Creatinine increases following initiation of renin-angiotensin-system (RAS) blockade are associated with an increased risk of adverse cardiorenal outcomes, even if those increases are below the guideline-recommended threshold of a 30% increase for discontinuing treatment, according to researchers.

Using the UK’s Clinical Practice Research Datalink, Morten Schmidt, MD, PhD, of London School of Hygiene and Tropical Medicine, in London, UK, and colleagues, examined outcomes among 122,363 patients starting therapy with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) therapy. Of these, 2078 (1.7%) experienced a rise in serum creatinine concentration of 30% or more within 2 months of initiating RAS blockade. Results showed that these patients had a 3.4-fold greater risk for end-stage renal disease (ESRD) and 1.5-, 1.4-, and 1.8-fold increased risk for myocardial infarction, heart failure, and death, respectively, compared with patients who had creatinine increases of less than 30%, the researchers reported in BMJ (2017;356:j791).

When investigators analyzed creatinine elevations in 10% increments, they found graduated cardiorenal risks below the guideline-recommended threshold. Creatinine elevations of 10% to 19% and 20% to 29% were associated with 15% and 35% higher risks of death, respectively, compared with a creatinine increase of less than 10%.

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ACEI/ARB use may be a marker of cardiorenal risks or a cause, according to the researchers. They adjusted results for patient comorbidities, use of other antihypertensive medications and non-steroidal anti-inflammatory drugs (NSAIDs), and socioeconomic factors. They were unable to adjust for proteinuria, however. They noted that more patients with creatinine elevations of 30% or more were elderly and female, had cardiorenal comorbidities, and used NSAIDs, loop diuretics, or potassium-sparing diuretics.

“Increases in creatinine after starting ACEI/ARB treatment identify a high risk group needing close monitoring and in whom the risks and benefits of ACEI/ARB prescribing should be considered,” Dr Schmidt and colleagues wrote in BMJ. Cardiorenal risks were highest in the first year after ACEI/ARB initiation but lasted for up to 10 years. Fewer than 10% of patients in the UK have routine monitoring of creatinine after the start of RAS blockade, according to background information in the study.

The study was based on real clinical practice and confirms data from trial settings.  

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1. Schmidt M, Mansfield KE, Bhaskaran K, et al. Serum creatinine elevation after renin-angiotensin system blockade and long term cardiorenal risks: cohort study. BMJ 2017;356:j791. doi:10.1136/bmj.j791