Increased Creatinine after Starting ACEIs/ARBs May Increase Cardiorenal Risk

Patients who have even relatively small increases in creatinine after starting angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) treatment are at increased risk of adverse cardiorenal events, suggests a study in the British Medical Journal.

Using linked UK primary care and hospital databases, the researchers identified 122,363 patients who initiated treatment with ACEIs or ARBs between 1997 and 2014. Of these, 1.7% had creatinine increases of 30% or more after starting renin-angiotensin system blockade. Rates of end stage renal disease, myocardial infarction, heart failure, and death were compared for patients with and without a 30% increase in creatinine, with adjustment for patient characteristics and clinical factors. Differences in risk per 10% increase in creatinine after starting ACEI/ARB therapy were evaluated as well.

Patients with creatinine increases of 30% or greater were older, median age 68 versus 63 years; more likely to be female, 56.1% versus 46.1%; and more likely to have stage 3b or 4 chronic kidney disease, 8.9% versus 4.3%. This group also had higher rates of myocardial infarction, heart failure, arrhythmias, and peripheral artery disease and were more likely to be taking loop or potassium-sparing diuretics and nonsteroidal anti-inflammatory drugs.

Rates of all adverse cardiorenal outcomes were significantly higher for the patients with a 30% or greater increase in creatinine, compared to those with increases of less than 30%. Adjusted incidence rate ratios were 3.43 for ESRD, 1.46 for myocardial infarction, 1.37 for heart failure, and 1.87 for death. These increases were greatest in the year after starting ACEI/ARB treatment.

Among those with lesser increases in creatinine, all risks increased in graduated fashion. In patients with creatinine increases of 10% to 19% up to 40% or higher, IRRs increased steadily: from 1.73 to 4.04 for ESRD, 1.12 to 1.59 for myocardial infarction, 1.14 to 1.42 for heart failure, and 1.15 to 2.11 for mortality (compared to creatinine increases of less than 10%).

Some patients experience a sudden drop in kidney function after starting ACEI/ARB therapy. Creatinine increases of up to 30% are generally regarded as safe, and even as an indicator of preserved renal function. The authors sought to determine the long-term implications of increased creatinine, including increases of less than 30%.

The results suggest significant increases in cardiorenal events and mortality for patients with increases in creatinine after starting ACEI/ARB treatment. The increased risks are apparent even under the 30% threshold, in “dose-response” fashion. The investigators conclude, “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” [Schmidt M, et al. Serum creatinine elevation after renin-angiotensin system blockade and long term cardiorenal risks: cohort study. BMJ 2017; 356: j791].

April 2017 (Vol 9, Number 4)