether and how high-risk NSAID utilization among patients with CKD, HF, and/or HTN has changed in more recent years.

The COVID-19 pandemic, declared by the World Health Organization in March 2020, profoundly influenced health care delivery in the US. Use of many prescription medications decreased early in the pandemic but generally rebounded to near or higher than prepandemic rates by the end of 2021.^13,14 Similar trends have been reported for low-value health services.^15-17 Levine et al observed a substantial reduction in low-value/high-risk NSAID utilization among adults insured by Medicare and commercial payers during the first 3 months of the pandemic.¹⁸ Understanding variation in NSAID utilization during the pandemic’s health service disruptions can provide insight into drivers of high-risk use and inform multilevel efforts to reduce NSAID overuse.

In the present study, we evaluated utilization of high-risk prescription NSAIDs among a large cohort of Virginia patients with CKD, HF, and/or HTN from 2019 to 2021. We hypothesized that (1) high-risk NSAID utilization was prevalent across the cohort, (2) high-risk NSAID utilization rates were greater in rural vs urban areas, and (3) the COVID-19 pandemic was associated with an increase in high-risk NSAID utilization in both rural and urban areas due to barriers to the use of nonpharmacological pain therapies.

METHODS

This retrospective cohort study used data from the Virginia All-Payer Claims Database (APCD), which includes insurance claims for more than 5 million Virginians covered by multiple public and private payers.¹⁹ We limited this study to adult patients who had both medical and pharmaceutical claims on record for 2019, 2020, and 2021. Based on the use of deidentified data, this study was deemed non–human subjects research by Carilion Clinic’s Institutional Review Board.

Procedures

From APCD claims aggregated by patient demographic characteristics, we established a study cohort of adult ( ≥ 18 years) patients who were continuously enrolled with commercial, Medicare Advantage, or Medicaid payers for at least 12 retrospective months during 2019, 2020, and 2021. Traditional Medicare and dual-eligible patients were excluded because Medicare Part D (pharmaceutical) claims were unavailable. We identified claims for NSAID prescriptions filled by patients with a diagnosis of CKD, HF, and/or HTN on record during the previous 12 months. eAppendix File 1 (eAppendix available at ajmc.com) includes names of the specific NSAIDs included in the analysis and the diagnosis codes used to identify CKD, HF, and/or HTN. Patients with CKD were limited to those with a diagnosis of stage 3 CKD or worse due to the recognized underdocumentation of stages 1 and 2 in the medical record.

For this study, we defined high-risk NSAID use as 2 or more orders for oral NSAIDs prescribed to patients with CKD, HF, and/or HTN over the previous 12 months, as informed by Choosing Wisely.⁹ Using the MedInsight Health Waste Calculator version 7.2 (Milliman MedInsight), we categorized prescription NSAID claims as either high risk or clinically indicated, as described previously.^20,21 All claims for aspirin were considered clinically indicated (to avoid misclassification of prophylactic use), as were those associated with topical NSAIDs. All other NSAIDs prescribed for patients with CKD stage 3 or worse, HF, and/or HTN were categorized as high risk.

We calculated the bimonthly utilization rate per 1000 patients for high-risk and clinically indicated NSAID prescription claims between 2019 and 2021. Results were stratified by rurality using Rural-Urban Commuting Area (RUCA) codes (RUCA 1-3: urban; 4-10: rural),²² age, and biological sex (gender data are not available in the APCD). We extrapolated high-risk NSAID utilization results to the population of insured adults in Virginia (5.9 million).²³

Statistical Analysis

To evaluate the effect of the pandemic on NSAID utilization rates during 2020-2021, we used a heterogeneous difference-in-differences (DiD) design, allowing the pandemic DiD effect to vary within subpopulations defined by rurality, age, and sex. Poisson regression models were fit for high-risk and clinically indicated utilization rates. Predicted utilization rates were estimated using model predictions with the absence of the DiD effect. An autoregressive correlation structure (ie, AR1) was implemented to account for the correlation between neighboring month-pairs and a linear year term, and categorical month-pair terms were applied to account for annual and secular trends in both models. Resulting models were expressed as incidence rate ratios (IRRs), and interaction effects were calculated using predicted marginal means with population ratios matching the study sample. All statistical analyses were performed using the geepack (v1.3.11) and emmeans (v1.10.2) libraries within R 4.4.1 (R Foundation for Statistical Computing).

RESULTS

Our study cohort included 1.3 million patients (mean age, 57.6 years; 56% female; 15% rural) (eAppendix File 2). Demographic characteristics remained stable from 2019 to 2021, with the exception of insurer. Mirroring state and national trends, the proportion of patients covered by commercial insurers decreased and the proportion enrolled in Medicaid increased between 2019 and 2021.²⁴

Of the NSAID prescriptions utilized by patients with CKD, HF, and/or HTN from 2019 to 2021, 82.1% were categorized as high risk. Extrapolated to the statewide population of insured adults, 3,841,000 high-risk NSAID prescriptions were filled by Virginians between 2019 and 2021. Unadjusted high-risk NSAID utilization rates were greater among women than men (60.4 vs 48.3 prescriptions per 1000 patients) and in patients aged 40 to 64 and 65 to 79 years (75.6 and 72.8 prescriptions per 1000 patients) vs those aged 80 years and older and aged 18 to 39 years (55.8 and 12.0 prescriptions per 1000 patients, respectively) (eAppendix Files 3 and 4).

High-Risk NSAID Utilization in Rural vs Urban Areas

When controlling for demographics, high-risk NSAID utilization was 59.4% higher in rural vs urban areas from 2019 to 2021 (IRR, 1.594; 95% CI, 1.408-1.803; P < .001) (Table). Our model also identified a significant interaction between rurality and biological sex: High-risk NSAID utilization was 12.1% higher in women relative to men in rural areas, but 28.5% higher in women vs men in urban areas (eAppendix File 5) (P = .007). The interaction between rurality and age was nonsignificant (Table and eAppendix File 5).

The Impact of the COVID-19 Pandemic on High-Risk NSAID Utilization

Compared with prepandemic (2019) utilization rates, unadjusted high-risk NSAID utilization declined from 64.8 prescriptions per 1000 patients to 49.7 prescriptions per 1000 patients between 2020 and 2021 (Figure). Our model indicated a significant pandemic (DiD) effect (IRR, 0.882; 95% CI, 0.814-0.955; P = .002) as well as a significant interaction between the pandemic (DiD) and age (P < .001). The pandemic moderated the effect of age on high-risk NSAID utilization such that, compared with patients aged 18 to 39 years, those 40 years and older experienced a greater decline in high-risk NSAID utilization (eAppendix File 6). The pandemic (DiD) * rurality and pandemic (DiD) * biological sex interactions were nonsignificant (Table and eAppendix File 6). Model results for clinically indicated NSAID utilization are shown in eAppendix Files 7-10.

DISCUSSION

This analysis of claims data for more than 1 million Virginians identified a modest decline in high-risk NSAID utilization rates during the first 2 years of the COVID-19 pandemic compared with prepandemic rates. Although this reduction in potentially harmful utilization is encouraging, the estimated overall volume of high-risk NSAIDs prescribed (~3.8 million prescriptions statewide in 2019-2021) and the persistent disproportionate utilization in rural areas (59% higher rates than urban areas) and among women (25% higher rates than men) highlight the need for clinical, organizational, and policy-level efforts to improve the quality and equity of pain management for Virginians with CKD, HF, and HTN—increasingly prevalent chronic conditions.²⁵

We hypothesized that high-risk NSAID utilization increased throughout the first 2 years of the pandemic due to reduced access to nonpharmacological pain therapies, as has been reported for opioids and other health services.^15,26 However, similar to Levine et al,¹⁸ who identified reduced high-risk NSAID utilization during the first pandemic surge in 2020, we observed decreased NSAID use among patients with CKD, HF, and/or HTN between 2020 and 2021. Further research is needed to identify the mechanism for this observation. It is unlikely that decreased utilization was driven by reduced prevalence of chronic pain, as there is evidence that chronic pain rates increased substantially during the pandemic.²⁷ One possibility is reduced health care access during 2020 and 2021, although other studies have identified minimal impact of the pandemic on prescription medication utilization.^13,14 Clinicians may have improved compliance with evidence-based recommendations to limit or avoid NSAIDs in patients with CKD, HF, and/or HTN amid the enhanced risk presented by the pandemic. Public perception of the influence of NSAIDs on COVID-19 risk or prognosis may have also led to decreased high-risk NSAID utilization. Early pandemic reports suggested that NSAIDs suppressed immune function and upregulated angiotensin-converting enzyme receptors (facilitating cellular entry for SARS-CoV-2).²⁸ Although the World Health Organization and others reported no strong evidence linking NSAIDs to COVID-19,²⁹ the increased attention (eg, 100% rise in related Google searches in March 2020³⁰) may have influenced utilization behaviors.

The study is among the first to identify disparate rates of high-risk NSAID utilization in rural vs urban areas. The greater prevalence of CKD, HF, and HTN and the higher average age of residents in rural areas offer only a partial potential explanation. Limited availability of pain specialists and nonpharmacological pain therapies (eg, physical therapy, acupuncture) in rural vs urban areas is a potential contributor.^2,3,5 Because rural Virginia has experienced some of the greatest impacts of the opioid epidemic,³¹ increased high-risk NSAID utilization may reflect an unintended consequence of efforts to deprescribe opioids. Policy makers should prioritize the expansion of access to safer pain management options in rural areas and consider focused efforts to monitor the relationship between opioid deprescribing and use of other low-value/high-risk therapies.

Although high-risk NSAID utilization decreased proportionally in rural and urban areas between 2020 and 2021, patients 40 years and older experienced a greater decline in utilization than younger patients. Although decreased high-risk use is encouraging, the trend may reflect reduced access to or utilization of high-value health services during the first 2 years of the pandemic, as reported by others.³² For example, patients who were unable to access primary care may have experienced lower rates of high-risk NSAID utilization concurrent with interruptions in high-value medications and other preventive services, which may have important short- and long-term implications for older adults’ health outcomes. It is unclear why biological sex differences (elevated high-risk utilization among women) were greater in urban vs rural areas, but sex-based variation in NSAID use during the pandemic has also been reported elsewhere.³³

Limitations

This study has several limitations. First, although the cohort included patients covered by 3 major insurers, findings may not generalize to uninsured patients or those with other insurance coverage. Second, despite adjustment for demographic changes over time, some changes in high-risk NSAID utilization may have been incorrectly attributed to the pandemic. Third, the MedInsight Health Waste Calculator classifies NSAID use among patients with CKD (stage 3 or worse), HF, and/or HTN as low value (high risk); however, recommendations vary across guidelines, and individual risk may differ by disease characteristics, disease control, concurrent medications, and other clinical factors. Fourth, available claims data lacked information on dose, strength, days’ supply, quantity dispensed, specific NSAID, and clinical decision-making, limiting assessment of more nuanced changes in prescribing patterns. Finally, insurance claims do not capture over-the-counter NSAID use, which may underestimate overall NSAID utilization. Despite these limitations, we are confident that the broad, population-level approach applied is appropriate for assessing the overall landscape of prescription NSAID utilization among patients with CKD, HF, and/or HTN, as in other published studies.^20,21 Future research may evaluate within-population utilization patterns.

CONCLUSIONS

NSAIDs, which are among the most common medications used worldwide, pose cardiovascular and renal risk for patients with CKD, HF, and/or HTN.⁹ Although NSAID utilization decreased modestly among our cohort of more than 1 million patients with CKD, HF, and/or HTN during the COVID-19 pandemic, the high overall utilization (an estimated 3.8 million prescriptions statewide in 2019-2021) and disproportionate utilization in rural areas (~60% higher than urban areas), among female patients, and among older adults suggest an opportunity to enhance the quality and equity of NSAID prescribing in Virginia.

Acknowledgments

The authors thank Kyle Russell and Jillian Rider from Virginia Health Information for their generous collaboration and expertise with the Virginia All-Payer Claims Database, Beth Bortz from the Virginia Center for Health Innovation for her support of efforts to reduce low-value care in Virginia, and Emily Cox and Orchid Tucker from the Carilion Clinic for their assistance with data management and manuscript preparation.

Author Affiliations: Department of Family and Community Medicine, Carilion Clinic (MSR, JKT, JWE), Roanoke, VA; Virginia Tech Carilion School of Medicine (MSR, MV, IY, JWE), Roanoke, VA; Center for Biostatistics and Health Data Science, Virginia Tech (CG, ALH), Roanoke, VA; Translational Biology, Medicine, and Health Graduate Program, Virginia Tech (JKT), Roanoke, VA.

Source of Funding: This research was funded, in part, by the Virginia Tech University Libraries Collaborative Research Grant.

Author Disclosures: Dr Epling reports receiving an internal CTSA grant to conduct further research on sludge. The remaining authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (MSR, MV, ALH, JWE); acquisition of data (MSR, MV); analysis and interpretation of data (MSR, CG, IY, ALH, JWE); drafting of the manuscript (MSR, CG, JKT, MV, IY, JWE); critical revision of the manuscript for important intellectual content (CG, MV, IY, JWE); statistical analysis (CG); obtaining funding (MSR); administrative, technical, or logistic support (JKT, JWE); supervision (MSR, ALH, JWE); and data visualization (JKT).

Address Correspondence to: Michelle S. Rockwell, PhD, RD, Virginia Tech Carilion School of Medicine, 1 Riverside Circle, Ste 102, Roanoke, VA 24016. Email: msrock@vt.edu.

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