Stopping Renin-angiotensin inhibitors in hyperkalemia lowers recurrence risk but not CV events

The renin-angiotensin inhibitors (RASi) plays a crucial role in the pathogenesis of hypertension (HTN). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are first line anti-HTN drug classes that are potent, effective and largely safe. Limited observational studies have explored the consequences of stopping RASi in patients experiencing hyperkalemia. Previous studies were limited by inadequate control of confounding, prevalent-user and immortal-time biases or selection of patients hospitalized due to acute heart failure.

An observational study by Dr Yang Xu, Pharm, PhD and team has revealed that stopping RASi after hyperkalemia may be associated with a lower risk of recurrence of hyperkalemia, but it still posed a higher risk of death and cardiovascular events. The decision to stop RASi after hyperkalemia isn't random, however the consequence of complex factors likely have poor outcomes.

The study is published in American Heart Journal.

The objective of the study was to evaluate the effects of stopping RASi in hyperkalemia patients.

The study was observational study from the Stockholm Creatinine Measurements (SCREAM) project including patients initiating RASi in routine care and surviving a first-detected episode of hyperkalemia (potassium >5.0 mmol/L). Target trial emulation techniques based on cloning, censoring and weighting to compare stopping vs. continuing RASi within 6 months after hyperkalemia was used. Outcomes were 3-year risks of mortality, major adverse cardiovascular events (MACE, composite of cardiovascular death, myocardial infarction and stroke hospitalization) and recurrent hyperkalemia.

The results of the study were

• A total of 5669 new users of RASi who developed hyperkalemia (median age 72 years, 44% women), 1425 (25%) stopped RASi therapy within 6 months.

• Compared with continuing RASi, stopping therapy was associated with a higher 3-year risk of death (absolute risk difference 10.8%; HR 1.49, 95% CI 1.34-1.64) and MACE (risk difference 4.7%; HR 1.29, 1.14-1.45), but a lower risk of recurrent hyperkalemia (risk difference -9.5%; HR 0.76, 0.69-0.84).

• Results were consistent for events following potassium of >5.0 or >5.5 mmol/L, after censoring when the treatment decision was changed, across prespecified subgroups, and after adjusting for albuminuria.

Dr Xu, and team concluded that "These findings suggest that stopping RASi after hyperkalemia may be associated with a lower risk of recurrence of hyperkalemia, but higher risk of death and cardiovascular events."

Reference: https://doi.org/10.1016/j.ahj.2021.09.014