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. 2013 Jan 8:346:e8525.
doi: 10.1136/bmj.e8525.

Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study

Francesco Lapi  1 , Laurent Azoulay, Hui Yin, Sharon J Nessim, Samy Suissa
Affiliations

Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study

Francesco Lapi et al. BMJ. .

Abstract

Objectives: To assess whether a double therapy combination consisting of diuretics, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers with addition of non-steroidal anti-inflammatory drugs (NSAIDs) and the triple therapy combination of two of the aforementioned antihypertensive drugs to which NSAIDs are added are associated with an increased risk of acute kidney injury.

Design: Retrospective cohort study using nested case-control analysis.

Setting: General practices contributing data to the UK Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database.

Participants: A cohort of 487,372 users of antihypertensive drugs.

Main outcome measures: Rate ratios with 95% confidence intervals of acute kidney injury associated with current use of double and triple therapy combinations of antihypertensive drugs with NSAIDs.

Results: During a mean follow-up of 5.9 (SD 3.4) years, 2215 cases of acute kidney injury were identified (incidence rate 7/10,000 person years). Overall, current use of a double therapy combination containing either diuretics or angiotensin converting enzyme inhibitors or angiotensin receptor blockers with NSAIDs was not associated with an increased rate of acute kidney injury. In contrast, current use of a triple therapy combination was associated with an increased rate of acute kidney injury (rate ratio 1.31, 95% confidence interval 1.12 to 1.53). In secondary analyses, the highest risk was observed in the first 30 days of use (rate ratio 1.82, 1.35 to 2.46).

Conclusions: A triple therapy combination consisting of diuretics with angiotensin converting enzyme inhibitors or angiotensin receptor blockers and NSAIDs was associated with an increased risk of acute kidney injury. The risk was greatest at the start of treatment. Although antihypertensive drugs have cardiovascular benefits, vigilance may be warranted when they are used concurrently with NSAIDs.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: database acquisitions were funded by the Canadian Institute of Health Research (CIHR) and the Canada Foundation for Innovation; SS has received research grants and participated in advisory board meetings and/or as a speaker at conferences for AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Novartis, Pfizer, and Merck; SJN has received speakers’ honorariums from Baxter Healthcare and Merck Frosst; no other relationships or activities that could appear to have influenced the submitted work.

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Flow chart of study
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References

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