Highlights
– A tailored clinical decision support (CDS) tool increased 30‑day reinitiation of ACE inhibitors or ARBs from 13% to 18% among veterans with chronic kidney disease (CKD).
– Absolute improvement was 5% (number needed to treat ~20) over 30 days; most patients still were not reinitiated within that window.
– Patient- and clinician-facing components addressed knowledge gaps, side‑effect management, and referral triggers; generalizability is limited because the cohort was older, predominantly male, and had relatively preserved eGFR.
Background
Renin‑angiotensin system blockers — primarily angiotensin‑converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) — are foundational medications in the management of hypertension, proteinuric chronic kidney disease (CKD), and cardiovascular risk reduction. In randomized trials and observational analyses, these agents slow progression of diabetic and proteinuric nephropathies and reduce cardiovascular events in high‑risk populations (for example, the RENAAL and HOPE trials), and they are embedded in guideline recommendations for many patients with CKD. Despite long-standing evidence and guideline support, ACE inhibitors and ARBs are often underused or discontinued in routine care, in part because of concerns about worsening renal function, hyperkalemia, or adverse symptoms.
Study Design
Sankar D. Navaneethan and colleagues developed a personalized clinical decision support (CDS) tool aimed at primary care providers (PCPs) and tested its impact on reinitiation of ACE inhibitors or ARBs among veterans with CKD who previously had these medications discontinued. Tool development integrated electronic health record (EHR) mining for adverse drug reactions, natural language processing to ascertain documented reasons for discontinuation, and qualitative interviews (15 providers, 10 patients) to identify barriers to (re)starting therapy.
Key CDS components included: a prescriber algorithm for initiation, dosing, uptitration, and reinitiation; patient communication aids to support shared decision‑making; and explicit triggers for nephrology or cardiology consultation.
The intervention was deployed in the Michael E. DeBakey VA Medical Center and VA Tennessee Valley Healthcare System primary care clinics. The study period ran June 2024 to August 2025 and included 1,363 control patients and 1,363 patients exposed to the CDS intervention. Median ages were 76 and 77 years in the intervention and control groups, respectively. The cohort was predominantly male (96% in the decision support group), with about 93% having hypertension and median estimated glomerular filtration rates (eGFRs) of ~44 mL/min/1.73 m2.
The primary outcome was reinitiation of an ACE inhibitor or ARB within 30 days of provider contact.
Key Findings
Within 30 days, 245 of 1,363 patients (18%) in the decision support group had an ACE inhibitor or ARB reinitiated versus 175 of 1,363 (13%) in the control group (P = .001). This represents an absolute increase of 5 percentage points and a relative increase of approximately 38% in the 30‑day reinitiation rate. The implied number needed to treat (NNT) to achieve one additional reinitiation within 30 days is approximately 20.
Beyond the primary outcome, the authors reported that 82% of the decision support group either did not reinitiate or reinitiated after 30 days, versus 87% in the control group. No detailed safety outcomes (e.g., rates of hyperkalemia, acute kidney injury, hospitalizations) were reported in the meeting summary. The study population had a median eGFR in the mid‑40s, and relatively few patients with advanced CKD (eGFR <30 mL/min/1.73 m2) appear to have been included; subgroup data by eGFR strata were not presented in the abstracted summary.
Interpretation and Clinical Significance
The CDS tool produced a statistically significant but clinically modest absolute increase in short‑term reinitiation of ACE inhibitors or ARBs. Several aspects frame the practical significance:
- Magnitude of effect: An absolute 5% increase over 30 days (NNT ~20) is modest; whether this translates into meaningful renal or cardiovascular benefit depends on durability of reinitiation, subsequent adherence, appropriate dosing/uptitration, and avoidance/management of adverse events.
- Patient population: The cohort consisted mainly of older male veterans with median eGFR ≈44; results may not generalize to younger patients, women, non‑veteran populations, or those with more advanced CKD (eGFR <30), where clinician caution about RAAS blockade is often greater.
- Implementation context: The intervention combined automated EHR-derived insights with clinician-facing algorithms and patient communication aids. This hybrid approach likely contributed to the observed effect, but the exact active elements (alerting, algorithm, patient materials, or the combination) are not separated in the reported data.
- Safety and downstream outcomes: The report presented reinitiation as the primary outcome; safety endpoints (hyperkalemia, eGFR changes, hospitalizations) and long‑term renal or cardiovascular outcomes were not reported in the meeting summary and remain important to evaluate in fuller publications.
Why Discontinuation Happens and How the CDS Addressed It
Qualitative work embedded in the study identified principal barriers: clinicians cited uncertainty about kidney‑specific indications, guideline ambiguity in certain scenarios, and lack of confidence managing side effects; patients reported limited understanding of their CKD diagnosis, polypharmacy concerns, and prior side effects. The CDS explicitly targeted these gaps with prescribing algorithms, titration schedules, and patient education templates — elements designed to reduce cognitive friction for PCPs and improve shared decision‑making.
Expert Commentary and Perspective
At the Kidney Week presentation, Navaneethan emphasized the long‑standing underuse of ACE inhibitors and ARBs and suggested that CDS integrated into EHR platforms could facilitate safer reinitiation. Chia‑Ter Chao (not involved in the study) concurred that underutilization is a problem, particularly in advanced CKD, and recommended testing the intervention specifically in patients with eGFR <30 mL/min/1.73 m2, a subgroup where the balance of benefit and risk is less certain and clinician reluctance is higher.
From an implementation science standpoint, the study leverages well‑accepted principles: combine data retrieval (EHR mining), clinician decision algorithms, and patient engagement tools. However, scaling such tools requires attention to alert fatigue, workflow integration, and local practice patterns. Also important is evaluation of whether reinitiation leads to appropriate maintenance and titration to therapeutic doses, and whether monitoring systems are in place to capture and act on adverse events like hyperkalemia.
Limitations
- Population and generalizability: The veteran cohort was overwhelmingly male and older; findings may not extend to community practices, women, or more diverse populations.
- Scope of outcomes: Primary outcome was process‑oriented (medication restart). Clinical outcomes and safety data were not reported in the summary, leaving unanswered questions about net clinical benefit.
- Details of study design: The report does not specify randomization procedures, unit of allocation (patient vs provider vs clinic), blinding, or adjustment for potential confounders — details that will be essential in a full manuscript to assess internal validity.
- Limited representation of advanced CKD: Few patients with eGFR <30 appear to have been included, and the intervention’s safety and efficacy in that higher‑risk group remain uncertain.
- Durability and adherence: The study assessed reinitiation within 30 days; longer follow‑up is required to determine persistence of therapy and subsequent clinical events.
Implications for Practice and Future Research
For clinicians: CDS tools can reduce decision uncertainty and nudge appropriate reinitiation of guideline‑recommended agents, but practices should ensure mechanisms for serum potassium and creatinine monitoring after restarting RAAS blockers and clear plans for dose adjustment or cessation if adverse events occur.
For researchers and health systems: Next steps should include randomized implementation trials with prespecified safety outcomes, analyses stratified by eGFR (including those <30), evaluation of long‑term medication adherence and titration, cost‑effectiveness assessments, and qualitative studies of clinicians who choose not to reinitiate despite CDS prompts.
Conclusion
The reported CDS intervention produced a modest but statistically significant increase in short‑term reinitiation of ACE inhibitors and ARBs among veterans with CKD. The findings support the potential for thoughtfully designed EHR‑embedded tools to influence prescribing behavior. However, the clinical impact will ultimately depend on sustained use, appropriate monitoring for adverse events, and evidence that reinitiation leads to improved renal and cardiovascular outcomes, particularly in patients with more advanced CKD.
Funding and disclosures
The study was supported by a Department of Veterans Affairs Health Service Research & Development Services Investigator‑Initiated Grant (IIR 19‑069). Sankar D. Navaneethan reported relationships with AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, and other companies. Chia‑Ter Chao reported no financial disclosures.
References
1. Brenner BM, Cooper ME, de Zeeuw D, et al.; RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001 Aug 16;345(12):861–869.
2. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G; Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin‑converting‑enzyme inhibitor, ramipril, on cardiovascular events in high‑risk patients. N Engl J Med. 2000 Jan 20;342(3):145–153.
3. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. 2021;100(4S):S1–S87.
AI thumbnail prompt
A busy primary care clinic room with a middle‑aged veteran and a primary care physician looking at an electronic health record screen; the screen displays a clear medication alert to “Consider reinitiating ACE inhibitor/ARB” next to kidney function values and a patient education pamphlet. Natural, clinical lighting; professional, approachable tone; diverse but realistic clinical setting.
