New Heart Failure Guidelines: What Pharmacists Need to Know

MAY 22, 2016
It was a busy weekend in the world of heart failure (HF), as both the American College of Cardiology/American Heart Association (ACC/AHA) and the European Society of Cardiology (ESC) published updated guidelines on May 20, 2016.
The ACC/AHA guidelines is a focused update on 2 new drug therapies for patients with HF and a reduced ejection fraction,1 while the ESC guideline is a much more comprehensive overview of the management of both acute and chronic HF.2

1. Entresto Receives Class I Recommendation Over ACE Inhibitors and ARBs1,2
The combination of sacubitril/valsartan (Entresto), an angiotensin-receptor/neprilysin inhibitor
(ARNI), has demonstrated superior reductions in both mortality and HF-related hospitalization compared with the angiotensin-converting enzyme (ACE) inhibitor enalapril. These data are quite striking, as ACE inhibitors have been the cornerstone of drug therapy for HF for over 2 decades. 
In light of these positive data, the ACC/AHA guidelines recommend the use of Entresto in patients with chronic symptomatic HF with a reduced ejection fraction (NYHA class II or III) who tolerate an ACE inhibitor or an angiotensin receptor blocker (ARB) in order to further reduce morbidity and mortality (Class I, level of evidence B).

The ESC guidelines provide a softer endorsement for ARNI therapy, recommending it should only be used in patients who remain symptomatic despite optimal treatment with either an ACE inhibitor or ARB in combination with a beta-blocker and a mineralocorticoid receptor antagonist (eg, spironolactone) (Class I, level of evidence B). 

While the mortality and morbidity reductions with ANRI therapy are impressive, the drug does have potential limitations:
  • Rates of symptomatic hypotension are higher than with ACE inhibitor monotherapy. Patients need close blood pressure monitoring when starting or titrating ARNI therapy. 
  • The number of patients of African descent was very small in the pivotal clinical trial. Therefore, the benefits in this group of patients are not known.
  • Long-term safety data are lacking, and there are theoretical toxicities associated with long-term inhibition of neprilysin. For instance, neprilysin affects the degradation of beta-amyloid peptide in the brain, which could theoretically accelerate amyloid deposition (eg, Alzheimer's disease). However, a recent, small, 14-day study with healthy subjects showed elevation of the beta-amyloid protein in the soluble rather than the aggregable form, which, if confirmed over longer time periods in patients with HF, may indicate the cerebral safety of Entresto.
  • Entresto cannot be combined with an ACE inhibitor, and a 36-hour washout period is required between these 2 therapies to minimize the potential for life-threatening angioedema. This represents a huge opportunity for pharmacists to intervene and help prevent a potentially catastrophic medication error. 
  • All patients in the clinical trials were able to tolerate high doses of ACE inhibitor therapy so caution and close monitoring is needed when starting Entresto in patients who have not previously been on either an ACE inhibitor or an ARB.
  • Patients with severe HF (eg, NYHA class 4) were not well-represented in the clinical trial with Entresto, so its use in these patients cannot be endorsed at this time. 
  • The cost of this medication is significantly higher than generic ACE inhibitor therapy. Therefore, pharmacists should make sure that patients who are prescribed this therapy are able to afford the medication. Novartis offers several patient assistance programs that can be accessed through its website. 
Even with these limitations in mind, I believe Entresto represents the future of HF drug therapy. I would personally recommend this therapy as the preferred vasodilator therapy for patients with either class II or class III symptoms, especially in those already taking ACE inhibitor or ARB therapy. 
Pharmacists can play a key role in both identifying patients who may be good candidates for Entresto, as well as monitoring patients for hypotension and angioedema during the transition phase. Pharmacists can also help to ensure that patients never take an ACE inhibitor concomitantly with Entresto, and should always question when a patient already taking one of these therapies is prescribed the other.

Douglas Jennings, PharmD, FCCP, FAHA
Douglas Jennings, PharmD, FCCP, FAHA
Douglas Jennings, PharmD, FCCP, FAHA, FACC, currently practices as the clinical pharmacy manager in heart transplant and mechanical circulatory support at New York Presbyterian Columbia University Medical Center. He is a past chair of the American College of Clinical Pharmacy (ACCP) Cardiology PRN, and he is a fellow of ACCP, the American Heart Association, and the American College of Cardiology.