Factors associated to renin-angiotensin-aldosterone system inhibitors discontinuation or down-titration due to hyperkalaemia in patients with chronic cardiovascular conditions
Authors: Alcoberro L , Jimenez-Marrero S , Cainzos-Achirica M , Monterde D , Enjuanes C , Jose N , Garay A , Moliner P , Yun S , Ramos R , Ras M , Calero E , Hidalgo E , Corbella X , Comin-Colet J 
Published: October 2022

Abstract

Background/Introduction
The renin-angiotensin-aldosterone system inhibitors (RAASI) are one of the keystones of the medical treatment in chronic cardiovascular disorders and have shown improvements in clinical outcomes in many clinical trials. Hyperkalaemia is a well-defined non-desirable effect of RAASI that occasionally forces to interrupt these medications. That enforced RAASI discontinuation or down-titration due to hyperkalaemia may have adverse prognostic consequences.

Purpose
Describe the demographical, clinical and pharmacological variables associated to a higher risk of RAASI discontinuation or down-titration due to hyperkalaemia among individuals with chronic cardiovascular conditions.

Methods
We used data from more than 375,000 individuals 55 years of age or older, included in the population-based healthcare database of a public Institute of Health between 2015 and 2017. We included participants with at least one relevant condition: chronic heart failure, chronic kidney disease, diabetes mellitus, ischemic heart disease or hypertension. They had to be under RAASI treatment as of January 1st, 2016, and with evidence of at least one episode of hyperkalaemia (serum potassium &gt;5.0 mmol/L) during 2016. Then, were classified in one of the two following profiles: RAASI treatment discontinuation or down-titration versus RAASI treatment unchanged or up-titrated. For the statistical analysis, we used logistic regression to calculate the multivariable-adjusted odds ratios of each study variable, comparing RAASI discontinuation or down-titration group to RAASI treatment unchanged or up-titrated controls (reference group).

Results
In the multivariable-adjusted model, the risk of RAASI treatment discontinuation or down-titration due to hyperkalaemia was significantly associated with the use of RAASI, very high comorbidity index, potassium derangements (both hypokalaemia and hyperkalaemia), prior hospitalizations and prior emergency visits. Among RAASI treatments, the use of Angiotensin receptor blockers (OR 2.518, 95% CI 2.317–2.735) and Angiotensin-converting enzyme inhibitors (OR 2.341, 95% CI 2.149–2.549) were associated with a higher risk of RAASI discontinuation or down-titration due to hyperkalaemia than Aldosterone inhibitors (1.428, 95% CI 1.285–1.584).

Conclusion
These results suggest that vulnerable populations such as those with very high comorbidity index, potassium derangements or prior emergency visits or hospitalizations have a higher risk of RAASI treatment discontinuation or down-titration due to hyperkalaemia.
A more careful and exhaustive management of RAASI should be advised in those patients.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Josep Comin-Colet has received speaker fees from Vifor Pharma.