Angiotensin Converting Enzyme Inhibitors (ACEI) / Angiotensin Receptor Blockers (ARBS)* Heart Failure Medication Initiation and Titration

Bilateral renal artery stenosis NO Moderate/Severe aortic stenosis Considerations: • Baseline cough (ACEi) Hyperkalemia: K+ > 5.2 mmol/L See dosing Symptomatic HF • K+ supplements or LVEF < 40% Renal Dysfunction:Serum creatinine >220 µmol/L • K+ sparing diuretics Hypotension: SBP < 90 mmHg or symptoms YES Refer to • MRA See monitoring

Initiation Allergy: angioedema, hives, rash Physician • NSAIDS/COX2 inhibitors section Intolerance: cough (ACEi)

Titrate every 1-3 weeks, Volume Reduce/hold diuretic x 2-3 days No improvement, hold/reduce depending on tolerance deplete ACEI/ARB x 1-2 wks & reassess Reassess diuretic dose/other Hypotension Fluid non-essential BP lowering meds Goal: Target dose(see Euvolemic SBP<90mmHg Assessment Consider staggering doses dosing) or maximum with symptoms* Reduce/hold dose of other See Diuretic Reassess

Titration * Watch for trends Volume tolerated dose vasodilators algorithm 1-2 wks overload +/- ACEI/ARB x 1-2 weeks

Stop K+ supplements, reduce/ Serum K+ in 3-5 days, Considerations: • BP K+ 5.2-5.5 hold MRA (if applicable) Reassess ACEI/ARB dose • Dietary K+ • K+ supplements Stop K+ supplements, MRA. Serum K+ in 2-3 days, • K + Hyperkalemia • K+ sparing diuretics K+ 5.6-6.0 hold ACEI/ARB Reassess ACEI/ARB dose K+ > 5.2 mmol/L* • MRA Assess * Watch for trends • Renal dysfunction Treat hyperkalemia • Scr K+ > 6.0 Refer to MD/NP +/- send to ED

Reduce/hold diuretic Scr in Considerations: Volume deplete x 2-3 days 5-7 days • Addition of Renal nephro-toxic drugs: dysfunction Fluid Hold Scr in Rechallenge NSAIDS/COX2 Assessment Euvolemic ACEI/ARB 5-7 days at lower dose >30% in serum • Worsening HF creatinine* • Co-morbidity: DM, Volume Increase diuretic per * Watch for trends dehydration, CKD Diuretic algorithm; Scr in overload reduce/hold of ACEI/ARB 2-3 days

Other Considerations: Initiation of Blood Serum Serum **

ACEI/ARB Pressure Creatinine Potassium Angioedema: Cough: • Stop ACEI/ARB contact • Assess at baseline as may be due to One week after: One week after: • Baseline Scr / GFR • Every visit physician; refer to ED worsening HF 1. initiation 1. initiation • Baseline K+ - Siting • Do not rechallenge • If intractable cough secondary to ACEI 2. dosage increase* 2. dosage increase* • Baseline blood pressure - Standing • Caution when substituting consider: 3. > 30% ↑ in Scr - +/- lying ARB for ACEI - Trial of another ACEI or lower dose * Obtain baseline value prior to any - Switch to ARB up-titration or change in symptom status

Monitoring • Reassess in 2 weeks and document If stable: Q 3-6 months

* This algorithm is intended for single agent (ACEI or ARB) ** This is a guide to monitoring; increase monitoring may be required given patient’s status and co-morbidities (ie. renal insufficiency) December 2018 **This is a guide to monitoring; increase monitoring may berequired given patient’s status and co-morbidities *verapamil and diltiazem are contraindicated in systolic heart failure (EF <40%) Monitoring ** Assess Titration Initiation • • BP Status • Rate tolerated dose dosing) ormaximum Goal: depending ontolerance Titrate every 2-4weeks, LVEF <40% Fluid Heart • Baselinebloodpressure • Baselineheartrate • BaselineECG Target dose(see Beta-Blocker Initiation Intolerance orallergy Acute decompensated heartfailure Asthma Hypotension: 2nd or3rd degree AV blockwithoutapacemaker Bradycardia: (>0.24 msec) Bifascicular block,PRinterval prolongation HR< 60bpmorsymptomatic SBP <90mmhgorsymptoms with symptoms with symptoms SBP<90mmHg HR <55bpm Bradycardia Hypotension overload - - - • Every visit Volume Blood Pressure +/- lying Standing Siting Heart Failure MedicationInitiationandTitration • • OtherBPlowering retention: • - Ivabradine - digoxin - amiodarone - sotalol - diltiazem, verapamil - diuretics - ACEI/ARB/ARNI hydralazine, CCB) - vasodilators (nitrates, - Worsening HF - Co-morbidity - Nonadherence - Salt/fluidintake - NSAIDS/COX2, glitazones Beta -Blockers Other rate controlling drugs: Other precipitants offluid YES Considerations: Considerations: Considerations: • ECG asclinically indicated: • Every visit

- - Δ insymptom status after eachup-titration Heart Rate NO drugs: Physician Refer to Volume overload intheabsence ofPPM • • • Conduction Abnormality: Volume deplete severe symptoms

Mild symptoms 2nd or3rd degree AV block PR interval prolongation Bifascicular block Moderate to Euvolemic • Otherrate controlling drugs: • COPD withreversible component - digoxin - sotalol - amiodarone - verapamil, diltiazem - ivabradine dailyweights instructed to perform • Patient shouldbe • Every visit Weight Status Fluids/ Considerations:

See below (volume overload) Consider staggering doses other BPlowering drugs. Reassess diuretic dose, x 2-3days Reduce/hold diuretic

• • • • • • Sodium/fluid restriction Increase diuretic Maintain BBdose Sodium/fluid restriction Increase diuretic Consider reducing BBdose YES NO (othercauses ruledout): • Extreme limiting fatigue 1-2weeks doseofBB, review in - could consider decreasing Reassess in1-2weeks Consider decreasing BBdose. Consider referral to Cardiologist Stop BB Other See monitoring December 2018 See dosing section 1-2 wks reassess hold/reduce BBx No improvement, see diuretic algorithm

** This isaguide to monitoring; increase monitoring may berequired given patient’s status and co-morbidities (ie. renalinsufficiency) Monitoring ** Assess Titration Initiation • • maximum tolerated dose (see dosingbelow) or Goal: tolerance Titrate monthly dependingon BB andLVEF <40% on ACEI/ARB orARNI+ failure (NYHAII-IV) Symptomatic heart • BaselineK+ • BaselineScr/GFR Initiation ofMRA SCr K+ Target dose othermedications affecting potassium/serum creatinine • Withdehydration, illness,change in symptom status orchange in • 1week post up-titration ofMRA • Priorto up-titration ofMRA • After initiation: 3 days, 1 week, 4 weeks, then monthly x3 Serum Creatinine Intolerance orallergy clearance <30ml/min µmol/Loracreatinine Renal Dysfunction: Hyperkalemia: * * > 30%↑inSCr Watch for trends K+ >5.2mmol/L Watch for trends Hyperkalemia Dysfunction Renal K+ >5.2mmol/L Heart Failure MedicationInitiationandTitration Mineralocorticoid ReceptorAntagonists(MRA) Serum creatinine >220 Serum Potassium • GIloss • ACEI/ARB orARNI NSAIDS/COX2 nephrotoxic drugs: • Additionof • Renal dysfunction • ACEI/ARB orARNI • Dietary K+ • K+sparingdiuretics • K+supplements YES Considerations: Considerations: NO Physician Refer to

Gynecomastia (4-5%ofmales)withspironolactone. Consider switching to Eplerenone. Other considerations: patients may have their doseincreased to 50mgwithclosemonitoring. of hyperkalemia shouldbeinitiated on12.5mgdailyandtitrated as tolerated. Some The usualdoseis25mgdaily, however, thosewithpoorrenal functionand/or ahistory Dosing: Assessment

Other

Fluid K+ 5.2-5.5 K+ >5.5 • ACEI/ARB orARNI • NSAIDS/COX2 inhibitors • K+sparingdiuretics • K+supplements Considerations: Euvolemic overload Volume Volume deplete then reduce/hold MRA changes inK+dietary intake, dietitian consult.Ifnomajor Stop K+supplements, Treat hyperkalemia asrequired Refer to physician/NP Reduce/hold ACE/ARB orARNI Hold MRA Stop K+supplements, algorithm Refer to diuretic MRA Reduce/hold MRA Reduce/hold days diuretic x2-3 Reduce/hold 2-3 days Scr in 5-7 days Scr in 5-7 days Scr in See monitoring See dosing December 2018 section in 2-3days Serum K+ in 3-5days Serum K+ at lower dose re-challenge Consider ** This isaguideto monitoring; increase monitoring may berequired given patient’s status and co-morbidities (ie. renalinsufficiency) Monitoring ** Assess Titration Initiation Symptomatic HF • Scr • K+ • BP tolerated dose dosing) ormaximum Goal: depending ontolerance Titrate every 3-6weeks, LVEF <40% therapy and B-blocker despite ACEI/ARB • Baselinebloodpressure • BaselineK+ • BaselineScr/GFR Target dose(see Initiation ARNI ARNI (AngiotensinReceptorblocker/NeprilysinInhibitors[Sacubutril/Valsartan]) Allergy: Hypotension: Renal Dysfunction: Hyperkalemia: Moderate/Severe aortic stenosis Bilateral renal artery stenosis angioedema, hives, rash * * * Watch for trends >30% inserum K+ >5.2mmol/L Watch for trends with symptoms Watch for trends SBP<90mmHg Hyperkalemia SBP <90mmhgorsymptoms dysfunction Hypotension creatinine K+ >5.2mmol/L • Every visit Renal GFR <30ml/min Blood Pressure Heart Failure MedicationInitiationandTitration

• Co-morbidity • Worsening HF COX2) toxic drugs(NSAIDS/ • Additionofnephro- • Renal Dysfunction • MRA • K+sparingdiuretics • K+supplements • Dietary K+ Assessment YES Considerations: 3. 2. 1. One week after: Considerations: Fluid > 30%↑inScr dosage increase* initiation Creatinine Serum NO up-titration orchange in symptom status * Physician Refer to Obtain baselinevalue priorto any If stable:

Euvolemic overload Volume deplete Volume Q 3-6months Assessment K+ 5.2-5.5 K+ 5.6-6.0 K+ >6.0 Fluid 2. 1. One week after: • • • NSAIDS/COX2 inhibitors • MRA • K+sparingdiuretics • K+supplements Stop ARBandstart following day Stop ACEI x36hrpriorto start dosage increase* initiation +/- ARNIx1-2weeks vasodilators Reduce/hold doseofother Reassess diuretic dose/vasodilator Reduce/hold diuretic x2-3days Potassium Serum Considerations: Refer to Physician, +/-ED Treat hyperkalemia, hold ARNI Stop K+supplements, MRA, reduce/hold MRA Stop K+supplements, Euvolemic overload Volume deplete Volume Other Considerations: reduce/hold ofARNI Increase diuretic; ARNI Hold Reduce/hold diuretic • Donotre-challenge physician, refer to ED • Stop ARNI,contact x 2-3days ARNI x1-2wks &reassess No improvement, hold/reduce Angioedema: See Diuretic algorithm 5-7 days Scr in Reassess ARNIdose Serum K+in2-3days, Reassess ARNIdose Serum K+in3-5days, See monitoring See dosing December 2018 section 2-3 days Scr in at lower dose Rechallenge 5-7 days Scr in 1-2 wks Reassess **This is a guide to monitoring; increase monitoring may berequired given patient’s status and co-morbidities *verapamil and diltiazem are contraindicated in systolic heart failure (EF <40%),these drug also increase IVA levels through CYP3Ainhibition Monitoring ** Assess Titration Initiation Titrate every 2-4weeks, rhythm Normal sinus tolerate BB on maximally HR ≥70bpm HF symptoms LVEF <40%+ Rate Heart 50-60bpm Goal: depending ontolerance • Baselineheartrate • BaselineECG Heartrate Initiation of IVA

2°or 3°AV block,SSS,SA block Pacemaker dependence Ventricular arrhythmia Intolerance orallergy Atrial arrhythmia Prolonged QT with symptoms HR <50bpm Bradycardia • ECG asclinically indicated: • Every visit - Δinsymptom status - after eachup-titration Heart Failure MedicationInitiationandTitration Heart Rate over beta-blocker dose. Note: • YES Ivabradine (IVA) - digoxin - amiodarone - sotalol - diltiazem, verapamil Other rate controlling drugs: IVA dose shouldbe Considerations: • May ↑riskofatrial fibrillation • Transient visualchanges NO Other Physician Refer to ↓

• •

2° or3°degree AV block Bi-fascicular block - 1°AV block - incombo withQT prolonging drugs Caution: - sotalol - amiodarone - CCB*:verapamil, diltiazem Other rate controlling drugs: - Druginteractions: 3A4substrate Abnormality ? Conduction Considerations: - digoxin - beta-blockers YES NO Reassess intwo weeks Consider decreasing IVA dose Consider referral to Cardiologist Stop IVA See monitoring December 2018 See dosing section ** Weight gain: 2-3lbs in1-2days or5lbs in 1week ** This isaguide to monitoring; increased monitoring may berequired given patient’s status and co-morbidities Monitoring ** Assess Titration Initiation • • • • achieve euvolemia Goal: according to symptoms Titrate reassessed eachvisit dose shouldbe fluid overload symptoms of with signsand Heart failure

SCr K+ Blood Pressure Fluid Status • Baselinebloodpressure • BaselineK+ • BaselineScr/GFR Minimumdoseto up, down ormaintain Initiation of Diuretic Pulmonary edema:rales,Pulmonary crackles, CXR Peripheral pittingedema Recent weight gain** Worsening SOBOE Worsening /new SOB

* * serum creatinine Fluid Assessment K+<3.5 mmol/L* Watch for trends Watch for trends with symptoms SBP<90mmHg Hypokalemia dysfunction Hypotension >30 %↑in to perform dailyweights • Patient shouldbeinstructed • Every visit Renal Fluid/Weight Heart Failure MedicationInitiationandTitration Assessment Hepatojugular reflex JVP assessment-JVD Sacral edema/Ascites Orthopnea/PND

• GIlosses • Worsening HF NSAIDS, COX2 • Nephrotoxic drugs: • MRA ACEI/ARB/ARNI • Additionof Fluid Assessment • • • ACEI/ARB/ARNI • • GI loss Renal function MRA Addition of K+ supplementation 3. 30%↑inSCr 2. dosage increase** 1. initiation One week after: Considerations: Considerations: Diuretics Creatinine Serum up-titration orΔin symptom status ** Obtain baselinevalue prior to any diuretic use • dysfunction • (<2gm/d) • • Assessment History ofpast Underlying renal Sodium restriction Fluid restriction Supplementation Volume overload Volume deplete Consider K+ Fluid Euvolemic 2. dosage increase** 1. initiation One week after: Considerations: Potassium Serum Co-morbidity • • BBdose glitazones, increase NSAIDs,COX2 • • Worsening HF/ Sodium load Other precipitants: Non-adherence Euvolemic overload Volume Volume deplete ACEI/ARB/ARNI x1-2wks, ↑ diuretic as dose tolerated Reduce/hold doseofothervasodilators +/- affecting BP Decrease diuretics/stagger doseof R dose in3-7days Reduce/hold diuretic x2-3days & reassess maintenance eassess diuretic dose/vasodilators Assessment

Fluid

↑ diuretic doseas tolerated ACEI/ARB/ARNI, dose MRAfirst; then Consider reduce/hold diuretic dose Reassess diuretic x2-3days Reduce/hold - - - • Every visit Blood Pressure +/- lying Standing Siting

See monitoring other medications See dosing December 2018 section diuretic dose Reassess 2-3 days Scr in 5-7 days Scr in