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Original Investigation
Less Is More
November 2018

Frequency and Associations of Prescription Nonsteroidal Anti-inflammatory Drug Use Among Patients With a Musculoskeletal Disorder and Hypertension, Heart Failure, or Chronic Kidney Disease

Author Affiliations
  • 1Institute for Health Systems Solutions and Virtual Care, Women’s College Hospital, Toronto, Ontario, Canada
  • 2Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
  • 3Institute for Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
  • 4Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada
  • 5Division of Nephrology, University Health Network, Toronto, Ontario, Canada
  • 6Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
  • 7Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  • 8Toronto General Research Institute, Toronto General Hospital, Toronto, Ontario, Canada
  • 9Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  • 10Health Quality Ontario, Toronto, Ontario, Canada
JAMA Intern Med. 2018;178(11):1516-1525. doi:10.1001/jamainternmed.2018.4273
Key Points

Question  What are the frequency and associations of nonsteroidal anti-inflammatory drug (NSAID) use among patients with hypertension, heart failure, or chronic kidney disease?

Findings  Among a retrospective cohort of more than 2.4 million musculoskeletal-related primary care visits by 814 049 older adult patients with hypertension, heart failure, or chronic kidney disease, 9.3% of visits resulted in prescription NSAID use within the following 7 days. Prescription NSAID use was not associated with increased risk of safety-related outcomes at 37 days.

Meaning  Prescription NSAID use was common among high-risk patients, with widespread physician-level variation; however, use had no association with acute safety-related outcomes.


Importance  International nephrology societies advise against nonsteroidal anti-inflammatory drug (NSAID) use in patients with hypertension, heart failure, or chronic kidney disease (CKD); however, recent studies have not investigated the frequency or associations of use in these patients.

Objectives  To estimate the frequency of and variation in prescription NSAID use among high-risk patients, to identify characteristics associated with prescription NSAID use, and to investigate whether use is associated with short-term, safety-related outcomes.

Design, Setting, and Participants  In this retrospective cohort study, administrative claims databases were linked to create a cohort of primary care visits for a musculoskeletal disorder involving patients 65 years and older with a history of hypertension, heart failure, or CKD between April 1, 2012, and March 31, 2016, in Ontario, Canada.

Exposure  Prescription NSAID use was defined as at least 1 patient-level Ontario Drug Benefit claim for a prescription NSAID dispensing within 7 days after a visit.

Main Outcomes and Measures  Multiple cardiovascular and renal safety-related outcomes were observed between 8 and 37 days after each visit, including cardiac complications (any emergency department visit or hospitalization for cardiovascular disease), renal complications (any hospitalization for hyperkalemia, acute kidney injury, or dialysis), and death.

Results  The study identified 2 415 291 musculoskeletal-related primary care visits by 814 049 older adults (mean [SD] age, 75.3 [4.0] years; 61.1% female) with hypertension, heart failure, or CKD, of which 224 825 (9.3%) were followed by prescription NSAID use. The median physician-level prescribing rate was 11.0% (interquartile range, 6.7%-16.7%) among 7365 primary care physicians. Within a sample of 35 552 matched patient pairs, each consisting of an exposed and nonexposed patient matched on the logit of their propensity score for prescription NSAID use (exposure), the study found similar rates of cardiac complications (288 [0.8%] vs 279 [0.8%]), renal complications (34 [0.1%] vs 33 [0.1%]), and death (27 [0.1%] vs 30 [0.1%]). For cardiovascular and renal-safety related outcomes, there was no difference between exposed patients (308 [0.9%]) and nonexposed patients (300 [0.8%]) (absolute risk reduction, 0.0003; 95% CI, −0.001 to 0.002; P = .74).

Conclusions and Relevance  While prescription NSAID use in primary care was frequent among high-risk patients, with widespread physician-level variation, use was not associated with increased risk of short-term, safety-related outcomes.

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    1 Comment for this article
    Potentially missleading results
    Adrienne Mims, MD, MPH, AGSF, FAAFP | Vice President, Chief Medical Officer, Alliant Health Solutions - QIN-QIO for Georgia and North Carolina
    I have concerns that the conclusions are misleading and could result in patient harm. Some people may only read the summary and think that it is now safe to more broadly use NSAIDS in patients with CKD and heart failure at any stage of disease severity.

    First- The authors chose to exclude patients who filled their prescription or were hospitalized with the primary outcome in 7 days. This reason for exclusion of a large proportion of the subjects is not valid. Rather, a great many patients do fill their prescriptions within 7 days
    and thus those outcomes should be accounted for in the conclusion.

    Second - You note that the methods for comparing study subjects cannot control for disease severity (severity of CKD or heart failure). Thus an alternate explanation for the results is that those prescribed NSAIDS had early disease and thus less likely to have a bad outcome.

    Third - From the data provided, you note that those patients with heart failure or CKD were more likely to NOT be prescribed an NSAID. This is consistent with recommendations and may be why less hospitalizations and emergency visit occurred during the time period of observation.

    Fourth - Your data notes a decline in NSAID prescribing to these patients over the time period of the study. Thus, an alternative conclusion is that clinicians are appropriately not prescribing NSAIDs to those with advanced disease and at high risk for hospitalization and emergency room visits.

    Given the wide variation on amounts of NSAIDs prescribed, and the subgroup of those clinicians writing for NSAIDs in this population, this study instead identifies those physicians most in need of hearing the Choosing Wisely message.