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Short-Course Systemic and Topical Non-Steroidal Anti-Inflammatory Drugs: Impact on Adverse Renal Events in Older Adults with Co-Morbid Disease

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Abstract

Background

Prolonged systemic non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with adverse renal outcomes among older adults. However, there is scant data regarding the renal safety of topical and short-course systemic NSAIDs. We aimed to evaluate the risk of acute adverse renal outcomes among older adults prescribed topical and short-term systemic NSAIDs.

Methods

We conducted a retrospective cohort study of all older adults, age 60 years and above, who received prescriptions between July 2015 and December 2017 from the largest tertiary hospital and a major public primary care institution in Singapore. Data from 6 months before until 30 days after the first prescription were retrieved from electronic medical records. The primary outcome was the incidence of acute kidney injury (serum creatinine increased >26.5 µmol/L or >50% from baseline) and/or hyperkalemia within 30 days. A multi-variate analysis taking into account age, sex, co-morbidities, baseline-estimated glomerular filtration rate and serum potassium, NSAID route of administration, and concurrent renin-angiotensin-aldosterone system blocker and diuretic prescription was performed to evaluate factors associated with the primary outcome.

Results

We identified 12,773 older adults with incident prescriptions: 3982 (31.2%) received short-course systemic NSAIDs, 3784 (29.6%) received topical NSAIDs, and 5007 (39.2%) did not receive any NSAID. Both short-course systemic NSAIDs (adjusted odds ratio [OR] 1.59, 95% confidence interval [CI] 1.41–1.80, p < 0.001) and topical NSAIDs (adjusted OR 1.48, 95% CI 1.31–1.67, p < 0.001), compared with the no-NSAID group, were independently associated with the primary outcome. Among older adults with co-morbid conditions and prescribed NSAIDs, topical NSAIDs had a reduced odds of 30-day incident acute kidney injury and/or hyperkalemia in diabetes mellitus (adjusted OR 0.78, 95% CI 0.65–1.06, p = 0.007), chronic kidney disease (adjusted OR 0.74, 95% CI 0.60–0.90, p = 0.003), and cardiovascular disease (adjusted OR 0.54, 95% CI 0.37–0.79, p < 0.001), compared with short-course systemic NSAIDs.

Conclusions

NSAIDs increased the risk of acute adverse renal events. Topical NSAIDs, compared with short-course systemic NSAIDs, were associated with a reduced incidence of acute kidney injury and/or hyperkalemia among older adults with additional risk factors.

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Acknowledgements

We thank the SingHealth Health Services Research Center, the SingHealth Research Office, the Research Efficiency Enhancement Program, and the SingHealth Polyclinics Department of Research Administration for administrative support.

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Authors and Affiliations

  1. Department of Renal Medicine, Singapore General Hospital, Academia Level 3, 20 College Road, Singapore, 169856, Singapore

    Cynthia Ciwei Lim, Jia Liang Kwek, Sheryl S. W. Gan & Jason Chon Jun Choo

  2. SingHealth Polyclinic, Singapore, Singapore

    Andrew Teck Wee Ang, Bandy Qiuling Goh & Ngiap Chuan Tan

  3. Health Services Research Unit, Singapore General Hospital, Singapore, Singapore

    Hanis Bte Abdul Kadir

  4. Pharmacy, Singapore General Hospital, Singapore, Singapore

    Puay Hoon Lee

  5. Health Service Research Center, SingHealth, Singapore, Singapore

    Puay Hoon Lee & Sudha Harikrishnan

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  1. Cynthia Ciwei Lim
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Corresponding author

Correspondence to Cynthia Ciwei Lim.

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Funding

This research was supported by the SHF-Foundation Research Grant (SHF/HSRHO014/2017).

Conflicts of interest

Cynthia Ciwei Lim, Andrew Teck Wee Ang, Hanis Bte Abdul Kadir, Puay Hoon Lee, Bandy Qiuling Goh, Sudha Harikrishnan, Jia Liang Kwek, Sheryl S.W. Gan, Jason Chon Jun Choo, and Ngiap Chuan Tan have no conflicts of interest that are directly relevant to the content of this article.

Ethics approval

This study was conducted according to the Declaration of Helsinki. Waiver of informed consent for use of de-identified electronic medical record data was approved by the local institutional review board (2018/2567).

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Not applicable.

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Not applicable.

Availability of data and material

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

Authors’ contributions

CCL, ATWA, TNC, PHL, BQG, KJL, and JC contributed to the study conception and design. Material preparation, data collection, and analysis were performed by CCL, HBAK, and SH. The first draft of the manuscript was written by CCL. All authors read and approved the final manuscript.

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Lim, C.C., Ang, A.T.W., Kadir, H.B.A. et al. Short-Course Systemic and Topical Non-Steroidal Anti-Inflammatory Drugs: Impact on Adverse Renal Events in Older Adults with Co-Morbid Disease. Drugs Aging 38, 147–156 (2021). https://doi.org/10.1007/s40266-020-00824-4

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