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Antihypertensive Therapy plus Nonsteroidal Anti-Inflammatory Drugs Contribute to Risk for Kidney Injury

Triple therapy (a diuretic + an angiotensin-converting–enzyme inhibitor or angiotensin-receptor blocker + an NSAID) was associated with excess risk.

Patients with hypertension often have conditions for which nonsteroidal anti-inflammatory drugs (NSAIDs) are indicated. However, both NSAIDs and certain antihypertensive drugs (i.e., diuretics, angiotensin-converting–enzyme [ACE] inhibitors, and angiotensin-receptor blockers [ARBs]) have hemodynamic effects on the kidney. Investigators retrospectively studied a U.K. database to examine whether antihypertensive therapy in combination with regular NSAID use is associated with excess risk for acute kidney injury.

Nearly 490,000 users of antihypertensive drugs were included in the study. During a mean follow-up of 5.9 years, >2200 cases of kidney injury were identified (defined as first hospital admission related to kidney injury). Adjusted for multiple confounders, double therapy (an NSAID, plus either a diuretic, an ACE inhibitor, or an ARB) was not associated with any greater likelihood of kidney injury than was an antihypertensive drug alone. In contrast, triple therapy (an NSAID, plus a diuretic, plus an ACE inhibitor or an ARB) significantly heightened the incidence of kidney injury compared with the same therapy without an NSAID (rate ratio, 1.3). Notably, highest risk was observed during the first 30 days of triple therapy.

Comment: In this large retrospective study, triple therapy with a diuretic plus an ACE inhibitor or an ARB plus an NSAID was associated with significant excess risk for kidney injury. These results are biologically plausible: Volume contraction caused by diuretics and renal efferent arteriole dilatation caused by ACE inhibitors and ARBs, together with renal afferent arteriole constriction caused by NSAIDs (due to inhibition of prostacyclin synthesis), likely accounts for the excess risk.

— Paul S. Mueller, MD, MPH, FACP

Published in Journal Watch General Medicine February 8, 2013

Citation(s):

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 2013 Jan 8; 346:e8525. (http://dx.doi.org/10.1136/bmj.e8525)

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Reader Remarks:

Review and add to remarks on this article

• bad drug combo!
  George B Howell, MD, 13 Feb 2013 11:21 AM EST
  Specialty: Family Medicine
  thanks for the tip!
• broad categorizations
  E Ward, 5 Mar 2013 1:12 PM EST
  Specialty: Family Medicine
  The original article, http://www.bmj.com/content/346/bmj.e8525, offers no comparison by age and includes all NSAIDs--which means patients on ASA also. Triple therapy... [more]

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