Prescribing Guidelines for HEART FAILURE

This guidance is not intended to replace NICE CG108 Chronic heart failure (Aug‑10), but provides primary care prescribers with a summary of key points relevant in practice.

 

Aims of treatment

  • To relieve symptoms
  • To improve exercise tolerance
  • To reduce incidence of acute exacerbations
  • To reduce hospitalisations
  • To reduce mortality

 

First-line treatment

Offer both angiotensin-converting enzyme (ACE) inhibitors and beta-blockers licensed for heart failure, to all patients with heart failure due to left ventricular systolic dysfunction (LVSD). Clinical judgement should guide which drug to start first.

 

ACE Inhibitors (first-line treatment)

An ACE inhibitor is recommended for ALL patients with asymptomatic LVSD or symptomatic heart failure (unless contra- indicated).

Start with a low dose and titrate upwards at short intervals (e.g. not less than 2 weeks). Where possible, ACE inhibitor treatment should be titrated up to the highest licensed dose which is tolerated. GPs considering initiating ACE inhibitor therapy should consider specialist supervision and/or particularly careful monitoring for those patients:

  • receiving multiple or high dose diuretics (≥ furosemide 80mg)
  • with hypovolaemia
  • with hyponatraemia (<130mmol/l)
  • with pre-existing hypotension (systolic < 90mm Hg)
  • with unstable heart failure
  • with renal impairment (creatinine > 150mmol/l)
  • receiving high-dose vasoldilator therapy
  • aged 70 years or more

NB: A small dose of an ACE inhibitor is better than no ACE inhibitor at all.

Because of the risk of hypotension, especially in patients with hypovolaemia, consideration should be given to withholding or reducing the dose of diuretics for 24 hours prior to commencement of an ACE inhibitor. Where possible all ACE inhibitors should be used in a single daily dose to aid compliance and cost-effectiveness.

Formulary recommended ACE inhibitors;

  • LISINOPRIL initially 2.5-5mg ONCE DAILY, titrated up to 30-35mg ONCE DAILY, or
  • RAMIPRIL initially 2.5mg ONCE DAILY (1.25mg if already prescribed a diuretic), titrated up to 10mg ONCE DAILY

Monitoring: serum urea, creatinine, electrolytes and eGFR at initiation and after each dose increment

 

Beta-blockers (first-line treatment)

Offer beta-blockers licensed for heart failure to all patients with heart failure due to left ventricular systolic dysfunction, including:

  • older adults and
  • patients with:
    • peripheral vascular disease
    • erectile dysfunction
    • diabetes mellitus
    • interstitial pulmonary disease and
    • chronic obstructive pulmonary disease (COPD) without reversibility.

Beta-blocker therapy should be initiated by those experienced in the management of heart failure and should commence at a very low dose and titrated up by doubling doses at intervals of not less than two weeks. Heart rate, blood pressure and clinical status should be assessed after each titration. Symptoms may deteriorate initially, calling for adjustment of concomitant therapy, such as temporary increase in dose of diuretics.

Stable patients who are already taking a beta-blocker for a comorbidity (for example, angina or hypertension), and who develop heart failure due to left ventricular systolic dysfunction, should be switched to a beta-blocker licensed for heart failure.

Formulary recommended beta-blocker for heart failure;

  • BISOPROLOL initially 1.25mg ONCE DAILY, titrated according to response and tolerability to 10mg ONCE DAILY

Where an alternative to bisoprolol is required, for example where there is intolerance or concern that unopposed beta-blockade may be undesirable;

Carvedilol should be considered as the appropriate alternative beta-blocker for heart-failure patients. There is also a stronger evidence base for carvedilol in those patients with higher grades of heart failure and its use may be preferred in this situation. Prescribers should be aware that carvedilol requires twice-daily dosing and the implications of this for compliance with therapy should be taken into account when selecting a beta-blocker for heart failure.

NB. Although doses of beta-blockers should be titrated to the maximum tolerated, a small dose of a beta-blocker is better than no beta-blocker at all.

 

Second-line treatment

Seek specialist advice and consider adding one of the following if a patient remains symptomatic despite optimal therapy with an ACE inhibitor and a beta-blocker:

  • an aldosterone antagonist licensed for heart failure (especially if the patient has moderate to severe heart failure [NYHA class III–IV] or has had an MI within the past month) or
  • an angiotensin II receptor antagonist (ARB) licensed for heart failure (especially if the patient has mild to moderate heart failure [NYHA class II–III]) or
  • hydralazine in combination with nitrate (especially if the patient is of African or Caribbean origin (not including mixed race)and has moderate to severe heart failure [NYHA class III–IV])

 

Aldosterone antagonists (second-line treatment)

Formulary recommended aldosterone antagonist for heart failure;

  •  SPIRONOLACTONE initially 25mg each morning, reducing to 12.5mg daily or 25mg on alternate days if necessary

Monitoring: serum potassium, creatinine, & eGFR required at baseline, week 2, week 4, and monthly thereafter

Although the doses of spironolactone recommended for use in heart failure are much lower than those used for ascites, there is still a significant risk of electrolyte disturbance.

Patients who have had an acute MI and who have symptoms and/or signs of heart failure and LVSD, should be prescribed an aldosterone antagonist licensed for post-MI treatment. This should be initiated within 3–14 days of the MI, preferably after ACE inhibitor therapy.

Formulary recommended aldosterone antagonist for signs or symptoms of heart failure post-MI;

  • EPLERENONE initially 25mg ONCE DAILY, increased within 4 weeks to 50mg ONCE DAILY

Monitoring: serum potassium, creatinine, & eGFR required at baseline, week 2, week 4, and monthly thereafter

 

Angiotensin Receptor Blockers (ARBs) (second-line or alternative first-line treatment)

The weight of evidence supporting use of ARBs in heart failure is not as robust as it is for use of ACE inhibitors and therefore an ARB can only be recommended for those patients who are intolerant of ACE inhibitor therapy due to intractable cough.

On the basis of the currently available evidence, candesartan and losartan are the only ARBs licensed for use in heart failure.

The combination of an ACE-inhibitor, a potassium-sparing diuretic (e.g. spironolactone), and an ARB is not recommended and should be considered only after careful consideration of the potential benefits and risks.

Formulary recommended ARB;

  • LOSARTAN initially 12.5mg ONCE DAILY, increased at 1 – 2 weekly intervals, to 50mg ONCE DAILY
  • CANDESARTAN initially 4mg ONCE DAILY, doubling the dose at intervals of no less than 2 weeks, to 32mg ONCE DAILY

Monitoring: serum potassium, creatinine, & eGFR required at baseline, week 2, week 4, and monthly thereafter

The triple combination of Valsartan, ACE inhibitor and beta-blocker should be avoided, based on current evidence.

As with ACE inhibitors, it is recommended to exert particular care when using ARBs in the patient groups who are at greater risk of complications and consideration given to specialist input where appropriate.

 

Hydralazine in combination with a nitrate (alternative first-line treatment)

Hydralazine in combination with nitrate can be considered for patients with heart failure due to LVSD who are intolerant of ACE inhibitors and ARBs. Seek specialist advice.

 

Third-line treatment

Digoxin is appropriate for patients with atrial fibrillation and any degree of heart failure. It is also recommended for those with worsening or severe heart-failure due to LVSD who remain symptomatic despite treatment with an ACE Inhibitor and a beta blocker.

Digoxin may improve symptoms, exercise tolerance and reduce hospitalisations. Digoxin has not been shown to reduce mortality. Hypokalaemia predisposes to digoxin toxicity so careful monitoring of U&Es is required, especially where patients are also prescribed loop or thiazide diuretics, particularly if an ACE inhibitor, ARB or spironolactone is not co-prescribed.

Formulary recommendation;

  • DIGOXIN 62.5mcg – 125mcg ONCE DAILY (higher doses are rarely appropriate in heart failure not associated with AF)

Monitoring: serum urea & electrolytes, particularly potassium, creatinine, & eGFR required


Diuretics

A diuretic is usually required by most patients with heart failure to reduce symptoms of fluid overload, reduce hospitalisation due to acute exacerbation and increase exercise tolerance. The dose should be titrated (up and down) according to need following the initiation of subsequent heart failure therapies.

Formulary recommended loop diuretic;

  • FUROSEMIDE 20mg – 40mg ONCE DAILY (in the morning), titrated according to symptomatic response

Monitoring: serum urea & electrolytes, creatinine, & eGFR required

A thiazide diuretic may be of benefit in patients with mild heart failure and good renal function; however thiazides are ineffective in patients with poor renal function.

Formulary recommended thiazide diuretic;

BENDROFLUMETHIAZIDE 2.5mg ONCE DAILY (in the morning)

Monitoring: serum urea & electrolytes, creatinine, & eGFR required

If diuresis with one diuretic is insufficient, a combination of loop diuretic and thiazide may be tried.

Metolazone may still be recommended but has been discontinued in the UK. AMBER in Traffic Light Guidance (TLG).

Indapamide combined with furosemide has been found to be effective in a small trial of patients with massive oedema although this is an unlicensed use. (M. Tanaka et al. (2005) The Na+-excreting efficacy of indapamide in combination with furosemide in massive edema. Clinical and Experimental Nephrology, 9: 122-126)

 

Calcium channel blockers

No Calcium channel blocker is licensed for the treatment of heart failure.

The use of calcium channel blockers with a direct effect on cardiac contractility i.e. verapamil or diltiazem should be specifically avoided in heart failure.

For those patients who develop heart failure or are at high risk of heart failure NICE CG127 (Aug-11) recommends they should be changed to a thiazide-like diuretic in place of a CCB.

Where continuation of a dihydropyridine calcium channel blocker is considered essential for control of hypertension or angina, this may be justified where use of other therapies such as beta-blocker, ACE-inhibitor and diuretic has been optimised.

Ivabradine

Initiation only for patients on maximum therapy & with heart rate > 75 beats per minute

NICE TA267 Ivabradine for Treating Chronic heart failure – recommends ivabradine as a possible treatment for people with chronic heart failure provided the following conditions are all met.

  • New York Heart Association (NYHA) class II to IV stable chronic heart failure with systolic dysfunction
  • who are in sinus rhythm with a heart rate of 75 beats per minute or more
  • who are given ivabradine in combination with standard therapy including beta-blocker therapy, angiotensin-converting enzyme (ACE) inhibitors and aldosterone antagonists, or when beta-blocker therapy is contraindicated or not tolerated (after 4 week period of stabilisation on these meds)
  • with a left ventricular ejection fraction of 35% or less

Initiation may be by GP with special interest (GPwSI) or heart failure specialist nurse.

MHRA warnings on ivabradine: https://www.medicines.org.uk/emc/medicine/17188

When using ivabradine to treat the symptoms of chronic angina:

  • only start ivabradine if the resting heart rate is at least 70 beats per minute
  • do not prescribe ivabradine with other medicines that cause bradycardia, such as verapamil, diltiazem, or strong CYP3A4 inhibitors
  • monitor patients regularly for atrial fibrillation. If atrial fibrillation occurs, carefully reconsider whether the benefits of continuing ivabradine treatment outweigh the risks
  • consider stopping ivabradine if there is no or only limited symptom improvement after 3 months.

We also remind you of the following:

  •  ivabradine is indicated to treat symptoms of chronic angina in patients unable to tolerate or with a contraindication to beta-blockers – it can also be used in combination with beta-blockers in patients for whom an optimal beta-blocker dose is not enough 
  • the recommended starting dose is 5 mg twice daily
  • do not exceed the maximum maintenance dose of 7.5 mg twice daily

 

Sacubitril Valsartan (Entresto)

Draft NICE guidance published Dec 15 provisionally recommended Sacubitril Valsartan for treating chronic heart failure with reduced ejection fractioni in people with New York Heart Association class II to III symptomsii who are on a stable dose of ACE inhibitors (or angiotensin II receptor blockers for people who are intolerant of ACE inhibitors) and who have a left ventricular ejection fraction of 35% or less. Approved for use in Somerset after specialist initiation (PAMM Jan 16).

 

Algrothium

 

Prescribing guideline post myocardial infarction –Drug therapy CG 172 secondary Prevention of MI

  • Offer all people who have had an acute MI treatment with the following drugs:
    • ACE (angiotensin-converting enzyme) inhibitor
    • dual antiplatelet therapy (aspirin plus a second antiplatelet agent)
    • beta-blocker
    • statin.
  • Offer an assessment of left ventricular function to all people who have had an MI.
  • Titrate the ACE inhibitor dose upwards at short intervals (for example, every 12–24 hours) before the person leaves hospital until the maximum tolerated or target dose is reached. If it is not possible to complete the titration during this time, it should be completed within 4–6 weeks of hospital discharge.
  • Communicate plans for titrating beta-blockers up to the maximum tolerated or target dose – for example, in the discharge summary.

Offer an ACEI and aspirin to patients who have had an MI >12 months ago and also a β blocker to patients with LVSD whether symptomatic or not (new for 2013) ACE intolerant should be offered an ARB. Statins are recommended for all patients with established cardiovascular disease.

NICE does not specify preferred ACE and β blockers

Medicines with licence post MI

Ace creatnine clearance