Empagliflozin reduces CV death or hospitalisation for heart failure in patients with HFpEF

By Rebecca Jenkins
The sodium–glucose cotrans­porter-­2 (SGLT­-2) inhibitor empagliflozin reduces the risk of the composite of cardiovas­cular death or hospitalisation for heart failure (HF) in patients with HF and preserved ejection fraction (HFpEF), an international double­-blind study shows.

The manufacturer­ funded EMPEROR­-Preserved Trial randomly assigned 5988 patients with New York Heart Associa­tion functional class II to IV HF and an ejection fraction (EF) of more than 40% to receive empagliflozin (10mg once daily) or placebo, in addition to usual therapy.

Over a median of 26.2 months, cardiovascular death or hospitalisation for worsening heart failure occurred in 415 of 2997 patients (13.8%) in the empagliflozin group compared with 511 of 2991 patients (17.1%) in the placebo group, a relative risk reduction of 21%.

‘This effect was mainly related to a lower risk of hospitalisation for HF in the empagliflozin group,’ the authors wrote in The New England Journal of Medicine.

The effects of the drug seemed consistent in patients with and without diabetes.

Professor Tom Marwick, Director of the Baker Heart and Diabetes Institute, Melbourne, said treating HFpEF was a ‘real headache’, as it accounted for more than half of HF cases but had no specific therapy.

HF specialists were keen to see good news about HFpEF, but Professor Marwick, who is a cardiologist with Alfred Health and Western Health, cautioned the latest trial findings risked being overplayed.

The main benefit was number of hospital admissions with HF, he noted, with no effect on total hospitalisations, no survival benefit and no improvement of HF clinical score according to a range of prespecified analyses.

‘Sorry to say this, but my patients with HFpEF want to feel better and want to stop coming to hospital. I’m not sure they really care about the admission diagnosis,’ he said.

‘I think patients with HFpEF will be treated with SGLT­-2 inhibitors, and some hospitalisations will be saved. However, in my opinion, this is being hyped more than is justified.’

Professor Marwick also noted that the best outcomes with empagliflozin were seen in the subgroup of patients with a mid­range EF of less than 50% compared with those patient groups who had higher EFs.

The definition of HFpEF had been tightened in recent years, he said, but it remained a ‘pretty unsatisfactory way’ to define an illness.

‘Generally, when that happens in medicine (e.g. "nonulcer dyspepsia") it ends up being a ragbag to stuff various entities we don’t understand or cannot measure. This is a huge barrier and it implies the lack of a specific target,’ he said.

‘In fact, there are multiple targets and until we accept that we need a trial of the myocardial relaxation variant of HFpEF or the metabolic heart disease variant, we are destined to witness more negative test results.’
N Engl J Med 2021; doi: 10.1056/NEJMoa2107038.