Letter to the Editor: Enhancing renin-angiotensin-aldosterone system inhibitors utilization through patiromer adherence - real-world insights for nephrology practice

Abstract

I read with interest the retrospective cohort study by Kleinman et al published in World Journal of Nephrology. Renin-angiotensin-aldosterone system inhibitors (RAASi) anchor therapy for chronic kidney disease, heart failure, and hypertension, but hyperkalemia often curtails optimal use. This letter synthesizes a retrospective cohort of 13447 patiromer users, where approximately 25% high adherers [proportion of days covered (PDC) ≥ 80%] showed approximately 10% greater RAASi utilization (days’ supply and PDC) across angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and mineralocorticoid receptor antagonists vs lower adherers. Findings echo OPAL-HK, reinforce Kidney Disease: Improving Global Outcomes 2021 binder prioritization, and urge adherence strategies to sustain guideline therapy, cut hospitalizations, and integrate with SGLT2i/finerenone.

Key Words: Renin-angiotensin aldosterone system inhibitors; Patiromer adherence; Hyperkalemia management; Chronic kidney disease; Nephrology practice

Core Tip: Among 13447 real-world patiromer users, high adherence [proportion of days covered (PDC) ≥ 80%] drove approximately 10% higher renin-angiotensin-aldosterone system inhibitors utilization. Prioritize chronic patiromer (Kidney Disease: Improving Global Outcomes 2021/OPAL-HK), monitor PDC, use multidisciplinary support to overcome barriers, and combine with SGLT2i/finerenone for renal/cardiovascular protection.

TO THE EDITOR

Renin-angiotensin-aldosterone system inhibitors (RAASi)-angiotensin-converting enzyme inhibitors (ACEi), angiotensin-receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs)-drive renoprotection and cardioprotection in chronic kidney disease (CKD), heart failure, and hypertension, slashing mortality and progression[1-3]. Yet hyperkalemia disrupts 55%-75% of patients, forcing dose cuts or stops that erode benefits[4-6].

This letter appraises a landmark cohort of 13447 United States patiromer users (2014-2019 claims), where approximately 25% high adherers [6-month proportion of days covered (PDC) ≥ 80%] enabled markedly higher RAASi utilization vs lower adherers-spotlighting adherence as the bridge to guideline-directed care[7].

STUDY DESIGN AND COHORT

I read with great interest the recent article by Kleinman et al[7] published in World Journal of Nephrology. The retrospective analysis used Symphony Health Dataverse claims (commercial/Medicare/Medicaid) for patients starting patiromer 2015-2018, with 6-month pre-/12-month post-index eligibility. Exclusions (< 18 years; prior sodium polystyrene sulfonate) yielded 13447 users (41% female, mean age 62 ± 13 years, 56% medicare)[7].

Adherence stratified by 6-month post-index PDC [≥ 80% high adherers, n = 3323 (25%); < 80% others]. Outcomes focused RAASi metrics (prescriptions, days’ supply, PDC) across classes[7].

STUDY HIGHLIGHTS

Nearly 25% achieved high adherence, yielding approximately 10% superior RAASi utilization-higher days’ supply, PDC, and high-PDC rates-across ACEi, ARBs, and MRAs vs lower adherers (Table 1; all P < 0.01)[7]. Trends included stronger ACEi initiation, confirming adherence unlocks sustained therapy.

Table 1 Renin-angiotensin-aldosterone system inhibitors utilization by patiromer adherence.

RAASi class	Adherent days supply (95%CI)	Lower days supply (95%CI)	Difference (P value)	Adherent PDC (%)	Lower PDC (%)	≥ 80% PDC (adherent vs lower) (%)
ACEi	122.8 (120.0-125.6)	111.2 (109.4-113.1)	11.6 (P < 0.0001)	88.8	84.2	79.2 vs 70.7
ARB	121.2 (118.2-124.3)	111.8 (110.0-113.7)	9.4 (P < 0.0001)	90.9	85.5	77.5 vs 71.5
MRA	114.5 (108.1-121.0)	105.0 (101.2-108.7)	9.6 (P = 0.0122)	87.2	79.1	72.1 vs 62.3

PDC: Proportion of days covered; CI: Confidence interval; ACEi: Angiotensin-converting enzyme inhibitor; ARB: Angiotensin II receptor blocker; MRA: Mineralocorticoid receptor antagonist; RAASi: Renin-angiotensin-aldosterone system inhibitors.

CLINICAL IMPLICATIONS

Real-world trends mirror OPAL-HK: Chronic patiromer sustained RAASi in most hyperkalemic CKD patients, enabling up-titration[8]. They affirm Kidney Disease: Improving Global Outcomes (KDIGO) 2021: Favor binders over RAASi cuts, as maintenance halves hospitalization risk (number needed to treat = 13)[3,9]. Patiromer-sodium-free, outpatient-ready-empowers dosing in comorbid CKD, closing trial-practice gaps[7].

PRACTICE RECOMMENDATIONS

Embed PDC tracking in electronic health records/pharmacy systems with alerts for non-adherers, tying to value-based metrics[10-12]. Multidisciplinary teams address barriers-cost aid, counseling, education-maximizing RAASi benefits in CKD 3-5 with heart failure/diabetes[13].

Limitations and future directions

United States claims limit comorbidity adjustment and global applicability; PDC proxies fills, not intake[9]. Socioeconomics drove disparities; nephrologist/Medicare factors aided adherence[13]. Randomized controlled trials testing patiromer + SGLT2i/finerenone should track estimated glomerular filtration rate, end-stage kidney disease, and major adverse cardiovascular events[7].

CONCLUSION

Adherent patiromer use facilitates optimal RAASi dosing in CKD patients, bridging the gap between clinical trial evidence and real-world practice. Nephrologists should prioritize chronic potassium binder therapy to sustain guideline-directed care and improve outcomes. Future research integrating patiromer with emerging agents promises enhanced nephrology strategies.