The European Society of Cardiology recently announced the new guidelines for the treatment of heart failure with reduced ejection fraction (HFrEF) using four drug classes.

However, local health experts said the guidelines might be “insufficient” to apply to Korean patients.

Korean heart failure specialists discussed issues the ESC’s revised guidelines would create if applied to domestic patient care at the Korean Society of Cardiology (KSC 2021) on Sunday.

The ESC guidelines recommended early and simultaneous treatment based on four drug classes, ACEi/ARNI, BB, MRA, and SGLT-2i, recommended with the highest grade in HFrEF patients.

With each drug class’s mortality reduction effect combined, the four-drug combination treatment can reduce the death rate of one in four HFrEF patients, the guidelines said.

Also, the ESC guidelines took out ARB, which had been recommended in the same level as ACEi, from the priority list. Instead, the guidelines added Forxiga (dapagliflozin) and Jardiance (empagliflozin) as the top-recommended drugs among SGLT-2i drugs.

Professor Cho Jae-yeong of cardiovascular medicine at Chonnam National University Hospital had a presentation, “What’s New Changes in HFrEF,” at the KSC 2021.

Cho said SGLT-2 inhibitors have excelled in heart failure treatment recently.

Landmark clinical trials, such as DAPA-HF and Emperor-Reduced studies, have contributed to obtaining the highest recommendation rating for SGLT-2i drugs for the treatment of HFrEF, he said.

In particular, dapagliflozin proved the effect of lowering death risk, he said.

The ESC also picked ARNI, or Entresto (sacubitril/valsartan), as the top-recommended drug in HFrEF, based on trials including the PARAGON-HF study, Cho went on to say.

“Also, the PROVE-HF study even showed that an early use of ARNI has a ‘heart remodeling effect’ such as increased ejection fraction and decreased volume,” he added.

Based on these pieces of evidence, the ESC revised its guidelines for the first time in five years to recommend “early” and “simultaneous” use of the four drug classes -- ACEi/ARNI, BB, MRA, and SGLT-2i – for HFrEF treatment, Cho said.

However, in a panelists’ discussion, many cardiologists pointed out several issues regarding the new ESC guidelines.

Professor Yoo Byung-su of cardiology at Wonju Severance Christian Hospital said Forxiga and Jandiance became the top-recommended drugs and included SGLT-2 inhibitors in the four-drug classes were based on “relatively generous evaluations compared to other agents.”

Yoo said heart failure treatment could be evaluated as a reduction in mortality and hospitalization.

Dapagliflozin among SGLT-2 inhibitors proved such an effect, but empagliflozin failed to prove a benefit in death reduction, he noted.

“The ESC gave the grade 1 rating to these drugs based on the meta-analysis of studies of the two drugs which showed the effect of mortality reduction,” he said.

In real clinical care, physicians prefer medicines that are easier to use and have fewer side effects than those difficult to set the dose and manage side effects, Yoo said.

“The key HFrEF treatment, suggested by the latest guidelines, is to use the four drugs at the same time. But this could yield a completely unexpected outcome in real clinical care,” he said.