Risk–Benefit Balance of Renin–Angiotensin–Aldosterone Inhibitor Cessation in Heart Failure Patients with Hyperkalemia


Heart failure (HF) is a chronic medical condition that occurs when the heart is unable to pump enough blood to meet the body’s needs. It is a serious health concern that affects millions of people worldwide. In recent years, the Renin-Angiotensin-Aldosterone System (RAAS) has become a target for HF treatment. The RAAS system is a complex hormonal pathway that plays a crucial role in regulating blood pressure, fluid balance, and electrolyte homeostasis.

Inhibitors of the RAAS system, including Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs), have been shown to improve outcomes in patients with HF. They work by blocking the effects of angiotensin II and reducing its harmful effects on the heart and blood vessels. These drugs have been shown to improve symptoms, reduce hospitalizations, and improve survival in patients with HF. In addition to ACEIs and ARBs, another class of drugs called mineralocorticoid receptor antagonists (MRA) has also been shown to be effective in treating HF.

The combination of ACEIs or ARBs with MRA has been shown to provide even greater benefits in patients with HF. This combination is known as a Renin-Angiotensin-Aldosterone Inhibitor (RAASi) therapy. RAASi therapy has been shown to reduce hospitalizations, improve symptoms, and increase survival in patients with HF.

However, RAASi therapy is not without its potential side effects. In particular, they can cause electrolyte imbalances, such as high potassium levels, which can lead to a dangerous condition that requires medical intervention in some patients. Therefore, patients taking RAASi therapy should be monitored closely by their healthcare provider to ensure that they are taking the appropriate dose and that their blood pressure and electrolyte levels are within a safe range.

Recently, a new study published in the peer-reviewed Journal of Clinical Medicine by AstraZeneca scientists: Dr. Suguru Okami, Dr. Naru Morita and Dr. Toshitaka Yajima together with Dr. Shun Kohsaka from Keio University School of Medicine investigated the impact of hyperkalemia on ACEi, ARB, and MRA treatment in patients with HF. The study assessed the ACEi/ARB/MRA treatment dose in hyperkalemic HF patients at baseline and the subsequent effect of RAASi cessation due to hyperkalemia on clinical outcomes. The researchers also assessed the risk-benefit balance of discontinuing RAASi (all ACEi/ARB/MRA) or MRA based on serum potassium levels in hyperkalemic HF patients. The study was ultimately aimed to determine the best course of treatment for these patients.

The study found that the use of RAAS inhibitors in hyperkalemic HF patients was suboptimal, with a high rate of dose reduction and cessation. When compared to individuals who did not stop taking the medicine, the authors showed that stopping RAAS inhibitors or MRA was linked to a number of unfavourable clinical outcomes. The study also suggested that the risks of RAAS inhibitor or MRA cessation outweighed the benefits in patients with mild to moderate hyperkalemia. The findings revealed that compared to those who continued to take the drug, individuals who stopped taking RAAS inhibitor therapy had a considerably greater risk of hospitalization and a tendency towards a higher risk of in-hospital death.

It is, however, important to quote that the study only evaluated the effects of stopping RAAS inhibitors when compared to the group receiving inadequate RAAS inhibitors, which may have overestimated the real effects of stopping. Therefore, when optimal RAAS inhibitor treatments are standardized, the impact of RAAS inhibitor cessation may be greater. The study highlights the importance of carefully monitoring and adjusting RAAS inhibitor treatment in hyperkalemic HF patients to avoid adverse clinical outcomes. The findings suggest that the discontinuation of RAAS inhibitors or MRAs should be avoided whenever possible, especially in patients with mild to moderate hyperkalemia.

In conclusion, the authors evaluated the risk-benefit ratio of discontinuing RAASi or MRA therapy in HF patients with hyperkalemia. They advised caution should be taken while controlling hyperkalemia by stopping RAASi or MRA medication in patients with HF, particularly in those with mild to moderate hyperkalemia. Patients with HF should work closely with their healthcare provider to determine if RAASi therapy is appropriate for them and to monitor their response to treatment.


Kohsaka S, Okami S, Morita N, Yajima T. Risk–Benefit Balance of Renin–Angiotensin–Aldosterone Inhibitor Cessation in HF Patients with Hyperkalemia. Journal of Clinical Medicine. 2022;11(19):5828.

Go To Journal of Clinical Medicine.