Heart Failure Therapy: The Good, the Bad, and the Ugly

AUGUST 02, 2016
The central problem in heart failure is not that patients are short of breath or retain fluid. The problem is that they die. –Dr. Arnold Katz1
Those words resonate in our current era of outcomes-focused heath care perhaps even more than when they were penned in 1993.
In the 1980s, the primary pharmacologic agents for heart failure with reduced ejection fraction (HFrEF) were digoxin and hydralazine-isosorbide dinitrate (H-ISDN). The field has come a long way since then, with the emergence of cornerstone therapies like beta-blockers and mineralocorticoid receptor antagonists (MRAs). 

I previously summarized the recent guideline recommendations for 2 new HF therapies: the angiotensin receptor blocker-neprilysin inhibitor (ARNI) combination of sacubitril/valsartan (Entresto), and the funny current inhibitor ivabradine (Corlanor). Several recent post-hoc analyses further clarify the role of these new agents.

The Good
  • The reduction in HF-related hospitalization was seen within 30 days of randomization to ARNI over enalapril.2 Patients randomized to ARNI also had fewer emergency department visits and were less likely to require outpatient intensification of medical therapy.
  • Rates of hospital readmission for HF at 30 days were also lower in patients assigned to ARNI therapy versus enalapril.3
  • Among cardiovascular (CV) deaths, both sudden cardiac death and death due to worsening HF were reduced by treatment with ARNI versus enalapril.4 Of note, the reductions in rates of sudden death weren’t influenced by the presence of an implantable cardioverter defibrillator (ICD), which is noteworthy because the PARADIGM trial has been criticized for low use of ICD therapy. 
  • The magnitude of benefit for patients on lower doses of ARNI therapy relative to those on lower doses of enalapril was similar to that of patients who remained on target doses of both drugs.5 In other words, even patients only able to tolerate lower doses of an angiotensin-converting enzyme inhibitor (ACEI) may still benefit from switching to a lower dose of ARNI therapy.
  • ARNI therapy is more expensive than enalapril when only considering direct costs. However, 2 recent papers reported acceptable cost effectiveness of ARNI therapy over enalapril (approximately $50,000/QALY).6,7
One important caveat is this entire data set is from a single large clinical trial where patients of African descent and those with severe HF weren’t well represented. However, the potential benefits of ARNI are hard to ignore. Of 2,736,000 HFrEF patients in the United States, 2,287,296 (84%) are projected to be candidates for ARNI therapy.8 Optimal implementation of ARNI therapy is empirically estimated to prevent 28,484 deaths per year in the United States alone.8

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.