B-QuiCK: Heart Failure

ACE inhibitor

Conventional approach:
Gradual increases to maintenance dose; in general, doubling dose no sooner than every two to four weeks

Assertive approach:
Guidelines now indicate that up-titration every one to two weeks is reasonable, but rapid titration should only occur with close supervision

Some treatment protocols recommend switching to ARNI after achieving mid-range ACE inhibitor or ARB dose (see below)

• Systolic blood pressure is ≥ 100 mmHg
• Serum potassium is < 5.5 mmol/L; significant caution is still required between 5.0 – 5.5 mmol/L
• Creatinine is < 250 micromol/L or eGFR is ≥ 30 mL/min/1.73 m² (seek cardiology advice if not)
• In general, discontinue potassium supplements and potassium-sparing diuretics before introducing an ACE inhibitor
• ACE inhibitor contraindicated in patients with history of idiopathic or hereditary angioedema

• Check serum potassium and creatinine^† one week after first dose
• Check blood pressure, serum potassium and creatinine prior to each dose increase; delay dose increase or seek cardiologist advice if systolic blood pressure is < 95 mmHg, serum potassium is > 5.5 mmol/L or creatinine is > 25% above baseline
• Regular physical examination: weight, pulse, jugular venous pressure, chest auscultation
• Once stable dosing is achieved, continue long-term and monitor every three months (or more frequently if required depending on the patient)

Enalapril

2.5 mg, once or twice daily

10 – 20 mg, twice daily (higher doses indicated in some patients, e.g. those with hypertension). Once stabilised, total daily dose can be given once daily, if tolerated.

Quinapril

2.5 – 5 mg, twice daily

20 – 40 mg, daily, in 1 – 2 divided doses (higher doses indicated in some patients, e.g. those with hypertension)

Lisinopril

2.5 mg, once daily

20 – 40 mg, once daily

Perindopril

2 mg, once daily

4 mg, once daily

Ramipril^**

1.25 mg, once daily

10 mg daily, preferably taken in two divided doses

ARB

Candesartan

4 mg, once daily

32 mg, once daily

Losartan

12.5 mg, once daily

150 mg, once daily

ARNI^‡

Sacubitril/valsartan

• 49 mg/51 mg, twice daily, for most patients
• 24 mg/26 mg, twice daily, may be suitable for higher risk patients (see main text)

97 mg/103 mg, twice daily

Increase dose every two weeks

• As for ACE inhibitor/ARB (above)
• Patient has stopped taking an ACE inhibitor/ARB
• It has been at least 36 hours since last ACE inhibitor dose or at least 24 hours since last ARB dose

Beta blocker

Carvedilol

3.125 mg, twice daily

25 mg, twice daily, for patients weighing < 85 kg or 50 mg, twice daily, for patients weighing ≥ 85 kg

Conventional approach:
Gradual increases to maintenance dose; in general, doubling dose no sooner than every two to four weeks

Assertive guideline approach:
Increase dose every two weeks until maximum tolerated or target dose is reached (ensure appropriate monitoring occurs at each dose increase)

• Symptoms of fluid overload have resolved and there are no symptoms of worsening heart failure
• No symptomatic bradycardia, hypotension or second- or third-degree heart block

• As for ACE inhibitor/ARB/ARNI above
• If the patient has first degree heart block (i.e. PR interval > 0.2 seconds), an ECG is recommended before each dose increase. If an ECG is not available, seek cardiology advice.

Bisoprolol

1.25 mg, once daily

10 mg, once daily

Metoprolol succinate (modified-release)

23.75 mg, once daily

190 mg, once daily

MRAs

Spironolactone

25 mg, once daily

50 mg, once daily

• Increase dose after two weeks

• eGFR is > 30 mL/min/1.73 m²
• Serum potassium is < 5.0 mmol/L

• Check creatinine and electrolytes regularly, i.e. at one week, one month and then at least six monthly

Eplerenone^‡

SGLT-2 inhibitor^‡

Empagliflozin

10 mg, once daily

Not applicable; continue treatment at 10 mg, once daily

• eGFR is > 20 mL/min/1.73 m²
• Patient does not have type 1 diabetes (due to risk of diabetic ketoacidosis)

• Assess renal function before initiation of concomitant medicines that may reduce renal function, then at least annually thereafter
• Warn patients about increased risk of Fournier’s gangrene (rare). Recommend patients self-check their genitals and surrounding skin regularly for changes in integrity, inflammation or signs of infection. Consider temporarily stopping treatment in patients with active genital or urinary tract infections until resolved.