Both European and American guidelines now recommend the first in class angiotensin receptor-neprilysin inhibitor (ARNI) valsartan with sacubitril (Entresto) over ACE inhibitors in heart failure patients with reduced ejection fraction (HFrEF).
Currently available in Australia under compassionate access, Entresto demonstrated an impressive effect size in the PARADIGM-HF study – reducing hospitalisations, cardiovascular and overall mortality compared to ACE inhibitors.
However in March this year the PBAC did not recommend its listing on the PBS “on the basis of uncertain cost-effectiveness and high predicted financial impact”.
Professor Thomas Marwick, director of the Baker IDI Heart & Diabetes Institute, said both guidelines also highlight the potential risks associated with ARNI use such as hypotension and angioedema.
“The run-in phase of the PARADIGM-HF trial can underestimate the magnitude of any side effects. However clinical experience suggests the side effects are not problematic,” he told the limbic.
Professor Marwick said the American guidelines now also include ivabradine, a sinoatrial node modulator effective in reducing heart rate in HFrEF patients, which has been in the European guidelines since 2012.
“Ivabradine is available in Australia but probably has not had the footprint you might expect. It’s possible we’re more aggressive with beta-blockers or we feel we achieve adequate heart rate control,” he said.
Professor Marwick added that the American update was out of sync with European guidelines by not including GLP inhibitor empagliflozin to prevent or delay heart failure in patients with type 2 diabetes.
“Heart failure is probably the most common complication of diabetes and empagliflozin is one of a group of agents historically evaluated for glucose control but not for cardiovascular outcomes.”
“In the EMPA-REG OUTCOME study the survival curves diverge almost immediately which suggests the mechanism of action is not related to stabilising plaque as you would expect that to take time.”
He said an effect on blood pressure was another potential explanation for the benefit as even a 2mm Hg reduction could lead to a survival benefit over 5-10 years.