If-channel inhibitor (ivabradine)
AMT in HFrEF · Class IIaRemoval 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.
- IvabradineLabel does not address dialysis removal
The ivabradine label contains no statement on dialysis; it has no data below a creatinine clearance of 15 mL/min.
“No data are available for patients with creatinine clearance below 15 mL/min”
Drugs and doses
| Drug | Brands | Start | Target | Kidney dosing |
|---|---|---|---|---|
| Ivabradine | Corlanor, Procoralan | 5 mg b.i.d. with food (2.5 mg b.i.d. if conduction defects or bradycardia could cause haemodynamic compromise; EMA/ACC also suggest 2.5 mg b.i.d. at age ≥75) | 7.5 mg b.i.d. (maximum); titrate every 2 weeks to resting HR 50–60 b.p.m. | No dose adjustment for CrCl 15–60 mL/min (only ~4% excreted unchanged in urine); no data below CrCl 15 mL/min or on dialysis. |
Status by kidney stage
| Stage | Initiate | Continue |
|---|---|---|
| G1 | Recommended Class IIa (ESC 2026) and FDA-labelled for LVEF ≤35%, sinus rhythm, resting HR ≥70 on maximally tolerated beta-blocker; no kidney restriction. | Recommended Continue while in sinus rhythm and HR tolerates; no kidney-related adjustment. |
| G2 | Recommended Same as G1; no dose adjustment. | Recommended Continue; no adjustment. |
| G3a | Recommended ESC CVD–CKD 2026 Class IIa for eGFR ≥20; label: no dose adjustment for CrCl 15–60. | Recommended Continue at usual HR-guided dose. |
| G3b | Recommended ESC CVD–CKD Class IIa (eGFR ≥20) and label permits without adjustment (CrCl 15–60). | Recommended Continue at usual HR-guided dose. |
| G4 | Allowed Label permits without dose change down to CrCl 15; ESC CVD–CKD Class IIa only for eGFR ≥20, so eGFR 15–19 is outside guideline support; trial data sparse. | Allowed May be continued; no renal dose adjustment; monitor HR. |
| G5 | Not recommended No data below CrCl 15 (FDA/EMA); EMA says use with precaution; ESC 2021 practical guidance listed CrCl <15 as a contraindication. Conservative choice: do not initiate. | No data No data: the FDA label has no data below CrCl 15 and the EU label advises precaution; no dialysis outcome data. Individualize with nephrology input. |
| dialysis | Not recommended Not studied in outcome trials; a review advises against use in HFrEF with ESRD; only small single-arm HD series exist. | No data No data: the FDA label has no data below CrCl 15 and the EU label advises precaution; no dialysis outcome data. Individualize with nephrology input. |
| aki | No data No AKI-specific statement; ivabradine is contraindicated in acute decompensated HF and clinically significant hypotension, common AKI contexts. | No data No AKI-specific statement; renal clearance minimal, so AKI per se does not mandate a dose change; reassess if haemodynamically unstable. |
| transplant | No data No kidney-transplant-specific statement found. | No data No kidney-transplant-specific statement found. |
Cutoffs recorded from the sources
- hr < 70 bpm → contraindicated (initiate; ivabradine)“Resting heart rate below 70 beats per minute prior to treatment” — ema-ivabradine, SmPC 4.3 Contraindications, p. 4
- hr > 60 bpm → uptitrate (uptitrate; ivabradine)“> 60 bpm | Increase dose by 2.5 mg (given twice daily) up to a maximum dose of 7.5 mg twice daily” — fda-ivabradine, Section 2.1 Table 1
- hr between 50,60 bpm → maintain dose (continue; ivabradine)“50-60 bpm | Maintain dose” — fda-ivabradine, Section 2.1 Table 1
- hr < 50 bpm → reduce dose by 2.5 mg b.i.d.; stop if already 2.5 mg b.i.d. (dose_reduce; ivabradine)“< 50 bpm or signs and symptoms of bradycardia | Decrease dose by 2.5 mg (given twice daily); if current dose is 2.5 mg twice daily, discontinue therapy” — fda-ivabradine, Section 2.1 Table 1
- hr < 50 bpm → reduce or stop if persistent (hold; ivabradine)“Treatment must be reduced or stopped if resting heart rate decreases persistently below 50 b.p.m. or if symptoms of bradycardia occur” — esc2021-supp, p. 19, Supplementary Table 8
- sbp < 90 mmHg → contraindicated (initiate; ivabradine)“Ivabradine is contraindicated in patients with severe hypotension (blood pressure < 90/50 mmHg) (see section 4.3).” — ema-ivabradine, SmPC 4.4 Patients with hypotension, p. 6
- egfr < 20 mL/min/1.73m2 → caution (initiate; ivabradine)“Additional medical therapy with ivabradine should be considered in patients with eGFR ≥20 mL/min/1.73 m2 in sinus rhythm and heart rate >70 b.p.m. to reduce the risk of cardiovascular death or HF hospitalization.” — esc2026-ckd, p. 37
- egfr < 15 mL/min (creatinine clearance) → not-recommended (initiate; ivabradine)“No dosage adjustment is required for patients with creatinine clearance 15 to 60 mL/min. No data are available for patients with creatinine clearance below 15 mL/min” — fda-ivabradine, Section 8.7 Renal Impairment
- other > 35 % → not indicated (initiate; ivabradine)“Ivabradine should be considered for patients with symptomatic HFrEF, LVEF ≤35%, in sinus rhythm, resting heart rate >70 b.p.m., on the highest tolerated ACE-I/ARNI, MRA, SGLT2-I, and beta-blockers to reduce the risk of HFH or CV death” — esc2026, p. 38
Trial evidence (informational)
- SHIFT · HFrEF, LVEF ≤35%, sinus rhythm, HR ≥70, HF hospitalisation within 12 monthsHF hospitalisation or CV death: HR 0.82 (95% CI 0.75–0.90); driven by HF hospitalisation, no CV death benefit“SHIFT demonstrated that Corlanor reduced the risk of the combined endpoint of hospitalization for worsening heart failure or cardiovascular death based on a time-to-event analysis (hazard ratio: 0.82, 95% confidence interval [CI]: 0.75, 0.90, p < 0.0001) (Table 3).” — fda-ivabradine, Section 14.1 SHIFT
- SHIFT · as abovemortality component: no favourable effect on CV death“The treatment effect reflected only a reduction in the risk of hospitalization for worsening heart failure; there was no favorable effect on the mortality component of the primary endpoint.” — fda-ivabradine, Section 14.1 SHIFT
- SHIFT (beta-blocker dose subgroups) · as aboveprimary endpoint by beta-blocker dose: little if any benefit at target beta-blocker doses“Corlanor’s benefit on the primary endpoint in SHIFT appeared to decrease as the dose of beta-blockers increased, with little if any benefit demonstrated in patients taking guideline-defined target doses of beta-blockers.” — fda-ivabradine, Section 14.1 SHIFT
Acute kidney injury
No source addresses ivabradine in AKI. Renal clearance is minor, so no renal dose change is needed, but the drug is contraindicated in acute decompensated HF and clinically significant hypotension.
“Corlanor is contraindicated in patients with: • Acute decompensated heart failure • Clinically significant hypotension”
“A sub-analysis from the SHIFT trial indicated that ivabradine is equally effective in reducing the primary endpoint of HF hospitalization and cardiovascular death in patients with or without renal dysfunction.”
Dialysis
No label or guideline data. One review discourages use in HFrEF with ESRD; small HD series (18-patient open-label study; CARVIVA-HF) suggest HR reduction and less intradialytic hypotension without outcome data.
Trials: CARVIVA-HF (small, haemodialysis, cited by Inampudi 2018), Kawasaki 2024 open-label HD study (n=18)
“Due to small sample size and lack of studies with hard outcomes such as HF mortality and hospitalization, the use of ivabradine is not encouraged in patients with HFrEF and ESRD until further evidence is available.”
Inampudi C, Alvarez P, Asleh R, Briasoulis A. Therapeutic approach to patients with heart failure with reduced ejection fraction and end-stage renal disease. Curr Cardiol Rev 2018 (2018)· Section 7 Ivabradine Source“Ivabradine hydrochloride improved dialysis-related hypotension.”
Kawasaki S, et al. The efficacy and safety of ivabradine hydrochloride in hemodialysis patients with chronic heart failure. Ther Apher Dial 2024 (abstract, Europe PMC record PMID 38199237) (2024)· Abstract Source“No dosage adjustment is required for patients with creatinine clearance 15 to 60 mL/min. No data are available for patients with creatinine clearance below 15 mL/min”
“No data are available in patients with creatinine clearance below 15 ml/min. Ivabradine should therefore be used with precaution in this population.”
“Additional medical therapy with ivabradine should be considered in patients with eGFR ≥20 mL/min/1.73 m2 in sinus rhythm and heart rate >70 b.p.m. to reduce the risk of cardiovascular death or HF hospitalization.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 37, Section 6.2.2.1.5 Source
Kidney transplant
No kidney-transplant-specific statement found. Watch CYP3A4 interactions (strong inhibitors contraindicated).
No verbatim statement found for this cell.
Albuminuria
No source differentiates ivabradine use by albuminuria category.
No verbatim statement found for this cell.
Monitoring
Reassess resting HR after 2 weeks and with each titration (target 50–60 b.p.m.); monitor rhythm for AF (stop if persistent AF); watch bradycardia with other negative chronotropes (digoxin, amiodarone, beta-blockers).
“Regularly monitor cardiac rhythm. Discontinue Corlanor if atrial fibrillation develops.”
“The risk of bradycardia increases with concomitant administration of drugs that slow heart rate (e.g., digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking Corlanor with other negative chronotropes.”
“If a patient develops persistent/continuous AF during therapy with ivabradine, the drug should be stopped.”
In-hospital initiation
Do not start in acute/unstable HF; ESC 2026 advises considering down-titration or discontinuation in advanced HFrEF with hypoperfusion.
“Heart failure must be stable before considering ivabradine treatment.”
Procoralan (ivabradine) EPAR product information (SmPC), Les Laboratoires Servier (2026)· SmPC 4.4 Chronic heart failure, p. 5 Source“Down-titration or discontinuation of beta-blockers or ivabradine should be considered in selected patients with advanced HFrEF and evidence of organ hypoperfusion, despite initial treatment, to increase cardiac output and improve symptoms.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 12 (new recommendations list; full rec table on p. 54) Source“New Class IIa: Downtitration or discontinuation of beta-blockers or ivabradine should be considered in selected patients with advanced HFrEF and evidence of organ hypoperfusion, despite initial treatment, to increase cardiac output and improve symptoms.”
2026 ESC HF Guideline lecture slides (2026)· slide 61
Outpatient
Start in stable outpatients only after beta-blocker optimisation; SHIFT required HF hospitalisation within 12 months (ESC text: 'recent HFH').
“As beta-blockers have well-proven morbidity and mortality benefits, they should be initiated and uptitrated to target doses first, before assessing the resting heart rate for consideration of adding ivabradine.”
“Patients had to have been hospitalized for heart failure within 12 months prior to study entry.”
Where sources disagree
Resting heart-rate threshold for initiation (≥70 vs >70 vs ≥75)
“Corlanor is indicated to reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction ≤ 35%, who are in sinus rhythm with resting heart rate ≥ 70 beats per minute and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use.”
“Ivabradine should be considered in patients with symptomatic HFrEF who at rest are in sinus rhythm with heart rate ≥70 b.p.m., LVEF ≤35%, and recent HFH, despite stable FMT including optimized beta-blocker therapy.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 34, Section 6.1.5.1 Source“Ivabradine should be considered for patients with symptomatic HFrEF, LVEF ≤35%, in sinus rhythm, resting heart rate >70 b.p.m., on the highest tolerated ACE-I/ARNI, MRA, SGLT2-I, and beta-blockers to reduce the risk of HFH or CV death”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 38, Recommendation Table 5 Source“Ivabradine should be considered in patients with HFrEF in sinus rhythm with heart rate >70 b.p.m. despite beta-blockers at the highest tolerated dose or if beta-blockers are contraindicated.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 60, Section 9.2 Source“Ivabradine is indicated in chronic heart failure NYHA II to IV class with systolic dysfunction, in adult patients in sinus rhythm and whose heart rate is ≥ 75 bpm, in combination with standard therapy including beta-blocker therapy or when beta-blocker therapy is contraindicated or not tolerated”
Procoralan (ivabradine) EPAR product information (SmPC), Les Laboratoires Servier (2026)· SmPC 4.1, p. 3 Source
Tool uses fda-ivabradine: Label > guideline; FDA ≥70 also matches SHIFT entry criterion and ESC 2026 text (Section 6.1.5.1). ESC rec table/Section 9.2/CVD–CKD use >70; EMA restricts to ≥75. Make default ≥70 user-adjustable.
Use at CrCl/eGFR <15 (G5) and dialysis
“No dosage adjustment is required for patients with creatinine clearance 15 to 60 mL/min. No data are available for patients with creatinine clearance below 15 mL/min”
“No data are available in patients with creatinine clearance below 15 ml/min. Ivabradine should therefore be used with precaution in this population.”
Procoralan (ivabradine) EPAR product information (SmPC), Les Laboratoires Servier (2026)· SmPC 4.2 Renal impairment, p. 4 Source“Severe liver dysfunction or renal dysfunction (no evidence on safety or pharmacokinetics for creatinine clearance <15 mL/min).”
2021 ESC HF Guidelines Supplementary Data (2021)· p. 18, Supplementary Table 8 (Contraindications) Source“Due to small sample size and lack of studies with hard outcomes such as HF mortality and hospitalization, the use of ivabradine is not encouraged in patients with HFrEF and ESRD until further evidence is available.”
Inampudi C, Alvarez P, Asleh R, Briasoulis A. Therapeutic approach to patients with heart failure with reduced ejection fraction and end-stage renal disease. Curr Cardiol Rev 2018 (2018)· Section 7 Ivabradine Source
Tool uses esc2021-supp: FDA only says 'no data'. Following the brief's 'more conservative option' rule, the matrix uses not-recommended for initiation and caution for continuation; show all four quotes.
Lower eGFR bound for recommendation (ESC CVD–CKD ≥20 vs label CrCl ≥15)
“Additional medical therapy with ivabradined should be considered in patients with HFrEF and CKD with eGFR ≥20 mL/min/1.73 m2 to reduce the risk of cardiovascular and HF-related events.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 40, Recommendation Table 15 Source“No dose adjustment is required in patients with renal insufficiency and creatinine clearance above 15 ml/min (see section 5.2).”
Procoralan (ivabradine) EPAR product information (SmPC), Les Laboratoires Servier (2026)· SmPC 4.2 Renal impairment, p. 3 Source
Tool uses fda-ivabradine: Label governs permissibility (CrCl ≥15, no adjustment); ESC CVD–CKD ≥20 governs recommendation strength, so eGFR 15–19 shown as 'allowed/caution'.
Starting dose in older patients
“In patients with a history of conduction defects or other patients in whom bradycardia could lead to hemodynamic compromise, initiate therapy at 2.5 mg twice daily before increasing the dose based on heart rate”
“History of conduction defects Age $75 y 2.5 mg twice daily with meals”
“Ivabradine 5 mg b.i.d. 7.5 mg b.i.d.”
Tool uses fda-ivabradine: Label > guideline; display ACC/EMA age ≥75 option as a note ('$75' in ACC text is a PDF artefact for ≥75).
Open questions
- Default HR threshold: FDA ≥70 vs ESC rec table >70 (and EMA ≥75). Proposed ≥70, user-adjustable.
- G5/dialysis: FDA says only 'no data'; we chose not-recommended (initiate) on the conservative rule. Owner to confirm or relax to caution.
- ESC 2026 text requires 'recent HFH' but the recommendation table does not; should the tool ask about HF hospitalisation within 12 months?