Reactions 1435 - 19 Jan 2013

Antihypertensive/NSAID tripletherapy ups risk of kidney injuryWhile double therapy with an antihypertensive and an

NSAID does not appear to be associated with acutekidney injury, triple therapy with two antihypertensivesand an NSAID increases the risk of acute kidney injuryby almost one third, according to findings published inthe BMJ.1

Canadian researchers, Francesco Lapi and colleagues,conducted a nested case-control analysis using datafrom a cohort of nearly 490 000 antihypertensive userson the UK Clinical Practice Research Datalink (CPRD) –formerly known as the General Practice ResearchDatabase (GPRD).

Over a mean follow-up of approximately 6 years,2215 cases of acute kidney injury were identified,equating to an incidence of approximately 7 per10 000 person-years. Use of a diuretic plus an NSAID,and use of an ACE inhibitor or angiotensin receptorblocker (ARB) plus an NSAID, was not associated withan increased risk of acute kidney injury; however, use ofa diuretic, plus an ACE inhibitor or ARB, plus an NSAIDwas associated with a rate of acute kidney injury 31%higher than use of an antihypertensive alone (rate ratio1.31; 95% CI 1.12, 1.53).

The associated risk of acute kidney injury wasparticularly high at the start of treatment. Triple therapyrecipients showed an 82% increased risk during the first30 days of use; the adjusted rate ratio progressivelydecreased thereafter and was no longer statisticallysignificant after > 90 days of use (1.01; 0.84, 1.23).

Hypertensive patients often require more than oneantihypertensive to control their BP, and use ofantihypertensives in combination with NSAIDs iscommon, as many patients experience comorbidchronic inflammatory diseases or chronic pain. Whileobservational evidence, in the past, has suggested a linkbetween combination therapy and acute kidney disease,a causal association has been difficult to establish, as it’sconfounded by indication; i.e. patients who areprescribed combination therapy are generally at a higherrisk of acute kidney injury.

In an accompanying editorial, Dorothea Nitsch andLaurie A Tomlinson, of the London School of Hygieneand Tropical Medicine, state that the wide confidenceintervals and failure to account for OTC NSAID use,among other study limitations, mean that Lapi et al.probably underestimate the true burden of drugassociated acute kidney injury.2 The commentators pointto evidence of an early increase in risk with a diureticplus NSAID combination, and conclude that "The jury isstill out on whether double drug combinations areindeed safe".1. Lapi F, et al. 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.BMJ 346: [11 pages], No. e8525, 8 Jan 2013. Available from: URL: http://dx.doi.org/10.1136/bmj.e8525.

2. Nitsch D, et al. Safety of coprescribing NSAIDs with multiple antihypertensiveagents. BMJ 346: [2 pages], No. e8713, 8 Jan 2013. Available from: URL: http://dx.doi.org/10.1136/bmj.e8713.

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Reactions 19 Jan 2013 No. 14350114-9954/10/1435-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved