THE CONTEXT
The passage provides starting and target doses for several heart failure drugs and describes the benefits, initiation precautions and clinical roles of beta-blockers, ivabradine and digoxin.
ACE inhibitor and angiotensin receptor blocker doses
| Feature | Details |
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Enalapril | start at 2.5 mg twice daily; target 10 mg twice daily. |
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Lisinopril | start at 2.5 mg daily; target 20 mg daily. |
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Ramipril | start at 1.25 mg daily; target 10 mg daily. |
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Losartan | start at 25 mg daily; target 100 mg daily. |
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Candesartan | start at 4 mg daily; target 32 mg daily. |
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Valsartan | start at 40 mg daily; target 160 mg daily. |
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Beta-blocker and neprilysin inhibitor–ARB doses
| Feature | Details |
|---|
Bisoprolol | start at 1.25 mg daily; target 10 mg daily. |
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Metoprolol | start at 25 mg twice daily; target 100 mg twice daily. |
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Carvedilol | start at 3.125 mg twice daily; target 25 mg twice daily. |
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Sacubitril–valsartan | start at 24/26 mg twice daily; target 97/103 mg twice daily. |
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Beta-blocker effects and initiation
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Beta-blockade counteracts the deleterious effects of enhanced sympathetic stimulation and reduces arrhythmias and sudden death.
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Initiation at standard doses may precipitate acute-on-chronic heart failure. Small incremental doses can increase ejection fraction, improve symptoms, reduce hospitalisation and reduce mortality.
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Beta-blockers also reduce the incidence of atrial fibrillation and ventricular arrhythmia.
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A typical bisoprolol regimen increases gradually from 1.25 mg daily to 10 mg daily over 12 weeks.
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The stated relative reduction in mortality risk is 33% with beta-blockers compared with 20% with ACE inhibitors.
Ivabradine
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Ivabradine acts on the If inward current in the sinoatrial node, reducing heart rate.
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Typical doses are 2.5–5 mg twice daily, increasing to 7.5 mg twice daily if necessary.
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It reduces hospital admission and mortality in heart failure caused by moderate or severe left ventricular systolic impairment.
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Trial effects were greatest when heart rate exceeded 77/min. It is best suited to patients who cannot take beta-blockers or whose heart rate remains high despite beta-blockade.
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Ivabradine is ineffective in patients with atrial fibrillation.
Digoxin
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Maintenance digoxin at 0.0625–0.25 mg daily can provide rate control in patients with heart failure and atrial fibrillation.
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In severe heart failure, described as NYHA class III–IV, digoxin reduces hospitalisation for heart failure but does not affect long-term survival.