Drug Therapy

Table 1. Heart failure with reduced ejection fraction is managed by using one drug from each of the classes of medications: ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), angiotensin receptor blocker plus neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonist (MRAs), beta blocker (BBs), and vasodilators.

Key Points

  • Drug therapy is the key intervention in chronic heart failure (CHF) in patients with reduced ejection fraction
  • Many patients are frequently hospitalized or die prematurely because clinicians do not use an adequate dosage of evidence proven medications
  • Using recommended CHF medications at target doses has a potential benefit of 50-60% reduction in mortality over 1 to 3 years
  • Replacement of ACE inhibitor or ARB with Entresto yields further significant symptomatic and mortality benefits
  • If heart rate remains elevated above 70 bpm despite target dose of a beta blocker,  ivabradine can be added to further decrease heart rate and result in significant further decrease in the combined endpoint of cardiovascular death and heart failure hospitalization
  • Achieving target dosages of medications requires a strategy and the STEPPED CARE approach illustrated below is one of the most effective methods because patients buy-in to the approach upfront and expect the dosage increases and are more likely to adhere to the new regimen 

Using the STEPPED CARE Approach

  • STEPPED CARE is the most effective way of achieving target dosages of evidence based medications for patients with reduced ejection fraction.
  • STEPPED CARE satisfies the shared decision making domain of high quality care delivery. 
  • STEPPED CARE begins  by  starting one medication from each CHF Drug Class at a low dose (the initial dosage).
  • The next step is to sequentially increase the dosage of each medication one at a time until each drug is at the target dosage used in clinical trials (target dosage).
  • It is important to start one drug from each class before beginning the STEPPED CARE titration process.  This is because most clinical trials test a new drug by using it on top of other drugs previously  shown to be effective and in order to get the benefits shown in the trial we should use it exactly the same way as it was studied. 
  • STEPPED CARE example: A 55 year old male patient with an EF of 35% was first started on the initial dose of a beta blocker: bisoprolol, an ARNI: Entresto, and a MRA: spironolactone. In a subsequent clinic visit the beta blocker was increased to the step one dosage (below). A few weeks later the spironolactone was increased to its step one dosage. The Entresto initial and step one dose are the same so it can be left alone while the other medications are brought up to their respective step one doses. If the patient remains stable on step one dosage of all three medications then the Entresto can be raised to its step two dose. If patient tolerates this change for a few weeks and labs remain acceptable then the beta blocker can be moved to its  step 2 dose followed by the the spironolactone step 2 dose a few weeks later. When all three are at step two doses, the Entresto is raised to the step three dose followed in sequence by the other two drugs.  
  •  As you can see, from the above example, the patient even at step two doses of the three drugs is already on a reasonable evidence based regimen and if he becomes clinically borderline from a blood pressure standpoint, there is no harm in waiting at step two doses until hemodynamic stability is assured.  
  • The STEPPED CARE method works well because the patient already knows that the goal is to achieve the highest step of each medications. In fact, the patient can be given the print out of the STEPPED CARE chart so they know which drug will be raised next.. 


  • Initial dose: 2.5 mg PO QD
  • Step one: 5.0 mg PO QD
  • Step two: 7.5 mg PO QD
  • Step three: 10 mg PO QD

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Notes: Increase dose to next step every 2 weeks


  • Initial dose: 24/26 mg PO BID
  • Step one: 24/26 mg PO BID
  • Step two: 49/51 mg PO BID
  • Step three: 97/103 mg PO BID

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Notes: Increase dose to next step every 2 weeks


  • Initial dose: 12.5 mg PO QD
  • Step one: 12.5 mg PO BID
  • Step two: 25 mg PO QD
  • Step three: 50 mg PO QD

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Notes: Check potassium within 7 days and then periodically