Combination therapy with antihypertensives, painkillers heightened kidney failure risk

Triple combination therapy with antihypertensive agents and nonsteroidal anti-inflammatory drugs may increase risk for acute kidney injury, particularly when treatment is first initiated, according to data published in BMJ.

Using the Clinical Practice Research Datalink (CPRD) in the United Kingdom, researchers studied 487,372 users of antihypertensive medication for a mean of 5.9 years. During that time, 2,215 cases of acute injury occurred, with an overall incidence rate of 7 per 10,000 person-years, researchers reported in the study.

The results show that double therapy with a diuretic, an ACE inhibitor or an angiotensin receptor blocker and an NSAID was not linked to an increased rate of acute kidney injury. However, researchers discovered a 31% increase in the rate of acute kidney injury in patients taking a triple combination of a diuretic with an ACE inhibitor or an angiotensin receptor blocker and an NSAID (95% CI, 1.12-1.53). Secondary analyses indicate that the rate was 82% higher within the first 30 days of use (95% CI, 1.35-2.46).

“Given that NSAIDs are widely used and that a greater incidence rate of acute kidney injury was estimated among antihypertensive drug users than in the general population, increased vigilance may be warranted when diuretics and ACE inhibitors or [angiotensin receptor blockers] are used concurrently with NSAIDs,” investigator Francesco Lapi, PharmD, PhD, of the Lady Davis Institute at Jewish General Hospital in Montreal, and colleagues wrote in the study. “In particular, major attention should be paid early in the course of treatment, and a more appropriate choice among the available anti-inflammatory or analgesic drugs could therefore be applied in clinical practice.”

In an accompanying editorial in the same issue of BMJ, Dorothea Nitsch, MD, MSc, and Laurie A. Tomlinson, MD, both from the London School of Hygiene and Tropical Medicine, supported the study despite its limitations.

“The implications of the current analysis are nevertheless important: Clinicians must advise patients who are prescribed diuretics, ACE inhibitors, or [angiotensin receptor blockers] of the risk associated with NSAID use and they must also be vigilant for signs of drug-associated acute kidney injury in all patients,” they wrote.

For more information:

Lapis F. BMJ. 2013;doi:10.1136/bmj.e8525.

Nitsch D. BMJ 2013;doi:10.1136/bmj.e8713.

Disclosure: See the full study for a list of the researchers’ relevant financial disclosures. Nitsch reports no relevant financial disclosures.