Hyperkalemia and Risk of RAAS Inhibitor Treatment Cessation

Nephrology Dialysis Transplantation. doi.org/10.1093/ndt/gfz263

There are few data available regarding the rates of hyperkalemia in users of renin angiotensin aldosterone system (RAAS) inhibitors and factors associated with treatment interruptions and cessation.

Researchers, led by James B. Wetmore, MD, MS, identified RAAS inhibitor users in the linked UK Clinical Practice Research Datalink-Hospital Episodes Statistics data set, from 2009 to 2015. Treatment interruptions were defined as no active prescription followed by reappearance. Interruptions and cessations were examined. Hyperkalemia was defined as serum potassium >5.5 mmol/L.

Time-varying Cox regression models were used to calculate rates of hyperkalemia and the factors associated with interruptions and cessations; hyperkalemia was included as a time-dependent variable.

The data set revealed 434,027 users of RAAS inhibitors. Among those, the rate of hyperkalemia was 1.30 (95% confidence interval [CI], 1.28-1.32) per 100 patient-years. A total of 73.7% of patients experienced periods of off treatment. Of those, 57.6% experienced interruption, 7.5% experienced cessation, and 8.6% experienced both interruption and cessation. Approximately one-third of patients experienced interruption or cessation within 1 year of initiation of RAAS inhibitor treatment.

The hazard ratios for patients with severe hyperkalemia were 1.10 (95% CI, 1.05-1.16) for treatment interruptions and 3.37 (95% CI, 3.25-3.50) for treatment cessation. In comparison with individuals with no chronic kidney disease (CKD), the risks of interruption for stages 4 and 5 were 1.20 (95% CI, 1.16-1.25) and 1.57 (95% CI, 1.44-1.72), respectively. The risks of cessation were 2.20 (95% CI, 2.07-2.33) and 2.87 (95% CI, 2.56-3.22), respectively.

For patients with heart failure and diabetes, the risks of interruption increased: 1.04 (95% CI, 1.02-1.05) and 1.13 (95% CI, 1.12-1.14), respectively. However, the risk of cessation decreased in patients with heart failure and diabetes: 0.85 (95% CI, 0.82-0.87) and 0.92 (95% CI, (0.90-0.94), respectively.

The researchers said, “Risk of RAAS inhibitor interruption and cessation increased as CKD stage progressed. Efforts targeting reasons for interruptions and, especially, cessations, such as hyperkalemia prevention, could decrease off-treatment periods for patients who would otherwise benefit, such as those with CKD, heart failure, or diabetes.”