Ambulatory Treatments for RAAS Inhibitor–Related Hyperkalemia and the 1-Year Risk of Recurrence

Abstract

Background and objectiveThe optimal ambulatory management of renin-angiotensin-aldosterone system inhibitor (RAASi)–related hyperkalemia to reduce the risk of recurrence is unknown. We examined the risk of hyperkalemia recurrence on the basis of outpatient pharmacologic changes following an episode of RAASi-related hyperkalemia.DesignWe performed a population-based, retrospective cohort study of older adults (n=49,571; mean age 79 years) who developed hyperkalemia (potassium ≥5.3 mEq/L) while on a RAASi and were grouped as follows: no intervention, RAASi discontinuation, RAASi dose decrease, new diuretic, diuretic dose increase, or sodium polystyrene sulfonate within 30 days. The primary outcome was hyperkalemia recurrence, with secondary outcomes of cardiovascular events and all-cause mortality within 1 year.ResultsAmong patients who received a pharmacologic intervention (23% of the cohort), RAASi discontinuation was the most commonly prescribed strategy (74%), followed by RAASi decrease (15%), diuretic increase (7%), new diuretic (3%), and sodium polystyrene sulfonate (1%). A total of 16,977 (34%) recurrent hyperkalemia events occurred within 1 year. Compared with no intervention (35%, referent), the cumulative incidence of recurrent hyperkalemia was lower with RAASi discontinuation (29%; hazard ratio, 0.82; 95% confidence interval, 0.78 to 0.85), whereas there was no difference with RAASi dose decrease (36%; hazard ratio, 0.94; 95% confidence interval, 0.86 to 1.02), new diuretic (32%; hazard ratio, 0.95; 95% confidence interval, 0.78 to 1.17), or diuretic increase (38%; hazard ratio, 0.99; 95% confidence interval, 0.87 to 1.12) and a higher incidence with sodium polystyrene sulfonate (55%; hazard ratio, 1.30; 95% confidence interval, 1.04 to 1.63). RAASi discontinuation was not associated with a higher risk of 1-year cardiovascular events (hazard ratio, 0.96; 95% confidence interval, 0.91 to 1.02) or all-cause mortality (hazard ratio, 1.05; 95% confidence interval, 0.96 to 1.15) compared with no intervention.ConclusionsAmong older adults with RAASi-related hyperkalemia, RAASi discontinuation is associated with the lowest risk of recurrent hyperkalemia, with no apparent increase in short-term risks for cardiovascular events or all-cause mortality.

The Impact of Elective Withdrawal of Long-Term Renin Angiotensin Aldosterone System Blockade in Chronic Kidney Disease Patients with Progressive Acute Kidney Injury: A Prospective 40-Months’ Single-Unit Cohort Study

“…6 Conversely, a Canadian population-based retrospective cohort study investigated the effect of discontinuing RAAS inhibitor in older adults (n=49,571; mean age 79 years) who had developed hyperkalemia (potassium ≥5.3 mEq/L) while on a RAAS inhibitor. 7 The discontinuation of RAAS inhibitor was associated with the lowest risk of recurrent hyperkalemia, with no apparent increase in shortterm risks for cardiovascular events or all-cause mortality. 7 We had in a recent editorial commentary in the American Journal of Medicine raised the concerns that such debate and controversy about cardiorenal outcomes following the discontinuation of RAAS blockade in advanced CKD remain unsettled.…”

“…7 The discontinuation of RAAS inhibitor was associated with the lowest risk of recurrent hyperkalemia, with no apparent increase in shortterm risks for cardiovascular events or all-cause mortality. 7 We had in a recent editorial commentary in the American Journal of Medicine raised the concerns that such debate and controversy about cardiorenal outcomes following the discontinuation of RAAS blockade in advanced CKD remain unsettled. 8 Furthermore, we had earlier described the syndrome of late onset renal failure from angiotensin blockade (LORFFAB) and had demonstrated generally improved renal outcomes in patients presenting with progressive AKI after discontinuation of concurrent RAAS blockade without overt CV consequences.…”

“…[1][2][3][4][5] Nevertheless, there is substantial disagreement regarding the renal and cardiovascular outcomes after the discontinuation of RAAS blockade in patients with advanced CKD. [6][7][8] A recent Swedish Renal Registry study examined the impact of stopping versus continuing RAAS inhibitor therapy in 10,254 prevalent RAAS inhibitor users (median age 72 years, 36% female) with newonset eGFR <30 ml/min per 1.73 m2, 1553 (15%). 6 Median eGFR was 23 ml/min per 1.73 m 2 .…”

Current Management of Hyperkalemia in Non-Dialysis CKD: Longitudinal Study of Patients Receiving Stable Nephrology Care

“…This attitude is supported by our recent study in a similar ND-CKD population showing that risk of ESKD significantly increases by 57% when moderate hyperkalemia associates with non-use of RAASI [18]. Nevertheless, in a recent large survey including 49,571 elderly patients from Canada (58% with eGFR < 60 mL/min/1.73 m 2 ), all with sK ≥ 5.3 mEq/L under RAASI, discontinuation of RAASI was identified as the most frequent antihyperkalemic intervention (74%) [30]. The negative effect of stopping RAASI in HK patients has been recently highlighted by a registry-based study in 9222 patients with heart failure showing that association between HK and mortality risk disappeared after adjustment for RAASI withdrawal: discontinuation of RAASI did associate with 6 to 12-fold greater risk of death while high sK was no longer associated with outcome [31].…”

Stopping RAS Inhibitors in Advanced Chronic Kidney Disease and Cardiorenal Outcomes—Several Unanswered Questions Remain

“…4 Furthermore, in a just-published Canadian population-based retrospective cohort study of RASi discontinuation in 49,571 older adults who developed hyperkalemia, RASi discontinuation was not associated with a higher risk of 1-year cardiovascular events (HR, 0.96; 95% CI, 0.91-1.02) or all-cause mortality (HR, 1.05; 95% CI, 0.96-1.15), compared with no intervention. 5 3…”