Even small reductions in kidney function after starting common blood pressure drugs are associated with increased risk

03 Apr 2017

Angiotensin converting enzyme inhibitors (ACEI) (drugs with names ending in –pril, e.g. enalapril) and angiotensin receptor blockers (ARB) (drugs with names ending in –sartan, e.g. losartan) are drugs that are commonly used to treat high blood pressure and heart failure. Current guidelines recommend that they should be stopped in people who have a reduction in kidney function (measured using serum creatinine: increased serum creatinine indicates reduced kidney function) of 30% or more after starting them.

We used real-world data (from routinely-collected general-practice electronic health records) from over 120,000 UK patients who were started on treatment with an ACEI or an ARB. We found that decreases in kidney function after starting ACEI/ARBs were linked to poor health outcomes in a graduated relationship; greater decline in kidney function was related to higher risk of death, heart attack, heart failure, and end-stage renal disease. So, even below the guideline recommended threshold for stopping the drugs (of 30% reduction in kidney function) we saw increased risk of poor health outcomes (Figure 1).

Figure 1. Cardiorenal risks associated with levels of creatinine increase (reduction in kidney function) after renin-angiotensin system blockade (starting ACEI/ARB)
From doi: https://doi.org/10.1136/bmj.j791

The question then is: does this mean that ACEI/ARB drugs should be stopped in anyone with even a small decrease in kidney function after starting them? Well, this isn’t an easy question to answer. It is clear that increases below 30% can’t be viewed as safe, however, it’s unclear whether ACEI/ARB associated changes in renal function simply unmask existing kidney dysfunction or lead directly to poor outcomes by causing kidney impairment. Also, we don’t yet fully understand the interplay between the overall risks and benefits of these drugs. It might be that any potential harms are outweighed by their overall benefits (i.e. through the management of the conditions that they are used to treat).

What is certain is that patients with any decline in kidney function after starting ACEI/ARB treatment should be recognised as a very high-risk group who need close ongoing monitoring. Doctors should carefully consider the potential benefits of continuing drug treatment for each individual patient.

Read the full paper here: http://www.bmj.com/content/356/bmj.j7917

Or the linked commentary http://www.bmj.com/content/356/bmj.j1122

Schmidt M, Mansfield KE, Bhaskaran K, Nitsch D, Sørensen HT, Smeeth L, Tomlinson LA. Serum creatinine elevation after renin-angiotensin system blockade and long term cardiorenal risks: cohort study. BMJ. 2017 Mar 9;356:j791.