Combination ACE inhibitor therapy increases risk of kidney failure and death

Elderly patients prescribed combination angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) had a higher risk of kidney failure and death, according to a study published in CMAJ (Canadian Medical Association Journal).

This study, by researchers from the University of Alberta and the University of Calgary, sought to determine the safety of combination therapy of ACE inhibitors and ARB in the clinical setting as some randomised trials indicate an increased risk of kidney failure. Randomised trials may over or underestimate the risk of adverse events possibly because of patient selection bias, higher drug doses and increased monitoring.

The researchers looked at 32 312 seniors in Alberta, Canada, aged 65 and older who were prescribed an ACE inhibitor and/or an ARB. They compared patients receiving both drugs together with patients who received only one of the drugs. They found a higher risk of adverse events such as high creatinine levels, end-stage renal disease and death in people taking combination therapy.

'We found that less than one-seventh of the elderly residents of Alberta who were given combination therapy in clinical practice had either of the conditions for which this therapy has been proven beneficial in randomised trials (i.e., proteinuria or symptomatic left ventricular systolic dysfunction despite treatment with and ACE inhibitor or an angiotensin-receptor blocker alone,' writes Dr Finlay McAlister, University of Alberta, with coauthors.

As well, they observed that within three months, most patients stopped the combination therapy. The authors speculate this may have been due to low blood pressure.

'Our most striking findings were that combination therapy was commonly prescribed for patients who did not have the trial-proven indications and that it was frequently stopped after only a few months, even when hyperkalemia or renal dysfunction did not occur,' conclude the researchers.