Angiotensin II receptor blockers (ARBs)

FMT in HFrEF · Class IAMT in HFpEF · Class IIb

Removal by dialysis

What each drug's prescribing information says about removal by (haemo)dialysis. Where the label is silent, this page says so rather than inferring from protein binding.

CandesartanNot removed (or not meaningfully removed)
- “Candesartan cannot be removed by hemodialysis.”
  ATACAND (candesartan) PI, ANI (2025)· 10 OVERDOSAGE Source
LosartanNot removed (or not meaningfully removed)
- “Neither losartan nor its active metabolite can be removed by hemodialysis.”
  COZAAR (losartan potassium) tablets, prescribing information, Organon LLC (2026)· 10 OVERDOSAGE Source
ValsartanNot removed (or not meaningfully removed)
- “Diovan (valsartan) is not removed from the plasma by hemodialysis.”
  DIOVAN (valsartan) PI, Novartis (2026)· 10 OVERDOSAGE Source

After starting: what a change in creatinine, eGFR or potassium means

Some rise in urea, creatinine and potassium is expected. An eGFR fall of less than 30% and potassium up to 5.5 mmol/L are acceptable. Larger rises: stop nephrotoxins and potassium-retaining drugs, reduce the diuretic if not congested; if they persist, halve the dose and re-check within 1–2 weeks. Stop and seek advice if potassium exceeds 5.5 mmol/L, creatinine more than doubles, or eGFR falls below 20.

“Some rise in urea (BUN), creatinine, and potassium is to be expected after an ACE-I; if an increase is small, no action is necessary.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 Source
“A decrease in eGFR of <30% is acceptable.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 Source
“An increase in potassium to ≤5.5 mmol/L is acceptable.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 Source
“If greater rises in creatinine or potassium than those outlined above persist despite adjustment of concomitant medications, the dose of the ACE-I (or ARB) should be halved and blood chemistry rechecked within 1–2 weeks; if there is still an unsatisfactory response, specialist advice should be sought.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 12, Table S4 Source
“If potassium rises to >5.5 mmol/L or creatinine increases by >100% or to eGFR <20 mL/min/1.73 m2, the ACE-I (or ARB) should be stopped and specialist advice sought.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 12, Table S4 Source

A hemodynamic eGFR dip of up to 30% after starting an SGLT2 inhibitor, RAAS inhibitor, MRA or ARNI is expected and should not lead to discontinuation; above 30%, look for other causes of AKI (KDIGO). ESC accepts a creatinine rise of less than 50% above baseline as long as eGFR stays above 15.

“Hemodynamic fluctuations in eGFR up to 30% can be seen and should not lead to discontinuation”
Lam CSP, Bozkurt B, Cherney DZI, et al. Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Conclusions From a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. JACC: Heart Failure 2026 (KDIGO Executive Conclusions) (2026)· p. 10
“If >30%, other causes of AKI should be evaluated”
Lam CSP, Bozkurt B, Cherney DZI, et al. Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Conclusions From a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. JACC: Heart Failure 2026 (KDIGO Executive Conclusions) (2026)· p. 10
“An increase in serum creatinine of <50% above baseline, as long as eGFR remains >15 mL/min/1.73 m2, is considered acceptable.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 66, Section 10.3 Source
“Worsening kidney function alone is not an independent determinant of outcomes in patients with acute HF.”
Lam CSP, Bozkurt B, Cherney DZI, et al. Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Conclusions From a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. JACC: Heart Failure 2026 (KDIGO Executive Conclusions) (2026)· p. 11

Drugs and doses

Drug	Brands	Start	Target	Kidney dosing
Candesartan	Atacand	4 mg o.d. (AHA 2022 / ACC 2024: 4-8 mg o.d.)	32 mg o.d.	FDA: no initial dose adjustment for renal insufficiency; exposure ~doubled when CrCl <30 and similar on haemodialysis; not removed by haemodialysis. US HF indication: NYHA II-IV, LVEF <=40% (CHARM excluded serum creatinine >3 mg/dL and K >5.5 mEq/L).
Losartan	Cozaar	(12.5) 25-50 mg o.d.	150 mg o.d. (HEAAL; above the US label maximum of 100 mg/day)	FDA: no dose adjustment in renal impairment unless also volume depleted (then start 25 mg); exposure up 50-90% in mild-moderate renal insufficiency; neither losartan nor its active metabolite is removed by haemodialysis. NO US heart-failure indication (HF use is off-label; ESC/ACC/AHA list it).
Valsartan	Diovan	40 mg b.i.d.	160 mg b.i.d.	FDA: no dose adjustment for GFR 30-90; safety and effectiveness not established for GFR <30; no correlation between CrCl and exposure down to CrCl 10 mL/min; not removed by haemodialysis. US HF indication is to reduce HF hospitalization only (no added benefit on top of an adequate ACE-I dose).

Status by kidney stage

Stage	Initiate	Continue
G1	Recommended Class I FMT alternative in HFrEF when ACE-I and ARNI are not tolerated; candesartan and valsartan carry US HF indications; no renal restriction.	Recommended Continue at highest tolerated dose; routine K+/creatinine monitoring.
G2	Recommended As G1; FDA valsartan label: no dose adjustment for GFR 60-90.	Recommended Continue; monitor renal function and potassium periodically.
G3a	Recommended ESC CVD-CKD Class I for eGFR >=30; no label dose adjustment for moderate renal impairment (losartan exposure 50-90% higher, no adjustment).	Recommended Continue; an initial creatinine rise is expected and is not a reason to stop.
G3b	Recommended Still covered by the ESC CVD-CKD Class I recommendation (eGFR >=30); ESC CVD-CKD suggests a more cautious titration below eGFR ~40.	Recommended Continue despite an eGFR dip; titrate cautiously given limited kidney reserve.
G4	Use with caution May be considered (ESC CVD-CKD Class IIb, C) at low dose with slow titration and close K+/eGFR monitoring; ESC HF Table S4 lists eGFR <30 as 'caution/seek specialist advice'; valsartan label: safety not established below GFR 30.	Use with caution Continue under close monitoring (KDIGO: continue even when eGFR falls below 30); stop if eGFR falls to <20 or creatinine rises >100% (ESC Table S4).
G5	Not recommended No HF data below eGFR 15 (ESC CVD-CKD); ESC HF advises temporary discontinuation may be needed at eGFR <15 and Table S4 stops ACE-I/ARB if eGFR falls <20; do not start outside specialist care (conservative choice).	Use with caution Individualize: KDIGO supports continuing (STOP-ACEi showed no benefit of stopping at mean eGFR 13) but allows dose reduction/withdrawal for uraemic symptoms, hyperkalaemia or hypotension; ESC HF: temporary discontinuation may be needed.
dialysis	Use with caution Not contraindicated by any label; candesartan/losartan/valsartan are not removed by haemodialysis and need no label dose change, but ESC CVD-CKD states there are no data supporting HFrEF use on dialysis and KDIGO 2026 calls G5D a knowledge gap; small dialysis RCTs (telmisartan in HFrEF on HD; candesartan; mixed ARBs) were positive, OCTOPUS (olmesartan) neutral. Nephrology/HF specialist decision; watch intradialytic hypotension and hyperkalaemia.	Use with caution Continuation reasonable if BP and potassium allow; individualize with nephrology.
aki	Not recommended Do not start during AKI; initiate only in stable patients after recovery (ESC Table S4: in hospital after stabilizing).	Use with caution Consider withholding (labels; ESC HF) when AKI is clinically significant: stop if creatinine rises >100%, eGFR falls <20 or K >5.5 (ESC Table S4); halve dose for smaller excess rises; a rise <50% with eGFR >15 is acceptable (ESC HF). Restart when renal function recovers (2-4 weeks; within 14 days restart at prior dose).
transplant	Allowed No HF-specific transplant data; KDIGO 2021 BP recommends an ARB (or dihydropyridine CCB) as first-line antihypertensive in kidney transplant recipients; apply the eGFR rules of the graft and involve the transplant team.	Allowed Continue per graft eGFR and potassium; coordinate with transplant team (drug interactions, hyperkalaemia with calcineurin inhibitors).

Cutoffs recorded from the sources

potassium > 5.2 mmol/L → caution (initiate; candesartan, losartan, valsartan)
“Significant hyperkalaemia (K+ >5.2 mmol/L).” — esc2026-supp, p. 10, Table S4 (Cautions/seek specialist advice)
potassium >= 5 mmol/L → not-recommended (initiate; candesartan, losartan, valsartan)
“In patients with eGFR <60 ml/min per 1.73 m2, initiate ACEi, ARB, sMRA, or nsMRA if serum potassium is <5 mEq/l.” — kdigo2026-hf, p. 11, Figure 4
egfr < 30 mL/min/1.73m2 → caution (initiate; candesartan, losartan, valsartan)
“Significant renal dysfunction (eGFR <30 mL/min/1.73 m2). May be considered in lower eGFR under close monitoring of eGFR after initiation.” — esc2026-supp, p. 10, Table S4 (Cautions/seek specialist advice)
egfr < 30 mL/min/1.73m2 → caution (initiate; valsartan)
“Safety and effectiveness of Diovan in patients with severe renal impairment (glomerular filtration rate less than 30 mL/min/1.73 m2) have not been established.” — fda-valsartan, Section 8.6 Renal Impairment
egfr < 15 mL/min/1.73m2 → not-recommended (initiate; candesartan, losartan, valsartan)
“There are no data to support the use of these agents in patients with HFrEF with kidney failure (eGFR <15 mL/min/1.73 m2 or dialysis).” — esc2026-ckd, p. 36, Section 6.2.2.1.1
egfr < 40 mL/min/1.73m2 → caution (uptitrate; candesartan, losartan, valsartan)
“A more cautious approach could be applied in patients with moderate or severe CKD (e.g. eGFR <40 mL/min/1.73 m2) given limited kidney reserve.” — esc2026-ckd, p. 44, Section 6.4
sbp < 90 mmHg → caution (initiate; candesartan, losartan, valsartan)
“Symptomatic or severe asymptomatic hypotension (systolic blood pressure <90 mmHg).” — esc2026-supp, p. 10, Table S4 (Cautions/seek specialist advice)
creatinine_abs >= 2.5 mg/dL → caution (initiate; candesartan, losartan, valsartan)
“ACEi or ARB All persons with CKD, and moderate or severe albuminuria in persons with and without diabetes Should be continued in CKD even when eGFR declines to <30 ml/min per 1.73 m2 Serum creatinine <221 mmol/l (<2.5 mg/dl) or eGFR > 30 ml/min per 1.73 m2” — kdigo2026-hf, p. 10, Table 2
creatinine_abs > 3 mg/dL → caution (initiate; candesartan)
“Patients with serum creatinine > 3 mg/dL, serum potassium > 5.5 mEq/L, symptomatic hypotension or known bilateral renal artery stenosis were excluded.” — fda-candesartan, Section 14.2 Heart Failure
other < 30 % decrease in eGFR → allowed (continue; candesartan, losartan, valsartan)
“A decrease in eGFR of <30% is acceptable.” — esc2026-supp, p. 11, Table S4 (Problem solving)
creatinine_rise_pct < 50 % above baseline → allowed (continue; candesartan, losartan, valsartan)
“An increase in serum creatinine of <50% above baseline, as long as eGFR remains >15 mL/min/1.73 m2, is considered acceptable.” — esc2026, p. 66, Section 10.3
creatinine_rise_pct > 100 % above baseline → not-recommended (hold; candesartan, losartan, valsartan)
“If potassium rises to >5.5 mmol/L or creatinine increases by >100% or to eGFR <20 mL/min/1.73 m2, the ACE-I (or ARB) should be stopped and specialist advice sought.” — esc2026-supp, p. 12, Table S4 (Problem solving)
egfr < 20 mL/min/1.73m2 → not-recommended (hold; candesartan, losartan, valsartan)
“If potassium rises to >5.5 mmol/L or creatinine increases by >100% or to eGFR <20 mL/min/1.73 m2, the ACE-I (or ARB) should be stopped and specialist advice sought.” — esc2026-supp, p. 12, Table S4 (Problem solving)
potassium > 5.5 mmol/L → not-recommended (hold; candesartan, losartan, valsartan)
“If potassium rises to >5.5 mmol/L or creatinine increases by >100% or to eGFR <20 mL/min/1.73 m2, the ACE-I (or ARB) should be stopped and specialist advice sought.” — esc2026-supp, p. 12, Table S4 (Problem solving)
potassium <= 5.5 mmol/L → allowed (continue; candesartan, losartan, valsartan)
“An increase in potassium to ≤5.5 mmol/L is acceptable.” — esc2026-supp, p. 11, Table S4 (Problem solving)
potassium > 5.5 mmol/L → caution (dose_reduce; candesartan, losartan, valsartan)
“Severe hyperkalaemia (potassium >5.5 or >6 mmol/L) should lead to temporary down-titration or discontinuation of MRAs and/or ARNIs/ACE-Is/ARBs (see Supplementary data online, Tables S4, S5 and S9).” — esc2026, p. 35, Section 6.1.6
potassium > 6 mEq/L → not-recommended (hold; candesartan, losartan, valsartan)
“Generally, dose reduction of these agents is advised if potassium is between 5.5 mEq/L and 6 mEq/L and temporarily termination if potassium is above 6 mEq/L, with reinstitution of the drug only when the potassium drops below 5.5 mEq/L.” — mullens2022, p. 13
creatinine_rise_pct > 50 % above baseline → not-recommended (hold; candesartan, losartan, valsartan)
“In contrast, only if serum creatinine rises by >50% or above 3.5 mg/dl treatment should be discontinued with re-challenge when possible” — mullens2022, p. 13
creatinine_abs > 3.5 mg/dL → not-recommended (hold; candesartan, losartan, valsartan)
“In contrast, only if serum creatinine rises by >50% or above 3.5 mg/dl treatment should be discontinued with re-challenge when possible” — mullens2022, p. 13
creatinine_rise_pct > 30 % within 4 weeks of start/dose increase → caution (continue; candesartan, losartan, valsartan)
“Practice Point 3.6.4: Continue ACEi or ARB therapy unless serum creatinine rises by more than 30% within 4 weeks following initiation of treatment or an increase in dose.” — kdigo2024-ckd, p. 44, Summary of recommendations, Practice Point 3.6.4 (also p. 98)
egfr < 15 mL/min/1.73m2 → caution (continue; candesartan, losartan, valsartan)
“However, temporary discontinuation of MRAs/ARNIs/ACE-Is/ARBs and SGLT2-Is may be needed in cases with acute kidney injury and eGFR <15 mL/min/1.73 m2.” — esc2026, p. 35, Section 6.1.6
creatinine_rise_pct > 50 % above baseline (decompensated HF) → caution (hold; candesartan, losartan, valsartan)
“CAUTION IN CASE OF >50% increase in serum creatinine or absolute serum creatinine increases above >300 μmol/L” — esc2026-ckd, p. 45, Figure 12

Trial evidence (informational)

CHARM-Alternative · HFrEF (LVEF <=40%), ACE-I intolerant; serum creatinine >3 mg/dL excluded
CV death or HF hospitalization: HR 0.77 (95% CI 0.67-0.89); covariate adjusted 0.70 (0.60-0.81)
“During a median follow-up of 33.7 months, 334 (33%) of 1013 patients in the candesartan group and 406 (40%) of 1015 in the placebo group had cardiovascular death or hospital admission for CHF (unadjusted hazard ratio 0.77 [95% CI 0.67-0.89], p=0.0004; covariate adjusted 0.70 [0.60-0.81], p<0.0001).” — granger2003, Abstract (Findings)
CHARM-Added · HFrEF (LVEF <=40%) on an ACE inhibitor
CV death or HF hospitalization: 15% relative risk reduction (HR 0.85, 95% CI 0.75-0.96)
“After a median follow-up of 41 months, there was a 15% reduction in the risk of cardiovascular death or heart failure hospitalization on ATACAND (p=0.011), with both components contributing to the overall effect (Table 2).” — fda-candesartan, Section 14.2 Heart Failure
HEAAL · HFrEF (LVEF <=40%), ACE-I intolerant; losartan 150 vs 50 mg
Death or HF admission: HR 0.90 (95% CI 0.82-0.99)
“With 4.7-year median follow-up in each group (IQR 3.7-5.5 for losartan 150 mg; 3.4-5.5 for losartan 50 mg), 828 (43%) patients in the 150 mg group versus 889 (46%) in the 50 mg group died or were admitted for heart failure (hazard ratio [HR] 0.90, 95% CI 0.82-0.99; p=0.027).” — konstam2009, Abstract (Findings)
HEAAL (safety) · as above
Renal impairment, hypotension, hyperkalaemia: More frequent with 150 mg than 50 mg, without more discontinuations
“Renal impairment (n=454 vs 317), hypotension (203 vs 145), and hyperkalaemia (195 vs 131) were more common in the 150 mg group than in the 50 mg group, but these adverse events did not lead to significantly more treatment discontinuations in the 150 mg group.” — konstam2009, Abstract (Findings)
Val-HeFT · HF NYHA II-IV, LVEF <40%, ~93% on ACE-I
Combined mortality and morbidity: RR 0.87 (97.5% CI 0.77-0.97); no mortality effect
“The incidence of the combined end point, however, was 13.2 percent lower with valsartan than with placebo (relative risk, 0.87; 97.5 percent confidence interval, 0.77 to 0.97; P=0.009), predominantly because of a lower number of patients hospitalized for heart failure; 455 (18.2 percent) in the placebo group and 346 (13.8 percent) in the valsartan group (P<0.001).” — cohn2001, Abstract (Results)
Val-HeFT (no ACE-I subgroup) · Val-HeFT patients not on an ACE inhibitor (n=366)
HF morbidity: HR 0.51 (95% CI 0.35-0.73); little benefit when added to adequate ACE-I
“Thus, there is little evidence of further clinical benefit when valsartan is added to an adequate dose of ACE inhibitor.” — fda-valsartan, Section 14.2 Heart Failure
CHARM-Preserved · HF with LVEF >40%
CV death or HF admission: HR 0.89 (95% CI 0.77-1.03), not significant; fewer HF admissions
“333 (22%) patients in the candesartan and 366 (24%) in the placebo group experienced the primary outcome (unadjusted hazard ratio 0.89 [95% CI 0.77-1.03], p=0.118; covariate adjusted 0.86 [0.74-1.0], p=0.051).” — yusuf2003, Abstract (Findings)
ARB meta-analysis in HFpEF (4 trials) · HFpEF
CV death, all-cause death, HFH: No signal for benefit (HFH HR 0.92, 95% CI 0.83-1.02)
“In a meta-analysis of four trials evaluating ARBs in patients with HFpEF, there was no signal for benefit on CV death (HR 1.02), all-cause death (HR 1.01; 95% CI 0.92–1.11), or HFH (HR 0.92; 95% CI 0.83–1.02).” — esc2026, p. 36, Section 6.1.7.1
ESC 2026 overall assessment · HFrEF
All-cause mortality: No ARB has reduced all-cause mortality
“However, no ARB has reduced all-cause mortality in any trial, and combination with an ACE-I increases adverse effects.” — esc2026, p. 33, Section 6.1.4.2
Cice 2010 (telmisartan, not an ESC-listed ARB) · Haemodialysis patients with HFrEF (LVEF <=40%) on ACE-I
All-cause mortality: HR 0.51 (95% CI 0.32-0.82)
“With Cox proportional hazards analysis, telmisartan was an independent determinant of all-cause mortality (hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.32 to 0.82; p < 0.01), cardiovascular mortality (HR: 0.42; 95% CI: 0.38 to 0.61; p < 0.0001), and hospital stay for deterioration of heart failure (HR: 0.38; 95% CI: 0.19 to 0.51; p < 0.0001).” — cice2010, Abstract (Results)

Acute kidney injury

Do not initiate during AKI. For an ARB already prescribed: a creatinine rise <50% (eGFR >15) or eGFR fall <30% is acceptable and should not prompt interruption (ESC); with excessive rises first stop nephrotoxins/K-retaining drugs and reduce diuretic if not congested, then halve the ARB; stop if K >5.5, creatinine >100% rise or eGFR <20 (ESC Table S4), or consider withholding for any clinically significant decrease in renal function (all three FDA labels). ESC HF: temporary discontinuation may be needed with AKI and eGFR <15. Sick-day/peri-procedural holds are optional (KDIGO 2024, ESC CVD-CKD) with an explicit restart plan. Rechallenge after 2-4 weeks once renal function recovers (Beldhuis); if interrupted <14 days, restart at the prior dose in stable patients (ESC).

“Thus, a transient decrease in kidney function after the initiation of ACE-Is/ARNIs/ARBs and MRAs or SGLT2-Is should not prompt their interruption.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 66, Section 10.3 Source
“If urea, creatinine, or potassium does rise excessively, consider stopping concomitant nephrotoxic drugs (e.g. NSAIDsc) and other potassium supplements or retaining agents (triamterene, amiloride) and, if no signs of congestion, reducing the dose of diuretic.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 (Problem solving) Source
“If greater rises in creatinine or potassium than those outlined above persist despite adjustment of concomitant medications, the dose of the ACE-I (or ARB) should be halved and blood chemistry rechecked within 1–2 weeks; if there is still an unsatisfactory response, specialist advice should be sought.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 12, Table S4 (Problem solving) Source
“Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on COZAAR [see Drug Interactions (7.3) and Use in Specific Populations (8.7)].”
COZAAR (losartan potassium) tablets, prescribing information, Organon LLC (2026)· Warnings and Precautions 5.3 Source
“Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Diovan [see Drug Interactions (7)].”
DIOVAN (valsartan) PI, Novartis (2026)· Warnings and Precautions 5.3 Source
“After possible (temporary) downtitration or even discontinuation, a rechallenge should be considered when renal function (and potassium) has recovered after 2 to 4 weeks.”
Beldhuis 2022 Circulation: Evidence-based medical therapy in HFrEF patients with CKD (2022)· p. 4 Source
“In the context of uptitration of ARBs some increase in serum creatinine / drop in eGFR is expected and acceptable.”
Beldhuis 2022 Circulation: Evidence-based medical therapy in HFrEF patients with CKD (2022)· p. 6, Figure 2B (ARB panel) Source
“Although not supported by any strong evidence, patients may be counselled to withhold ACEI/ARBs, SGLT2 inhibitors, non-steroidal MRAs, and GLP-1RAs temporarily if not able to maintain oral intake (‘sick day rules’).”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 31, Section 5.5 Source
“However, there is a paucity of evidence to support sick day rules to prevent AKI or other clinically relevant outcomes.”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 136, Section 4.3 Source
“If FMT has been temporarily discontinued for less than 14 days, it should, in most cases, be safe to initiate FMT directly at the previously tolerated doses in stable patients.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 35, Section 6.1.6 Source
“Patients whose renal function may depend, in part, on the activity of the renin-angiotensin system (e.g., patient with renal artery stenosis, chronic kidney disease, severe heart failure, or volume depletion) may be at particular risk of developing oliguria, progressive azotemia or acute renal failure when treated with ATACAND.”
ATACAND (candesartan) PI, ANI (2025)· Warnings and Precautions 5.4 Source

Dialysis

No ARB has an HF trial in dialysis among the ESC-listed agents. Labels: none is removed by haemodialysis; candesartan exposure on haemodialysis is similar to severe renal impairment; losartan/valsartan need no label dose change (valsartan: no exposure-CrCl correlation down to CrCl 10, but safety not established <30). ESC CVD-CKD: no data supporting HFrEF use with eGFR <15 or dialysis; KDIGO 2026 HF: G5D efficacy/safety a knowledge gap. Small RCTs: telmisartan added to ACE-I in HD patients with HFrEF (Cice 2010, n=332) reduced death and HF admissions; candesartan in HD without cardiac disease (Takahashi 2006, n=80) and mixed ARBs incl. candesartan/losartan/valsartan in HD (Suzuki 2008, open label, n=360) reduced CV events; olmesartan (OCTOPUS 2013, n=469, hypertensive HD) was neutral. Proposed status: caution (specialist, individualized); hypotension on dialysis days and hyperkalaemia are the main limits.

Trials: Cice 2010 (telmisartan in HD with HFrEF), Takahashi 2006 (candesartan in HD)

“Neither losartan nor its active metabolite can be removed by hemodialysis.”
COZAAR (losartan potassium) tablets, prescribing information, Organon LLC (2026)· Section 10 Overdosage Source
“There is no apparent correlation between renal function (measured by creatinine clearance) and exposure (measured by AUC) to valsartan in patients with different degrees of renal impairment (down to creatinine clearance of 10 mL/min).”
DIOVAN (valsartan) PI, Novartis (2026)· Section 12.3 Pharmacokinetics (Renal Insufficiency) Source
“Diovan (valsartan) is not removed from the plasma by hemodialysis.”
DIOVAN (valsartan) PI, Novartis (2026)· Section 10 Overdosage Source
“Symptomatic hypotension is most likely to occur in patients who have been volume and/or salt depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting.”
ATACAND (candesartan) PI, ANI (2025)· Warnings and Precautions 5.3 Source
“There are no data to support the use of these agents in patients with HFrEF with kidney failure (eGFR <15 mL/min/1.73 m2 or dialysis).”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 36, Section 6.2.2.1.1 Source
“However, in CKD G5D, the efﬁcacy and safety of GDMT remain knowledge gaps.”
Lam CSP, Bozkurt B, Cherney DZI, et al. Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Conclusions From a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. JACC: Heart Failure 2026 (KDIGO Executive Conclusions) (2026)· p. 9
“In CKD stage 5, the KDIGO guidelines still indicate the use of ACE-I and ARBs with moderate evidence for ACE-I/ARB if CKD stage 5 and dialysis and weak evidence supporting their use in patients with CKD stage 5 not on dialysis.”
Mullens 2022 EJHF: Renal effects of GDMT in HF, HFA/ESC consensus statement (2022)· p. 6 Source
“RESULTS: at 3 years, telmisartan significantly reduced all-cause mortality (35.1% vs. 54.4%; p < 0.001), cardiovascular death (30.3% vs. 43.7%; p < 0.001), and hospital admission for CHF (33.9% vs. 55.1%; p < 0.0001).”
Cice G et al. Telmisartan added to ACE inhibitors in hemodialysis patients with CHF. J Am Coll Cardiol 2010 (PMID 21070920, abstract) (2010)· Abstract (Results) Source
“CONCLUSIONS: Candesartan therapy significantly reduces cardiovascular events and mortality in patients on chronic maintenance haemodialysis and therefore improves the prognosis of these patients.”
Takahashi A et al. Candesartan reduces cardiovascular events in chronic haemodialysis. Nephrol Dial Transplant 2006 (PMID 16766543, abstract) (2006)· Abstract (Conclusions) Source
“After adjustment for age, sex, diabetes, systolic blood pressure, and center, treatment with an ARB was independently associated with reduced fatal and nonfatal CVD events (hazard ratio, 0.51; 95% confidence interval, 0.33 to 0.79; P = 0.002).”
Suzuki H, et al. Effect of angiotensin receptor blockers on cardiovascular events in patients undergoing hemodialysis: an open-label randomized controlled trial. Am J Kidney Dis 2008;52:501-6 (PubMed abstract, PMID 18653268) (2008)· Abstract (Results) Source
“CONCLUSIONS: BP-lowering treatment with an ARB did not significantly lower the risks of major cardiovascular events or death among patients with hypertension on chronic HD.”
Iseki K, et al. (OCTOPUS) Effects of ARB on mortality and cardiovascular outcomes in patients with long-term haemodialysis: a randomized controlled trial. Nephrol Dial Transplant 2013;28:1579-89 (PubMed abstract, PMID 23355629) (2013)· Abstract (Conclusions) Source
“Safety and effectiveness of Diovan in patients with severe renal impairment (glomerular filtration rate less than 30 mL/min/1.73 m2) have not been established.”
DIOVAN (valsartan) PI, Novartis (2026)· Section 8.6 Source
“The pharmacokinetics of candesartan in hypertensive patients undergoing hemodialysis are similar to those in hypertensive patients with severe renal impairment. Candesartan cannot be removed by hemodialysis.”
ATACAND (candesartan) PI, ANI (2025)· Section 12.3 Source

Kidney transplant

No HF-specific data for ARBs in kidney transplant recipients. KDIGO 2021 BP guideline recommends an ARB or dihydropyridine CCB as first-line antihypertensive in adult kidney transplant recipients (1C); ESC CVD-CKD favours CCBs for BP after transplant (no hyperkalaemia) and advises involving the transplant team before new drugs. Treat by graft eGFR stage with the same K+/creatinine rules.

“Recommendation 4.1: We recommend that a dihydropyridine calcium channel blocker (CCB) or an ARB be used as the ﬁrst-line antihypertensive agent in adult kidney transplant recipients (1C).”
KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in CKD (2021)· p. 30, Recommendation 4.1 Source
“When initiating new treatment, consultation with the patient’s transplant team is advisable to ensure that there are no important considerations for the graft, and particularly relevant drug interactions.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 72, Section 13.2.2 Source
“In the early posttransplant period, ARBs should be avoided until kidney transplant function stabilizes, as the acute negative effect of an ARB on GFR can be confused with other causes of graft dysfunction (e.g., rejection).”
KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in CKD (2021)· p. 62, Recommendation 4.1 rationale Source

Albuminuria

Albuminuria strengthens the CKD indication for RAS blockade (KDIGO 2024: recommended for A3 without diabetes and A2-A3 with diabetes, G1-G4; ESC CVD-CKD: ACEI/ARB for most CKD, optional only without albuminuria and with normal/low BP and no HF). Losartan has a US label indication for diabetic nephropathy with UACR >=300 mg/g. For HFrEF the ARB indication does not depend on albuminuria.

“Recommendation 3.6.3: We recommend starting RASi (ACEi or ARB) for people with CKD and moderately-to-severely increased albuminuria (G1–G4, A2 and A3) with diabetes (1B).”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 43, Summary of recommendations, Recommendation 3.6.3 (also p. 98) Source
“Practice Point 3.6.6: Consider starting people with CKD with normal to mildly increased albuminuria (A1) on RASi (ACEi or ARB) for speciﬁc indications (e.g., to treat hypertension or heart failure with low ejection fraction).”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 44, Summary of recommendations, Practice Point 3.6.6 (also p. 98) Source
“Angiotensin-converting enzyme inhibitors or ARBs are recommended for most patients with CKD. One might consider not prescribing an ACEI/ARB in patients with normal/low blood pressure without albuminuria (unless there is another indication for use).”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 28, Section 5.5 Source
“COZAAR is indicated for the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (urinary albumin to creatinine ratio ≥300 mg/g) in patients with type 2 diabetes and a history of hypertension.”
COZAAR (losartan potassium) tablets, prescribing information, Organon LLC (2026)· Section 1.3 Nephropathy in Type 2 Diabetic Patients Source

Monitoring

Check renal function and electrolytes before starting; recheck urea/creatinine/K+ 1-2 weeks after initiation and 1-2 weeks after the final titration, then every 4-6 months (ESC Table S4); KDIGO CKD guidance: within 2-4 weeks (ESC CVD-CKD key message: 1-4 weeks). Monitor more often in CKD G4-G5 and when combined with MRA or other K-raising drugs. Avoid ACE-I + ARB (+ MRA triple) combinations and NSAIDs.

“Recheck blood chemistry (urea/BUN, creatinine, K+) 1–2 weeks after initiation and 1–2 weeks after final dose titration.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 (How to use?) Source
“Monitor blood chemistry 4–6 monthly thereafter.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 (How to use?) Source
“Practice Point 3.6.2: Changes in BP, serum creatinine, and serum potassium should be checked within 2–4 weeks of initiation or increase in the dose of a RASi, depending on the current GFR and serum potassium.”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 44, Summary of recommendations, Practice Point 3.6.2 (also p. 98) Source
“Extra biochemical monitoring after initiation of SGLT2 inhibitors or GLP-1RAs is not routinely required, but 1–4 weeks after initiation of RAAS blockade serum potassium and eGFR should be re-checked”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 75, Section 15/16 key messages Source
“In the ACE-I/ARB/ARNI and SGLT2 inhibitor trials, laboratory assessment of creatinine, urea, eGFR and electrolytes was typically done after 14 days during drug titration and every 4 months thereafter.”
Mullens 2022 EJHF: Renal effects of GDMT in HF, HFA/ESC consensus statement (2022)· p. 14 Source
“Monitor serum potassium periodically.”
ATACAND (candesartan) PI, ANI (2025)· Warnings and Precautions 5.5 Source
“Triple combination of ATACAND with an ACE-inhibitor and a mineralocorticoid receptor antagonist is generally not recommended.”
ATACAND (candesartan) PI, ANI (2025)· Drug Interactions 7.4 Source
“Combined use of an ARB with an ACEI is not recommended in patients with CKD as the risk of AKI and severe hyperkalaemia outweighs any added cardiorenal benefits.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 31, Recommendation Table 12 (Class III) Source
“Some patients with heart failure have developed increases in potassium. These effects are usually minor and transient, and they are more likely to occur in patients with pre-existing renal impairment.”
DIOVAN (valsartan) PI, Novartis (2026)· Warnings and Precautions 5.4 Source

In-hospital initiation

Continue (or rapidly reintroduce) an ARB already taken during decompensation unless hypoperfusion, severe haemodynamic instability, or a specific indication; a mild creatinine rise or asymptomatic BP fall is not a reason to stop. New starts after stabilization, ideally before discharge; rapid in-hospital uptitration is acceptable with close monitoring.

“In patients already receiving FMT, continuation and/or rapid reintroduction as soon as possible is recommended. Discontinuation of FMT is not recommended unless there are clear signs of hypoperfusion or specific clinical indications.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 45, Section 7.4.1 Source
“In patients hospitalized with DHF—after stabilizing (but ideally before discharge).”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 (Where?) Source
“In patients experiencing mild decrease of renal function or asymptomatic reduction of blood pressure during HF hospitalization, diuresis and other GDMT should not routinely be discontinued (6-11).”
2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure (2022)· p. 80, Section 8 recommendation 2 Source
“Temporary discontinuation of beta-blockers and ARNIs/ACE-Is/ARBs is advised in patients with severe haemodynamic instability.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 35, Section 6.1.6 Source

Outpatient

Start in stable outpatients (refer NYHA IV/advanced HF/recent exacerbation to specialist); double the dose at intervals of not less than 2 weeks if close monitoring is not possible (candesartan label: doubling about every 2 weeks); aim for target or highest tolerated dose.

“In the community in stable patients (NYHA class IV/patients with advanced HF and those with a current/recent exacerbation should be referred for specialist advice).”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 (Where?) Source
“In those patients where close monitoring is not possible, dose should be doubled at not less than 2-week intervals.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 (How to use?) Source
“It is very rarely necessary to stop an ACE-I (or ARB), and clinical deterioration is likely if treatment is withdrawn.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 (How to use?) Source

Where sources disagree

Initiation at eGFR 15-29 (CKD G4)

“Treatment with an ACEI or ARB may be considered in patients with HFrEF and CKD with an eGFR 15–29 mL/min/1.73 m2 to reduce the risk of HF hospitalization and cardiovascular death.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 39, Recommendation Table 15 (Class IIb, C) Source
“Significant renal dysfunction (eGFR <30 mL/min/1.73 m2). May be considered in lower eGFR under close monitoring of eGFR after initiation.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 10, Table S4 Source
“Safety and effectiveness of Diovan in patients with severe renal impairment (glomerular filtration rate less than 30 mL/min/1.73 m2) have not been established.”
DIOVAN (valsartan) PI, Novartis (2026)· Section 8.6 Renal Impairment Source
“<15 15–29 30–59 ≥60 • ß-blocker • Hydralazine/ nitrates • ß-blocker • SGLT2i if eGFR >20 • Vericiguat • ß-blocker • ARNI, ACEi, or ARB”
Lam CSP, Bozkurt B, Cherney DZI, et al. Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Conclusions From a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. JACC: Heart Failure 2026 (KDIGO Executive Conclusions) (2026)· p. 11, Figure 4 (HFrEF columns <15, 15–29, 30–59, ≥60)
“We are aligned with KDIGO guideline recommendation to use ACE-I/ARB also in more advanced CKD stages (stage 4–5).”
Mullens 2022 EJHF: Renal effects of GDMT in HF, HFA/ESC consensus statement (2022)· p. 6 Source

Tool uses esc2026-ckd: No FDA contraindication; candesartan/losartan labels need no renal dose change and the valsartan label only says 'not established'. ESC CVD-CKD 2026 (IIb) and ESC HF Table S4 both permit use with close monitoring, so status = caution. KDIGO 2026 Figure 4 (HFrEF 15-29 column lists only beta-blocker, SGLT2i, vericiguat) is the most restrictive; flag for owner.

Continuation as eGFR falls below 30 / below 20 / below 15

“Practice Point 3.6.7: Continue ACEi or ARB in people with CKD even when the eGFR falls below 30 ml/min per 1.73 m2.”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 44, Summary of recommendations, Practice Point 3.6.7 (also p. 98) Source
“If potassium rises to >5.5 mmol/L or creatinine increases by >100% or to eGFR <20 mL/min/1.73 m2, the ACE-I (or ARB) should be stopped and specialist advice sought.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 12, Table S4 Source
“An increase in serum creatinine of <50% above baseline, as long as eGFR remains >15 mL/min/1.73 m2, is considered acceptable.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 66, Section 10.3 Source
“With potassium monitoring, ACEI/ARBs can safely be continued as kidney function declines to severe CKD and kidney failure to manage blood pressure and cardiovascular risk.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 28, Section 5.5 Source

Tool uses esc2026-supp: ESC 2026 HF guidance (Table S4) is HF-specific and the most conservative: stop and seek specialist advice when eGFR falls to <20 after a rise; KDIGO/ESC CVD-CKD continuation statements (chronic CKD decline, STOP-ACEi) support continuing in stable slow decline. Engine: continue = caution below 30; flag 'stop/specialist' when an acute fall reaches eGFR <20 or creatinine +100%.

Acceptable creatinine rise / eGFR fall after start or uptitration

“An increase in serum creatinine of <50% above baseline, as long as eGFR remains >15 mL/min/1.73 m2, is considered acceptable.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 66, Section 10.3 Source
“A decrease in eGFR of <30% is acceptable.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 Source
“Practice Point 3.6.4: Continue ACEi or ARB therapy unless serum creatinine rises by more than 30% within 4 weeks following initiation of treatment or an increase in dose.”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 44, Summary of recommendations, Practice Point 3.6.4 (also p. 98) Source
“Therefore, practice guidelines and a previous position paper from this working group propose to tolerate an increase of serum creatinine up to 50% if serum creatinine remains below 3.00 mg/dl and eGFR above >25 ml/min/1.73 m2 when titrating ACE-I/ARB/ARNI.”
Mullens 2022 EJHF: Renal effects of GDMT in HF, HFA/ESC consensus statement (2022)· p. 13 Source
“The current European Society of Cardiology HF guideline recommends continuing renin-angiotensin-aldosterone system agents unless there is a >50% increase in serum creatinine (and serum creatinine is < 3 mg/dl, eGFR is > 25 ml/min per 1.73 m2 , and there is no hyperkalemia).”
Lam CSP, Bozkurt B, Cherney DZI, et al. Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Conclusions From a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. JACC: Heart Failure 2026 (KDIGO Executive Conclusions) (2026)· p. 9

Tool uses esc2026: ESC 2026 main text (<50% creatinine rise with eGFR >15 acceptable) with the Table S4 action ladder (halve if larger rise persists; stop at >100% or eGFR <20). Note internal ESC inconsistency (<30% eGFR fall in Table S4 vs <50% creatinine rise in main text; a 50% creatinine rise is roughly a 33% eGFR fall). KDIGO's 30% trigger is for investigation, not automatic withdrawal.

Potassium thresholds for initiation and withdrawal

“Significant hyperkalaemia (K+ >5.2 mmol/L).”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 10, Table S4 Source
“In patients with eGFR <60 ml/min per 1.73 m2, initiate ACEi, ARB, sMRA, or nsMRA if serum potassium is <5 mEq/l.”
Lam CSP, Bozkurt B, Cherney DZI, et al. Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Conclusions From a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. JACC: Heart Failure 2026 (KDIGO Executive Conclusions) (2026)· p. 11, Figure 4
“If potassium rises to >5.5 mmol/L or creatinine increases by >100% or to eGFR <20 mL/min/1.73 m2, the ACE-I (or ARB) should be stopped and specialist advice sought.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 12, Table S4 Source
“Generally, dose reduction of these agents is advised if potassium is between 5.5 mEq/L and 6 mEq/L and temporarily termination if potassium is above 6 mEq/L, with reinstitution of the drug only when the potassium drops below 5.5 mEq/L.”
Mullens 2022 EJHF: Renal effects of GDMT in HF, HFA/ESC consensus statement (2022)· p. 13 Source
“Severe hyperkalaemia (potassium >5.5 or >6 mmol/L) should lead to temporary down-titration or discontinuation of MRAs and/or ARNIs/ACE-Is/ARBs (see Supplementary data online, Tables S4, S5 and S9).”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 35, Section 6.1.6 Source

Tool uses esc2026-supp: FDA labels give no numeric potassium cutoffs (monitor; dose reduction/discontinuation may be required). Use ESC Table S4: caution to start if K >5.2; acceptable up to 5.5; stop above 5.5 (user-adjustable to 6.0 per Mullens/ESC main text). AHA 2022 also cautions at K >5.0 mEq/L (text not quotable because of two-column extraction).

Dialysis

“There are no data to support the use of these agents in patients with HFrEF with kidney failure (eGFR <15 mL/min/1.73 m2 or dialysis).”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 36, Section 6.2.2.1.1 Source
“In CKD stage 5, the KDIGO guidelines still indicate the use of ACE-I and ARBs with moderate evidence for ACE-I/ARB if CKD stage 5 and dialysis and weak evidence supporting their use in patients with CKD stage 5 not on dialysis.”
Mullens 2022 EJHF: Renal effects of GDMT in HF, HFA/ESC consensus statement (2022)· p. 6 Source
“addition of telmisartan to standard therapies significantly reduces all-cause mortality, cardiovascular death, and heart failure hospital stays in hemodialysis patients with CHF and LVEF ≤ 40%.”
Cice G et al. Telmisartan added to ACE inhibitors in hemodialysis patients with CHF. J Am Coll Cardiol 2010 (PMID 21070920, abstract) (2010)· Abstract (Conclusions) Source
“CONCLUSIONS: BP-lowering treatment with an ARB did not significantly lower the risks of major cardiovascular events or death among patients with hypertension on chronic HD.”
Iseki K, et al. (OCTOPUS) Effects of ARB on mortality and cardiovascular outcomes in patients with long-term haemodialysis: a randomized controlled trial. Nephrol Dial Transplant 2013;28:1579-89 (PubMed abstract, PMID 23355629) (2013)· Abstract (Conclusions) Source

Tool uses esc2026-ckd: Labels do not contraindicate dialysis and the drugs are not dialysed; ESC CVD-CKD finds no supporting data for HFrEF and KDIGO 2026 calls it a knowledge gap; small single-country RCTs are positive but unreplicated (OCTOPUS neutral). Proposed: caution (specialist/individualized) for both initiate and continue rather than 'recommended'.

Starting doses (candesartan, valsartan) and losartan target above the US label maximum

“The recommended starting dose of Diovan is 40 mg twice daily. Uptitrate to 80 mg and 160 mg twice daily or to the highest dose tolerated by the patient.”
DIOVAN (valsartan) PI, Novartis (2026)· Section 2.4 Heart Failure Source
“Valsartan 20–40 mg once daily 160 mg twice daily 254 mg total daily”
2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure (2022)· p. 52, Table 13 Source
“Candesartan 4–8 mg once daily 32 mg once daily 24 mg total daily”
2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure (2022)· p. 52, Table 13 Source
“The dosage can be increased to a maximum dose of 100 mg once daily as needed to control blood pressure [see Clinical Studies (14.1)].”
COZAAR (losartan potassium) tablets, prescribing information, Organon LLC (2026)· Section 2.1 Hypertension Source
“Losartan (12.5) 25–50 mg o.d. 150 mg o.d.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 36, Table 11 Source

Tool uses fda-valsartan: Label > guideline: valsartan start 40 mg b.i.d. (AHA 2022 'once daily' appears to be an error; ACC 2024 and ESC agree with 40 mg b.i.d.); candesartan start 4 mg (FDA, ESC). Losartan has no US HF label: use ESC/ACC/AHA HEAAL target 150 mg o.d. but show an 'off-label in the US (label max 100 mg for hypertension)' note.

ARB added to an ACE inhibitor

“ATACAND also has an added effect on these outcomes when used with an ACE inhibitor [see Drug Interactions (7.4)].”
ATACAND (candesartan) PI, ANI (2025)· Section 1.2 Heart Failure Source
“Thus, there is little evidence of further clinical benefit when valsartan is added to an adequate dose of ACE inhibitor.”
DIOVAN (valsartan) PI, Novartis (2026)· Section 14.2 Heart Failure Source
“Combined use of an ARB with an ACEI is not recommended in patients with CKD as the risk of AKI and severe hyperkalaemia outweighs any added cardiorenal benefits.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 31, Recommendation Table 12 (Class III) Source

Tool uses esc2026-ckd: ESC 2026 positions the ARB only as an alternative when ACE-I/ARNI are not tolerated; combination is Class III in CKD. Engine should treat ARB as mutually exclusive with ACE-I and ARNI.

Open questions

CKD G5 (not on dialysis) initiation: set to 'not-recommended' (conservative; ESC CVD-CKD no data, ESC HF Table S4 stop rule at eGFR <20, ESC HF temporary discontinuation at eGFR <15). KDIGO 2024/Mullens would allow cautious use; owner to confirm.
Dialysis: proposed 'caution' for both initiate and continue based on labels (no contraindication, not dialysed) and small HD RCTs; ESC CVD-CKD says no supporting data. Owner may prefer 'no-data'.
KDIGO 2026 HF Figure 4 lists no ACEi/ARB/ARNI for HFrEF with eGFR 15-29 and Table 2 (HF guidance) uses creatinine <2.5 mg/dL or eGFR >30, unlike ESC CVD-CKD IIb for 15-29. Decide whether the engine shows G4 initiation as caution (proposed) or not-recommended.
Losartan: no FDA HF indication; HEAAL target 150 mg exceeds the US label maximum (100 mg). Show an off-label badge?
Trial renal exclusions: CHARM serum creatinine >3 mg/dL is quoted from the FDA label. Val-HeFT and HEAAL creatinine cutoffs come only from review tables that the PDF extraction scrambled (Mullens 2022 Table 1 suggests Cr >2.5 mg/dL for both; Beldhuis 2022 Fig 2B pairs Val-HeFT with >3.4), so they are not quoted. Primary papers (NEJM 2001, Lancet 2009) are paywalled.
ESC CVD-CKD Figure 12 footnote equates 300 umol/L with 'around 2.5 mg/dL' (300 umol/L is about 3.4 mg/dL); use with care if adopted as a threshold.
Transplant: only a KDIGO hypertension recommendation (ARB or CCB first-line); no HF-specific data. Proposed 'allowed' and apply graft-eGFR rules.

Angiotensin II receptor blockers (ARBs)

FMT in HFrEF · Class IAMT in HFpEF · Class IIb

Open in the matrix

Removal by dialysis

What each drug's prescribing information says about removal by (haemo)dialysis. Where the label is silent, this page says so rather than inferring from protein binding.

CandesartanNot removed (or not meaningfully removed)
- “Candesartan cannot be removed by hemodialysis.”
  ATACAND (candesartan) PI, ANI (2025)· 10 OVERDOSAGE Source
LosartanNot removed (or not meaningfully removed)
- “Neither losartan nor its active metabolite can be removed by hemodialysis.”
  COZAAR (losartan potassium) tablets, prescribing information, Organon LLC (2026)· 10 OVERDOSAGE Source
ValsartanNot removed (or not meaningfully removed)
- “Diovan (valsartan) is not removed from the plasma by hemodialysis.”
  DIOVAN (valsartan) PI, Novartis (2026)· 10 OVERDOSAGE Source

After starting: what a change in creatinine, eGFR or potassium means

“Some rise in urea (BUN), creatinine, and potassium is to be expected after an ACE-I; if an increase is small, no action is necessary.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 Source
“A decrease in eGFR of <30% is acceptable.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 Source
“An increase in potassium to ≤5.5 mmol/L is acceptable.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 Source
“If greater rises in creatinine or potassium than those outlined above persist despite adjustment of concomitant medications, the dose of the ACE-I (or ARB) should be halved and blood chemistry rechecked within 1–2 weeks; if there is still an unsatisfactory response, specialist advice should be sought.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 12, Table S4 Source
“If potassium rises to >5.5 mmol/L or creatinine increases by >100% or to eGFR <20 mL/min/1.73 m2, the ACE-I (or ARB) should be stopped and specialist advice sought.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 12, Table S4 Source

“Hemodynamic fluctuations in eGFR up to 30% can be seen and should not lead to discontinuation”
Lam CSP, Bozkurt B, Cherney DZI, et al. Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Conclusions From a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. JACC: Heart Failure 2026 (KDIGO Executive Conclusions) (2026)· p. 10
“If >30%, other causes of AKI should be evaluated”
Lam CSP, Bozkurt B, Cherney DZI, et al. Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Conclusions From a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. JACC: Heart Failure 2026 (KDIGO Executive Conclusions) (2026)· p. 10
“An increase in serum creatinine of <50% above baseline, as long as eGFR remains >15 mL/min/1.73 m2, is considered acceptable.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 66, Section 10.3 Source
“Worsening kidney function alone is not an independent determinant of outcomes in patients with acute HF.”
Lam CSP, Bozkurt B, Cherney DZI, et al. Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Conclusions From a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. JACC: Heart Failure 2026 (KDIGO Executive Conclusions) (2026)· p. 11

Drugs and doses

Drug	Brands	Start	Target	Kidney dosing
Candesartan	Atacand	4 mg o.d. (AHA 2022 / ACC 2024: 4-8 mg o.d.)	32 mg o.d.	FDA: no initial dose adjustment for renal insufficiency; exposure ~doubled when CrCl <30 and similar on haemodialysis; not removed by haemodialysis. US HF indication: NYHA II-IV, LVEF <=40% (CHARM excluded serum creatinine >3 mg/dL and K >5.5 mEq/L).
Losartan	Cozaar	(12.5) 25-50 mg o.d.	150 mg o.d. (HEAAL; above the US label maximum of 100 mg/day)	FDA: no dose adjustment in renal impairment unless also volume depleted (then start 25 mg); exposure up 50-90% in mild-moderate renal insufficiency; neither losartan nor its active metabolite is removed by haemodialysis. NO US heart-failure indication (HF use is off-label; ESC/ACC/AHA list it).
Valsartan	Diovan	40 mg b.i.d.	160 mg b.i.d.	FDA: no dose adjustment for GFR 30-90; safety and effectiveness not established for GFR <30; no correlation between CrCl and exposure down to CrCl 10 mL/min; not removed by haemodialysis. US HF indication is to reduce HF hospitalization only (no added benefit on top of an adequate ACE-I dose).

Status by kidney stage

Stage	Initiate	Continue
G1	Recommended Class I FMT alternative in HFrEF when ACE-I and ARNI are not tolerated; candesartan and valsartan carry US HF indications; no renal restriction.	Recommended Continue at highest tolerated dose; routine K+/creatinine monitoring.
G2	Recommended As G1; FDA valsartan label: no dose adjustment for GFR 60-90.	Recommended Continue; monitor renal function and potassium periodically.
G3a	Recommended ESC CVD-CKD Class I for eGFR >=30; no label dose adjustment for moderate renal impairment (losartan exposure 50-90% higher, no adjustment).	Recommended Continue; an initial creatinine rise is expected and is not a reason to stop.
G3b	Recommended Still covered by the ESC CVD-CKD Class I recommendation (eGFR >=30); ESC CVD-CKD suggests a more cautious titration below eGFR ~40.	Recommended Continue despite an eGFR dip; titrate cautiously given limited kidney reserve.
G4	Use with caution May be considered (ESC CVD-CKD Class IIb, C) at low dose with slow titration and close K+/eGFR monitoring; ESC HF Table S4 lists eGFR <30 as 'caution/seek specialist advice'; valsartan label: safety not established below GFR 30.	Use with caution Continue under close monitoring (KDIGO: continue even when eGFR falls below 30); stop if eGFR falls to <20 or creatinine rises >100% (ESC Table S4).
G5	Not recommended No HF data below eGFR 15 (ESC CVD-CKD); ESC HF advises temporary discontinuation may be needed at eGFR <15 and Table S4 stops ACE-I/ARB if eGFR falls <20; do not start outside specialist care (conservative choice).	Use with caution Individualize: KDIGO supports continuing (STOP-ACEi showed no benefit of stopping at mean eGFR 13) but allows dose reduction/withdrawal for uraemic symptoms, hyperkalaemia or hypotension; ESC HF: temporary discontinuation may be needed.
dialysis	Use with caution Not contraindicated by any label; candesartan/losartan/valsartan are not removed by haemodialysis and need no label dose change, but ESC CVD-CKD states there are no data supporting HFrEF use on dialysis and KDIGO 2026 calls G5D a knowledge gap; small dialysis RCTs (telmisartan in HFrEF on HD; candesartan; mixed ARBs) were positive, OCTOPUS (olmesartan) neutral. Nephrology/HF specialist decision; watch intradialytic hypotension and hyperkalaemia.	Use with caution Continuation reasonable if BP and potassium allow; individualize with nephrology.
aki	Not recommended Do not start during AKI; initiate only in stable patients after recovery (ESC Table S4: in hospital after stabilizing).	Use with caution Consider withholding (labels; ESC HF) when AKI is clinically significant: stop if creatinine rises >100%, eGFR falls <20 or K >5.5 (ESC Table S4); halve dose for smaller excess rises; a rise <50% with eGFR >15 is acceptable (ESC HF). Restart when renal function recovers (2-4 weeks; within 14 days restart at prior dose).
transplant	Allowed No HF-specific transplant data; KDIGO 2021 BP recommends an ARB (or dihydropyridine CCB) as first-line antihypertensive in kidney transplant recipients; apply the eGFR rules of the graft and involve the transplant team.	Allowed Continue per graft eGFR and potassium; coordinate with transplant team (drug interactions, hyperkalaemia with calcineurin inhibitors).

Cutoffs recorded from the sources

potassium > 5.2 mmol/L → caution (initiate; candesartan, losartan, valsartan)
“Significant hyperkalaemia (K+ >5.2 mmol/L).” — esc2026-supp, p. 10, Table S4 (Cautions/seek specialist advice)
potassium >= 5 mmol/L → not-recommended (initiate; candesartan, losartan, valsartan)
“In patients with eGFR <60 ml/min per 1.73 m2, initiate ACEi, ARB, sMRA, or nsMRA if serum potassium is <5 mEq/l.” — kdigo2026-hf, p. 11, Figure 4
egfr < 30 mL/min/1.73m2 → caution (initiate; candesartan, losartan, valsartan)
“Significant renal dysfunction (eGFR <30 mL/min/1.73 m2). May be considered in lower eGFR under close monitoring of eGFR after initiation.” — esc2026-supp, p. 10, Table S4 (Cautions/seek specialist advice)
egfr < 30 mL/min/1.73m2 → caution (initiate; valsartan)
“Safety and effectiveness of Diovan in patients with severe renal impairment (glomerular filtration rate less than 30 mL/min/1.73 m2) have not been established.” — fda-valsartan, Section 8.6 Renal Impairment
egfr < 15 mL/min/1.73m2 → not-recommended (initiate; candesartan, losartan, valsartan)
“There are no data to support the use of these agents in patients with HFrEF with kidney failure (eGFR <15 mL/min/1.73 m2 or dialysis).” — esc2026-ckd, p. 36, Section 6.2.2.1.1
egfr < 40 mL/min/1.73m2 → caution (uptitrate; candesartan, losartan, valsartan)
“A more cautious approach could be applied in patients with moderate or severe CKD (e.g. eGFR <40 mL/min/1.73 m2) given limited kidney reserve.” — esc2026-ckd, p. 44, Section 6.4
sbp < 90 mmHg → caution (initiate; candesartan, losartan, valsartan)
“Symptomatic or severe asymptomatic hypotension (systolic blood pressure <90 mmHg).” — esc2026-supp, p. 10, Table S4 (Cautions/seek specialist advice)
creatinine_abs >= 2.5 mg/dL → caution (initiate; candesartan, losartan, valsartan)
“ACEi or ARB All persons with CKD, and moderate or severe albuminuria in persons with and without diabetes Should be continued in CKD even when eGFR declines to <30 ml/min per 1.73 m2 Serum creatinine <221 mmol/l (<2.5 mg/dl) or eGFR > 30 ml/min per 1.73 m2” — kdigo2026-hf, p. 10, Table 2
creatinine_abs > 3 mg/dL → caution (initiate; candesartan)
“Patients with serum creatinine > 3 mg/dL, serum potassium > 5.5 mEq/L, symptomatic hypotension or known bilateral renal artery stenosis were excluded.” — fda-candesartan, Section 14.2 Heart Failure
other < 30 % decrease in eGFR → allowed (continue; candesartan, losartan, valsartan)
“A decrease in eGFR of <30% is acceptable.” — esc2026-supp, p. 11, Table S4 (Problem solving)
creatinine_rise_pct < 50 % above baseline → allowed (continue; candesartan, losartan, valsartan)
“An increase in serum creatinine of <50% above baseline, as long as eGFR remains >15 mL/min/1.73 m2, is considered acceptable.” — esc2026, p. 66, Section 10.3
creatinine_rise_pct > 100 % above baseline → not-recommended (hold; candesartan, losartan, valsartan)
“If potassium rises to >5.5 mmol/L or creatinine increases by >100% or to eGFR <20 mL/min/1.73 m2, the ACE-I (or ARB) should be stopped and specialist advice sought.” — esc2026-supp, p. 12, Table S4 (Problem solving)
egfr < 20 mL/min/1.73m2 → not-recommended (hold; candesartan, losartan, valsartan)
“If potassium rises to >5.5 mmol/L or creatinine increases by >100% or to eGFR <20 mL/min/1.73 m2, the ACE-I (or ARB) should be stopped and specialist advice sought.” — esc2026-supp, p. 12, Table S4 (Problem solving)
potassium > 5.5 mmol/L → not-recommended (hold; candesartan, losartan, valsartan)
“If potassium rises to >5.5 mmol/L or creatinine increases by >100% or to eGFR <20 mL/min/1.73 m2, the ACE-I (or ARB) should be stopped and specialist advice sought.” — esc2026-supp, p. 12, Table S4 (Problem solving)
potassium <= 5.5 mmol/L → allowed (continue; candesartan, losartan, valsartan)
“An increase in potassium to ≤5.5 mmol/L is acceptable.” — esc2026-supp, p. 11, Table S4 (Problem solving)
potassium > 5.5 mmol/L → caution (dose_reduce; candesartan, losartan, valsartan)
“Severe hyperkalaemia (potassium >5.5 or >6 mmol/L) should lead to temporary down-titration or discontinuation of MRAs and/or ARNIs/ACE-Is/ARBs (see Supplementary data online, Tables S4, S5 and S9).” — esc2026, p. 35, Section 6.1.6
potassium > 6 mEq/L → not-recommended (hold; candesartan, losartan, valsartan)
“Generally, dose reduction of these agents is advised if potassium is between 5.5 mEq/L and 6 mEq/L and temporarily termination if potassium is above 6 mEq/L, with reinstitution of the drug only when the potassium drops below 5.5 mEq/L.” — mullens2022, p. 13
creatinine_rise_pct > 50 % above baseline → not-recommended (hold; candesartan, losartan, valsartan)
“In contrast, only if serum creatinine rises by >50% or above 3.5 mg/dl treatment should be discontinued with re-challenge when possible” — mullens2022, p. 13
creatinine_abs > 3.5 mg/dL → not-recommended (hold; candesartan, losartan, valsartan)
“In contrast, only if serum creatinine rises by >50% or above 3.5 mg/dl treatment should be discontinued with re-challenge when possible” — mullens2022, p. 13
creatinine_rise_pct > 30 % within 4 weeks of start/dose increase → caution (continue; candesartan, losartan, valsartan)
“Practice Point 3.6.4: Continue ACEi or ARB therapy unless serum creatinine rises by more than 30% within 4 weeks following initiation of treatment or an increase in dose.” — kdigo2024-ckd, p. 44, Summary of recommendations, Practice Point 3.6.4 (also p. 98)
egfr < 15 mL/min/1.73m2 → caution (continue; candesartan, losartan, valsartan)
“However, temporary discontinuation of MRAs/ARNIs/ACE-Is/ARBs and SGLT2-Is may be needed in cases with acute kidney injury and eGFR <15 mL/min/1.73 m2.” — esc2026, p. 35, Section 6.1.6
creatinine_rise_pct > 50 % above baseline (decompensated HF) → caution (hold; candesartan, losartan, valsartan)
“CAUTION IN CASE OF >50% increase in serum creatinine or absolute serum creatinine increases above >300 μmol/L” — esc2026-ckd, p. 45, Figure 12

Trial evidence (informational)

CHARM-Alternative · HFrEF (LVEF <=40%), ACE-I intolerant; serum creatinine >3 mg/dL excluded
CV death or HF hospitalization: HR 0.77 (95% CI 0.67-0.89); covariate adjusted 0.70 (0.60-0.81)
“During a median follow-up of 33.7 months, 334 (33%) of 1013 patients in the candesartan group and 406 (40%) of 1015 in the placebo group had cardiovascular death or hospital admission for CHF (unadjusted hazard ratio 0.77 [95% CI 0.67-0.89], p=0.0004; covariate adjusted 0.70 [0.60-0.81], p<0.0001).” — granger2003, Abstract (Findings)
CHARM-Added · HFrEF (LVEF <=40%) on an ACE inhibitor
CV death or HF hospitalization: 15% relative risk reduction (HR 0.85, 95% CI 0.75-0.96)
“After a median follow-up of 41 months, there was a 15% reduction in the risk of cardiovascular death or heart failure hospitalization on ATACAND (p=0.011), with both components contributing to the overall effect (Table 2).” — fda-candesartan, Section 14.2 Heart Failure
HEAAL · HFrEF (LVEF <=40%), ACE-I intolerant; losartan 150 vs 50 mg
Death or HF admission: HR 0.90 (95% CI 0.82-0.99)
“With 4.7-year median follow-up in each group (IQR 3.7-5.5 for losartan 150 mg; 3.4-5.5 for losartan 50 mg), 828 (43%) patients in the 150 mg group versus 889 (46%) in the 50 mg group died or were admitted for heart failure (hazard ratio [HR] 0.90, 95% CI 0.82-0.99; p=0.027).” — konstam2009, Abstract (Findings)
HEAAL (safety) · as above
Renal impairment, hypotension, hyperkalaemia: More frequent with 150 mg than 50 mg, without more discontinuations
“Renal impairment (n=454 vs 317), hypotension (203 vs 145), and hyperkalaemia (195 vs 131) were more common in the 150 mg group than in the 50 mg group, but these adverse events did not lead to significantly more treatment discontinuations in the 150 mg group.” — konstam2009, Abstract (Findings)
Val-HeFT · HF NYHA II-IV, LVEF <40%, ~93% on ACE-I
Combined mortality and morbidity: RR 0.87 (97.5% CI 0.77-0.97); no mortality effect
“The incidence of the combined end point, however, was 13.2 percent lower with valsartan than with placebo (relative risk, 0.87; 97.5 percent confidence interval, 0.77 to 0.97; P=0.009), predominantly because of a lower number of patients hospitalized for heart failure; 455 (18.2 percent) in the placebo group and 346 (13.8 percent) in the valsartan group (P<0.001).” — cohn2001, Abstract (Results)
Val-HeFT (no ACE-I subgroup) · Val-HeFT patients not on an ACE inhibitor (n=366)
HF morbidity: HR 0.51 (95% CI 0.35-0.73); little benefit when added to adequate ACE-I
“Thus, there is little evidence of further clinical benefit when valsartan is added to an adequate dose of ACE inhibitor.” — fda-valsartan, Section 14.2 Heart Failure
CHARM-Preserved · HF with LVEF >40%
CV death or HF admission: HR 0.89 (95% CI 0.77-1.03), not significant; fewer HF admissions
“333 (22%) patients in the candesartan and 366 (24%) in the placebo group experienced the primary outcome (unadjusted hazard ratio 0.89 [95% CI 0.77-1.03], p=0.118; covariate adjusted 0.86 [0.74-1.0], p=0.051).” — yusuf2003, Abstract (Findings)
ARB meta-analysis in HFpEF (4 trials) · HFpEF
CV death, all-cause death, HFH: No signal for benefit (HFH HR 0.92, 95% CI 0.83-1.02)
“In a meta-analysis of four trials evaluating ARBs in patients with HFpEF, there was no signal for benefit on CV death (HR 1.02), all-cause death (HR 1.01; 95% CI 0.92–1.11), or HFH (HR 0.92; 95% CI 0.83–1.02).” — esc2026, p. 36, Section 6.1.7.1
ESC 2026 overall assessment · HFrEF
All-cause mortality: No ARB has reduced all-cause mortality
“However, no ARB has reduced all-cause mortality in any trial, and combination with an ACE-I increases adverse effects.” — esc2026, p. 33, Section 6.1.4.2
Cice 2010 (telmisartan, not an ESC-listed ARB) · Haemodialysis patients with HFrEF (LVEF <=40%) on ACE-I
All-cause mortality: HR 0.51 (95% CI 0.32-0.82)
“With Cox proportional hazards analysis, telmisartan was an independent determinant of all-cause mortality (hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.32 to 0.82; p < 0.01), cardiovascular mortality (HR: 0.42; 95% CI: 0.38 to 0.61; p < 0.0001), and hospital stay for deterioration of heart failure (HR: 0.38; 95% CI: 0.19 to 0.51; p < 0.0001).” — cice2010, Abstract (Results)

Acute kidney injury

“Thus, a transient decrease in kidney function after the initiation of ACE-Is/ARNIs/ARBs and MRAs or SGLT2-Is should not prompt their interruption.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 66, Section 10.3 Source
“If urea, creatinine, or potassium does rise excessively, consider stopping concomitant nephrotoxic drugs (e.g. NSAIDsc) and other potassium supplements or retaining agents (triamterene, amiloride) and, if no signs of congestion, reducing the dose of diuretic.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 (Problem solving) Source
“If greater rises in creatinine or potassium than those outlined above persist despite adjustment of concomitant medications, the dose of the ACE-I (or ARB) should be halved and blood chemistry rechecked within 1–2 weeks; if there is still an unsatisfactory response, specialist advice should be sought.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 12, Table S4 (Problem solving) Source
“Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on COZAAR [see Drug Interactions (7.3) and Use in Specific Populations (8.7)].”
COZAAR (losartan potassium) tablets, prescribing information, Organon LLC (2026)· Warnings and Precautions 5.3 Source
“Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Diovan [see Drug Interactions (7)].”
DIOVAN (valsartan) PI, Novartis (2026)· Warnings and Precautions 5.3 Source
“After possible (temporary) downtitration or even discontinuation, a rechallenge should be considered when renal function (and potassium) has recovered after 2 to 4 weeks.”
Beldhuis 2022 Circulation: Evidence-based medical therapy in HFrEF patients with CKD (2022)· p. 4 Source
“In the context of uptitration of ARBs some increase in serum creatinine / drop in eGFR is expected and acceptable.”
Beldhuis 2022 Circulation: Evidence-based medical therapy in HFrEF patients with CKD (2022)· p. 6, Figure 2B (ARB panel) Source
“Although not supported by any strong evidence, patients may be counselled to withhold ACEI/ARBs, SGLT2 inhibitors, non-steroidal MRAs, and GLP-1RAs temporarily if not able to maintain oral intake (‘sick day rules’).”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 31, Section 5.5 Source
“However, there is a paucity of evidence to support sick day rules to prevent AKI or other clinically relevant outcomes.”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 136, Section 4.3 Source
“If FMT has been temporarily discontinued for less than 14 days, it should, in most cases, be safe to initiate FMT directly at the previously tolerated doses in stable patients.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 35, Section 6.1.6 Source
“Patients whose renal function may depend, in part, on the activity of the renin-angiotensin system (e.g., patient with renal artery stenosis, chronic kidney disease, severe heart failure, or volume depletion) may be at particular risk of developing oliguria, progressive azotemia or acute renal failure when treated with ATACAND.”
ATACAND (candesartan) PI, ANI (2025)· Warnings and Precautions 5.4 Source

Dialysis

Trials: Cice 2010 (telmisartan in HD with HFrEF), Takahashi 2006 (candesartan in HD)

“Neither losartan nor its active metabolite can be removed by hemodialysis.”
COZAAR (losartan potassium) tablets, prescribing information, Organon LLC (2026)· Section 10 Overdosage Source
“There is no apparent correlation between renal function (measured by creatinine clearance) and exposure (measured by AUC) to valsartan in patients with different degrees of renal impairment (down to creatinine clearance of 10 mL/min).”
DIOVAN (valsartan) PI, Novartis (2026)· Section 12.3 Pharmacokinetics (Renal Insufficiency) Source
“Diovan (valsartan) is not removed from the plasma by hemodialysis.”
DIOVAN (valsartan) PI, Novartis (2026)· Section 10 Overdosage Source
“Symptomatic hypotension is most likely to occur in patients who have been volume and/or salt depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting.”
ATACAND (candesartan) PI, ANI (2025)· Warnings and Precautions 5.3 Source
“There are no data to support the use of these agents in patients with HFrEF with kidney failure (eGFR <15 mL/min/1.73 m2 or dialysis).”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 36, Section 6.2.2.1.1 Source
“However, in CKD G5D, the efﬁcacy and safety of GDMT remain knowledge gaps.”
Lam CSP, Bozkurt B, Cherney DZI, et al. Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Conclusions From a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. JACC: Heart Failure 2026 (KDIGO Executive Conclusions) (2026)· p. 9
“In CKD stage 5, the KDIGO guidelines still indicate the use of ACE-I and ARBs with moderate evidence for ACE-I/ARB if CKD stage 5 and dialysis and weak evidence supporting their use in patients with CKD stage 5 not on dialysis.”
Mullens 2022 EJHF: Renal effects of GDMT in HF, HFA/ESC consensus statement (2022)· p. 6 Source
“RESULTS: at 3 years, telmisartan significantly reduced all-cause mortality (35.1% vs. 54.4%; p < 0.001), cardiovascular death (30.3% vs. 43.7%; p < 0.001), and hospital admission for CHF (33.9% vs. 55.1%; p < 0.0001).”
Cice G et al. Telmisartan added to ACE inhibitors in hemodialysis patients with CHF. J Am Coll Cardiol 2010 (PMID 21070920, abstract) (2010)· Abstract (Results) Source
“CONCLUSIONS: Candesartan therapy significantly reduces cardiovascular events and mortality in patients on chronic maintenance haemodialysis and therefore improves the prognosis of these patients.”
Takahashi A et al. Candesartan reduces cardiovascular events in chronic haemodialysis. Nephrol Dial Transplant 2006 (PMID 16766543, abstract) (2006)· Abstract (Conclusions) Source
“After adjustment for age, sex, diabetes, systolic blood pressure, and center, treatment with an ARB was independently associated with reduced fatal and nonfatal CVD events (hazard ratio, 0.51; 95% confidence interval, 0.33 to 0.79; P = 0.002).”
Suzuki H, et al. Effect of angiotensin receptor blockers on cardiovascular events in patients undergoing hemodialysis: an open-label randomized controlled trial. Am J Kidney Dis 2008;52:501-6 (PubMed abstract, PMID 18653268) (2008)· Abstract (Results) Source
“CONCLUSIONS: BP-lowering treatment with an ARB did not significantly lower the risks of major cardiovascular events or death among patients with hypertension on chronic HD.”
Iseki K, et al. (OCTOPUS) Effects of ARB on mortality and cardiovascular outcomes in patients with long-term haemodialysis: a randomized controlled trial. Nephrol Dial Transplant 2013;28:1579-89 (PubMed abstract, PMID 23355629) (2013)· Abstract (Conclusions) Source
“Safety and effectiveness of Diovan in patients with severe renal impairment (glomerular filtration rate less than 30 mL/min/1.73 m2) have not been established.”
DIOVAN (valsartan) PI, Novartis (2026)· Section 8.6 Source
“The pharmacokinetics of candesartan in hypertensive patients undergoing hemodialysis are similar to those in hypertensive patients with severe renal impairment. Candesartan cannot be removed by hemodialysis.”
ATACAND (candesartan) PI, ANI (2025)· Section 12.3 Source

Kidney transplant

“Recommendation 4.1: We recommend that a dihydropyridine calcium channel blocker (CCB) or an ARB be used as the ﬁrst-line antihypertensive agent in adult kidney transplant recipients (1C).”
KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in CKD (2021)· p. 30, Recommendation 4.1 Source
“When initiating new treatment, consultation with the patient’s transplant team is advisable to ensure that there are no important considerations for the graft, and particularly relevant drug interactions.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 72, Section 13.2.2 Source
“In the early posttransplant period, ARBs should be avoided until kidney transplant function stabilizes, as the acute negative effect of an ARB on GFR can be confused with other causes of graft dysfunction (e.g., rejection).”
KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in CKD (2021)· p. 62, Recommendation 4.1 rationale Source

Albuminuria

“Recommendation 3.6.3: We recommend starting RASi (ACEi or ARB) for people with CKD and moderately-to-severely increased albuminuria (G1–G4, A2 and A3) with diabetes (1B).”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 43, Summary of recommendations, Recommendation 3.6.3 (also p. 98) Source
“Practice Point 3.6.6: Consider starting people with CKD with normal to mildly increased albuminuria (A1) on RASi (ACEi or ARB) for speciﬁc indications (e.g., to treat hypertension or heart failure with low ejection fraction).”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 44, Summary of recommendations, Practice Point 3.6.6 (also p. 98) Source
“Angiotensin-converting enzyme inhibitors or ARBs are recommended for most patients with CKD. One might consider not prescribing an ACEI/ARB in patients with normal/low blood pressure without albuminuria (unless there is another indication for use).”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 28, Section 5.5 Source
“COZAAR is indicated for the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (urinary albumin to creatinine ratio ≥300 mg/g) in patients with type 2 diabetes and a history of hypertension.”
COZAAR (losartan potassium) tablets, prescribing information, Organon LLC (2026)· Section 1.3 Nephropathy in Type 2 Diabetic Patients Source

Monitoring

“Recheck blood chemistry (urea/BUN, creatinine, K+) 1–2 weeks after initiation and 1–2 weeks after final dose titration.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 (How to use?) Source
“Monitor blood chemistry 4–6 monthly thereafter.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 (How to use?) Source
“Practice Point 3.6.2: Changes in BP, serum creatinine, and serum potassium should be checked within 2–4 weeks of initiation or increase in the dose of a RASi, depending on the current GFR and serum potassium.”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 44, Summary of recommendations, Practice Point 3.6.2 (also p. 98) Source
“Extra biochemical monitoring after initiation of SGLT2 inhibitors or GLP-1RAs is not routinely required, but 1–4 weeks after initiation of RAAS blockade serum potassium and eGFR should be re-checked”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 75, Section 15/16 key messages Source
“In the ACE-I/ARB/ARNI and SGLT2 inhibitor trials, laboratory assessment of creatinine, urea, eGFR and electrolytes was typically done after 14 days during drug titration and every 4 months thereafter.”
Mullens 2022 EJHF: Renal effects of GDMT in HF, HFA/ESC consensus statement (2022)· p. 14 Source
“Monitor serum potassium periodically.”
ATACAND (candesartan) PI, ANI (2025)· Warnings and Precautions 5.5 Source
“Triple combination of ATACAND with an ACE-inhibitor and a mineralocorticoid receptor antagonist is generally not recommended.”
ATACAND (candesartan) PI, ANI (2025)· Drug Interactions 7.4 Source
“Combined use of an ARB with an ACEI is not recommended in patients with CKD as the risk of AKI and severe hyperkalaemia outweighs any added cardiorenal benefits.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 31, Recommendation Table 12 (Class III) Source
“Some patients with heart failure have developed increases in potassium. These effects are usually minor and transient, and they are more likely to occur in patients with pre-existing renal impairment.”
DIOVAN (valsartan) PI, Novartis (2026)· Warnings and Precautions 5.4 Source

In-hospital initiation

“In patients already receiving FMT, continuation and/or rapid reintroduction as soon as possible is recommended. Discontinuation of FMT is not recommended unless there are clear signs of hypoperfusion or specific clinical indications.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 45, Section 7.4.1 Source
“In patients hospitalized with DHF—after stabilizing (but ideally before discharge).”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 (Where?) Source
“In patients experiencing mild decrease of renal function or asymptomatic reduction of blood pressure during HF hospitalization, diuresis and other GDMT should not routinely be discontinued (6-11).”
2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure (2022)· p. 80, Section 8 recommendation 2 Source
“Temporary discontinuation of beta-blockers and ARNIs/ACE-Is/ARBs is advised in patients with severe haemodynamic instability.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 35, Section 6.1.6 Source

Outpatient

“In the community in stable patients (NYHA class IV/patients with advanced HF and those with a current/recent exacerbation should be referred for specialist advice).”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 (Where?) Source
“In those patients where close monitoring is not possible, dose should be doubled at not less than 2-week intervals.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 (How to use?) Source
“It is very rarely necessary to stop an ACE-I (or ARB), and clinical deterioration is likely if treatment is withdrawn.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 (How to use?) Source

Where sources disagree

Initiation at eGFR 15-29 (CKD G4)

“Treatment with an ACEI or ARB may be considered in patients with HFrEF and CKD with an eGFR 15–29 mL/min/1.73 m2 to reduce the risk of HF hospitalization and cardiovascular death.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 39, Recommendation Table 15 (Class IIb, C) Source
“Significant renal dysfunction (eGFR <30 mL/min/1.73 m2). May be considered in lower eGFR under close monitoring of eGFR after initiation.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 10, Table S4 Source
“Safety and effectiveness of Diovan in patients with severe renal impairment (glomerular filtration rate less than 30 mL/min/1.73 m2) have not been established.”
DIOVAN (valsartan) PI, Novartis (2026)· Section 8.6 Renal Impairment Source
“<15 15–29 30–59 ≥60 • ß-blocker • Hydralazine/ nitrates • ß-blocker • SGLT2i if eGFR >20 • Vericiguat • ß-blocker • ARNI, ACEi, or ARB”
Lam CSP, Bozkurt B, Cherney DZI, et al. Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Conclusions From a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. JACC: Heart Failure 2026 (KDIGO Executive Conclusions) (2026)· p. 11, Figure 4 (HFrEF columns <15, 15–29, 30–59, ≥60)
“We are aligned with KDIGO guideline recommendation to use ACE-I/ARB also in more advanced CKD stages (stage 4–5).”
Mullens 2022 EJHF: Renal effects of GDMT in HF, HFA/ESC consensus statement (2022)· p. 6 Source

Continuation as eGFR falls below 30 / below 20 / below 15

“Practice Point 3.6.7: Continue ACEi or ARB in people with CKD even when the eGFR falls below 30 ml/min per 1.73 m2.”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 44, Summary of recommendations, Practice Point 3.6.7 (also p. 98) Source
“If potassium rises to >5.5 mmol/L or creatinine increases by >100% or to eGFR <20 mL/min/1.73 m2, the ACE-I (or ARB) should be stopped and specialist advice sought.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 12, Table S4 Source
“An increase in serum creatinine of <50% above baseline, as long as eGFR remains >15 mL/min/1.73 m2, is considered acceptable.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 66, Section 10.3 Source
“With potassium monitoring, ACEI/ARBs can safely be continued as kidney function declines to severe CKD and kidney failure to manage blood pressure and cardiovascular risk.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 28, Section 5.5 Source

Acceptable creatinine rise / eGFR fall after start or uptitration

“An increase in serum creatinine of <50% above baseline, as long as eGFR remains >15 mL/min/1.73 m2, is considered acceptable.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 66, Section 10.3 Source
“A decrease in eGFR of <30% is acceptable.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 Source
“Practice Point 3.6.4: Continue ACEi or ARB therapy unless serum creatinine rises by more than 30% within 4 weeks following initiation of treatment or an increase in dose.”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 44, Summary of recommendations, Practice Point 3.6.4 (also p. 98) Source
“Therefore, practice guidelines and a previous position paper from this working group propose to tolerate an increase of serum creatinine up to 50% if serum creatinine remains below 3.00 mg/dl and eGFR above >25 ml/min/1.73 m2 when titrating ACE-I/ARB/ARNI.”
Mullens 2022 EJHF: Renal effects of GDMT in HF, HFA/ESC consensus statement (2022)· p. 13 Source
“The current European Society of Cardiology HF guideline recommends continuing renin-angiotensin-aldosterone system agents unless there is a >50% increase in serum creatinine (and serum creatinine is < 3 mg/dl, eGFR is > 25 ml/min per 1.73 m2 , and there is no hyperkalemia).”
Lam CSP, Bozkurt B, Cherney DZI, et al. Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Conclusions From a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. JACC: Heart Failure 2026 (KDIGO Executive Conclusions) (2026)· p. 9

Potassium thresholds for initiation and withdrawal

“Significant hyperkalaemia (K+ >5.2 mmol/L).”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 10, Table S4 Source
“In patients with eGFR <60 ml/min per 1.73 m2, initiate ACEi, ARB, sMRA, or nsMRA if serum potassium is <5 mEq/l.”
Lam CSP, Bozkurt B, Cherney DZI, et al. Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Conclusions From a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. JACC: Heart Failure 2026 (KDIGO Executive Conclusions) (2026)· p. 11, Figure 4
“If potassium rises to >5.5 mmol/L or creatinine increases by >100% or to eGFR <20 mL/min/1.73 m2, the ACE-I (or ARB) should be stopped and specialist advice sought.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 12, Table S4 Source
“Generally, dose reduction of these agents is advised if potassium is between 5.5 mEq/L and 6 mEq/L and temporarily termination if potassium is above 6 mEq/L, with reinstitution of the drug only when the potassium drops below 5.5 mEq/L.”
Mullens 2022 EJHF: Renal effects of GDMT in HF, HFA/ESC consensus statement (2022)· p. 13 Source
“Severe hyperkalaemia (potassium >5.5 or >6 mmol/L) should lead to temporary down-titration or discontinuation of MRAs and/or ARNIs/ACE-Is/ARBs (see Supplementary data online, Tables S4, S5 and S9).”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 35, Section 6.1.6 Source

Dialysis

“There are no data to support the use of these agents in patients with HFrEF with kidney failure (eGFR <15 mL/min/1.73 m2 or dialysis).”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 36, Section 6.2.2.1.1 Source
“In CKD stage 5, the KDIGO guidelines still indicate the use of ACE-I and ARBs with moderate evidence for ACE-I/ARB if CKD stage 5 and dialysis and weak evidence supporting their use in patients with CKD stage 5 not on dialysis.”
Mullens 2022 EJHF: Renal effects of GDMT in HF, HFA/ESC consensus statement (2022)· p. 6 Source
“addition of telmisartan to standard therapies significantly reduces all-cause mortality, cardiovascular death, and heart failure hospital stays in hemodialysis patients with CHF and LVEF ≤ 40%.”
Cice G et al. Telmisartan added to ACE inhibitors in hemodialysis patients with CHF. J Am Coll Cardiol 2010 (PMID 21070920, abstract) (2010)· Abstract (Conclusions) Source
“CONCLUSIONS: BP-lowering treatment with an ARB did not significantly lower the risks of major cardiovascular events or death among patients with hypertension on chronic HD.”
Iseki K, et al. (OCTOPUS) Effects of ARB on mortality and cardiovascular outcomes in patients with long-term haemodialysis: a randomized controlled trial. Nephrol Dial Transplant 2013;28:1579-89 (PubMed abstract, PMID 23355629) (2013)· Abstract (Conclusions) Source

Starting doses (candesartan, valsartan) and losartan target above the US label maximum

“The recommended starting dose of Diovan is 40 mg twice daily. Uptitrate to 80 mg and 160 mg twice daily or to the highest dose tolerated by the patient.”
DIOVAN (valsartan) PI, Novartis (2026)· Section 2.4 Heart Failure Source
“Valsartan 20–40 mg once daily 160 mg twice daily 254 mg total daily”
2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure (2022)· p. 52, Table 13 Source
“Candesartan 4–8 mg once daily 32 mg once daily 24 mg total daily”
2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure (2022)· p. 52, Table 13 Source
“The dosage can be increased to a maximum dose of 100 mg once daily as needed to control blood pressure [see Clinical Studies (14.1)].”
COZAAR (losartan potassium) tablets, prescribing information, Organon LLC (2026)· Section 2.1 Hypertension Source
“Losartan (12.5) 25–50 mg o.d. 150 mg o.d.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 36, Table 11 Source

ARB added to an ACE inhibitor

“ATACAND also has an added effect on these outcomes when used with an ACE inhibitor [see Drug Interactions (7.4)].”
ATACAND (candesartan) PI, ANI (2025)· Section 1.2 Heart Failure Source
“Thus, there is little evidence of further clinical benefit when valsartan is added to an adequate dose of ACE inhibitor.”
DIOVAN (valsartan) PI, Novartis (2026)· Section 14.2 Heart Failure Source
“Combined use of an ARB with an ACEI is not recommended in patients with CKD as the risk of AKI and severe hyperkalaemia outweighs any added cardiorenal benefits.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 31, Recommendation Table 12 (Class III) Source

Open questions

CKD G5 (not on dialysis) initiation: set to 'not-recommended' (conservative; ESC CVD-CKD no data, ESC HF Table S4 stop rule at eGFR <20, ESC HF temporary discontinuation at eGFR <15). KDIGO 2024/Mullens would allow cautious use; owner to confirm.
Dialysis: proposed 'caution' for both initiate and continue based on labels (no contraindication, not dialysed) and small HD RCTs; ESC CVD-CKD says no supporting data. Owner may prefer 'no-data'.
KDIGO 2026 HF Figure 4 lists no ACEi/ARB/ARNI for HFrEF with eGFR 15-29 and Table 2 (HF guidance) uses creatinine <2.5 mg/dL or eGFR >30, unlike ESC CVD-CKD IIb for 15-29. Decide whether the engine shows G4 initiation as caution (proposed) or not-recommended.
Losartan: no FDA HF indication; HEAAL target 150 mg exceeds the US label maximum (100 mg). Show an off-label badge?
Trial renal exclusions: CHARM serum creatinine >3 mg/dL is quoted from the FDA label. Val-HeFT and HEAAL creatinine cutoffs come only from review tables that the PDF extraction scrambled (Mullens 2022 Table 1 suggests Cr >2.5 mg/dL for both; Beldhuis 2022 Fig 2B pairs Val-HeFT with >3.4), so they are not quoted. Primary papers (NEJM 2001, Lancet 2009) are paywalled.
ESC CVD-CKD Figure 12 footnote equates 300 umol/L with 'around 2.5 mg/dL' (300 umol/L is about 3.4 mg/dL); use with care if adopted as a threshold.
Transplant: only a KDIGO hypertension recommendation (ARB or CCB first-line); no HF-specific data. Proposed 'allowed' and apply graft-eGFR rules.