Researchers Still Looking for Effective Treatment for Heart Failure with Preserved Ejection Fraction

SEPTEMBER 20, 2016
W. Todd Penberthy,PhD
HFSA 2016, HFSA, heart failure, heart failure with preserved ejection fraction, HFpEF, cardiology, internal medicine, surgery, primary care, hospital medicine, ACE inhibitor, angiotensin receptor blocker, beta blocker, mineralocorticoid receptor antagonist, spironolactone, geriatrics, hypertension, diabetes, renal dysfunction, sleep apnea, anemia, endocrinology, pulmonology, critical care, emergency medicine, nitric oxide, vericiguatNo treatment has been shown to convincingly reduce mortality in patients with heart failure (HF) with preserved ejection fraction (HFpEF). Clinical trials investigating treatments for this population have been consistently disappointing to date. ACE inhibitors, angiotensin receptor blockers, beta blockers, and mineralocorticoid receptor antagonists have all failed to significantly reduce mortality in HFpEF patients.
At the 2016 annual meeting of the Heart Failure Society of America, Orly Vardeny, PharmD, MS, associate professor at the University of Wisconsin School of Pharmacy and Medicine and a clinical pharmacy specialist at the William S. Middleton Memorial VA Hospital, in Madison, WI, reviewed recent clinical trial data focused on HFpEF.
The TOPCAT spironolactone trial did not meet primary outcome goals, but did result in reduced hospitalizations as compared to placebo. The dramatic regional variation reported between US, Canada, Argentina, and Brazil multicenter trials as compared to Russia and Georgia trials turned out to be due to misrepresentation of compliance, as the expected metabolites were not detected in many of the Russian and Georgian patients. Thus, the Russian and Georgian data is largely ignorable.
Vardeny emphasized that HFpEF is an extremely comorbid condition that usually includes older patients who are more likely to have hypertension (most common), diabetes, renal dysfunction, sleep apnea, and anemia. Accordingly, it is just as important to treat the comorbidities. Beta blocker use, however, has fallen out of favor.
In summary, when it comes to current treatments for HFpEF, Vardeny said physicians have to be extra cautious with diabetes patients, and manage comorbidities with aggressive control of hypertension, diabetes, and ischemic heart disease. Treatment with spironolactone did reduce hospitalizations, and so clinicians may want to use it more frequently for treating HFpEF patients.
Novel burgeoning treatment targets for HFpEF include focusing on nitric oxide (NO) signaling, which is impaired in HFpEF. One strategy is to increase production of NO, according to Vardeny. The NO-dependent cGMP pathway can be targeted by multiple approaches including: (1) PDE5 inhibitors like sildenafil (RELAX trail), (2) sGC activators/inhibitors (LEPHT trial), (3) nitrates (NEAT-HF), or (4) neprilysin inhibitors (PARAMOUNT trial).

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