New Therapies for Heart Failure Could Save Thousands of Lives

“Common, costly, and deadly,” were the key characteristics used to describe the scope of heart failure (HF) as a health issue at PriMed West.

On the estimate of the 6 to 12 million resultant outpatient visits per year from these cases, Gregg C. Fonarow, MD, Director of the Ahmanson-UCLA Cardiomyopathy Center and Co-Chief of the UCLA Division of Cardiology, said that primary care physicians (PCPs) are indispensable in evaluating and managing HF in these patients. “There are close to 5.7 million men and women with HF, there may be close to a million new cases of HF this year, mortality rates remain high, close to 50% at 5 years, and over a million patients will be hospitalized with HF as the primary diagnosis.”

Fonarow and Tamara Horwich, MD, Medical Director of the UCLA Cardiac Rehabilitation Program, and Co-Director of the UCLA Women's Cardiovascular Health Center, led the discussion on new treatment options and recommendations for PCPs in the care of their diabetic patients with HF. “It is really important for PCPs to be aware of the full contingent of therapies to reduce this very high burden of morbidity and mortality.”

According to Fonarow, many patients are still not on one or more of the guideline-recommended, mortality-reducing therapies. “Patients are having hospitalizations and deaths that could have been prevented with better implementation of our evidence-based therapies.”

Fonarow cited progress in the understanding of vasoconstricting neurohormonal systems such as the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS) as the foundation upon which major therapeutic advances have been made over the last few years using neurohormonal antagonists. He said that researchers have also understood that there is a beneficial, counter-regulatory neurohormonal system — the natriuretic peptide system (NPS) – that can counteract the effects of RAAS and SNS.

In addition to NPS, other endogenous vasoactive peptides (adrenomedullin, bradykinin, substance P, calcitonin gene-related peptide) can also decrease neurohormonal activation, but these molecules are degraded by neprilysin, creating a therapeutic option in HF by use of neprilysin inhibitors. Horwich described the mechanism of action of one of these therapies, sacubitril/valsartan, also known as angiotensin receptor-neprilysin inhibitor (ARNI), an angiotensin receptor blocker/neprilysin inhibitor.

Horwich detailed results from the signature trial (PARADIGM) that compared ARNI with enalapril, an angiotensin-converting enzyme (ACE) inhibitor. “ARNI led to a statistically significant reduction of 20% in both cardiovascular (CV) death and hospitalization for HF compared with the ACE inhibitor. A very positive trial.” Horwich also noted that fewer adverse events occurred with ARNI.

Before introducing the audience to another new therapy for HF patients, Horwich first reviewed a meta-analysis of 17 randomized trials in patients with HF who were given beta-blockers. The goal was to assess whether the beta-blocker dose or the amount of heart rate reduction could explain differences seen in patient outcomes among HF beta-blocker trials, 1966 to 2008. “After adjusting for multiple factors, there was a significantly decreased risk associated with lowering the heart rate and not associated with the beta-blocker dose, telling us that heart rate reduction in HF is a valuable endpoint to examine.”

Horwich reminded the audience that the sinus node is responsible for regulating heart rate, and reviewed the currents involved in this regulation, focusing specifically on the so-called “funny current” (I_f) that controls the rate of spontaneous activity of sinoatrial node myocytes.

A new drug, ivabradine, is a specific inhibitor of the I_f current that prolongs diastolic duration to slow heart rate, but has no action on other cardiac channels and does not affect cardiac contractility. The SHIFT study demonstrated the efficacy of ivabradine, with a statistically significant 18% reduction in CV death or hospitalization for worsening HF.

In concluding her remarks with a discussion of estimates of the target population for the new HF therapies, Horwich said, “If we implement these new HF therapies such as ARNI and ivabradine in patients who are eligible per the new guidelines but who are not getting these treatments, we can save many lives per year, perhaps as many as 68,000, based on these estimates.”