Finally, a weapon against HFpEF

Experts welcome the approval of a popular diabetes drug for patients with this type of heart failure.

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A drug currently used to treat reduced ejection fraction heart failure, empagliflozin (Jardiance, Boehringer Ingelheim/Lilly), has had its indication expanded by the TGA to include symptomatic heart failure independent of changes to the ejection fraction.

This means patients with preserved ejection fraction heart failure (HFpEF) can now access the medication, although it is not yet listed on the PBS for this indication.

“This is fantastic because we’ve had nothing, up until now, which treats heart failure with preserved ejection fraction,” said Professor Andrew Sindone, director of the heart failure unit and department of cardiac rehabilitation at Concord Hospital.

Professor Sindone, who has served on boards and committees for Eli Lilly Australia and Boehringer Ingelheim, said preserved ejection fraction heart failure has a big burden of illness. In addition to being common and killing many people, he noted that it badly impacts quality of life.

Heart failure affects about 500,000 Australians with around 60,000 new cases diagnosed per year. About half are preserved ejection fraction heart failure. One in four of those patients die within a year of being diagnosed and only a third survive beyond five years from their first episode.

Heart failure is also expensive. People hospitalised with heart failure stay an average of almost seven days and have a 29% chance of being readmitted within 30 days.

“An average day in the hospital now is about $2500, so if we can prevent some hospitalisations that will save the community a lot of money,” Professor Sindone, head of the department of cardiology at Ryde Hospital, told TMR.

“This will make patients feel better, live longer, and keep them out of hospital,” he said.

Management of the condition has so far consisted of controlling fluid retention and blood pressure, managing risk factors and comorbidities that tend to include coronary artery disease, atrial fibrillation, obesity, diabetes, renal impairment and pulmonary hypertension. The existing options can affect symptoms but not mortality.

The SGLT2 (sodium–glucose co-transporter 2) inhibitor has been shown to reduce the relative risk of cardiovascular death or hospitalisation in patients with left ventricular ejection fraction  regardless of ejection fraction.

A randomised controlled trial comparing use of empagliflozin with standard therapy and placebo with standard therapy found the former led to a 21% lower relative combined risk of cardiovascular death or hospitalisation, and 29% lower for hospitalisation, in patients with preserved ejection fraction heart failure, with or without diabetes.

The study, published in NEJM in 2021, also found that the group that took empagliflozin had a lower total number of hospitalisations for heart failure, and a longer time to first hospitalisation. The results were very similar to the use of SGLT2 inhibition in patients with reduced ejection fraction heart failure.

Another study, published in September 2022 using dapagliflozin, suggested that taking the SGLT2 inhibitor provided benefit through the full range of ejection fraction.

Use of an SGLT2 inhibitor (empagliflozin) for patients with reduced ejection fraction heart failure was recommended in the consensus statement of Australian clinicians published in August 2022 in the MJA.

The drug can now be accessed for preserved ejection heart failure through private prescription in Australia. It is already available on the PBS as a treatment for type 2 diabetes and, along with dapagliflozin (Forxiga), for heart failure with reduced ejection fraction.

“SGLT2s are not diabetic medications,” Professor Sindone quipped. “They’re heart failure medications that have a side effect of lowering glucose.”

“It’s all about losing fluid, lowering your blood pressure, lowering your heart rate, increasing ketone bodies and increasing erythropoietin for improved tissue oxygenation,” he said.

“They also reduce uric acid, which is toxic to the heart, they help reduce pericardial fat so there’s less inflammation around the heart. There are lots of benefits. They’re really very good medications for the heart.”

Side effects include passing more urine, which can be a problem sometimes, as well as an increased risk of thrush in women and balanitis in men. In addition, SGLT2s should be avoided if the patient has diarrhoea or severe respiratory illness, said Professor Sindone. And they have to be stopped for three days before anaesthetic or a procedure such as colonoscopy to reduce the risk of euglycemic ketoacidosis.

They also seem to be nephroprotective, he pointed out, with kidney function reduced at first but then bouncing back within one to three months and remaining stable. Studies show that kidney function continues to deteriorate for those on placebo.

“The medication is there now. It’s got lots of data from multiple trials and metanalyses showing benefits,” Professor Sindone told TMR.

“We now have a weapon against heart failure with preserved ejection fraction, whereas previously we had nothing.”

Editor’s note: This story has been amended to include Professor Sindone’s links to Eli Lilly Australia and Boehringer Ingelheim.