Heart failure

3 novel therapies for heart failure – Prof John Teerlink


Prof. John Teerlink

With SGLT2 inhibitors now joining the mainstream of therapies for heart failure, it’s time to look at other novel approaches such as intravenous iron, vericiguat and omecamtiv mercarbil, according to an international expert.

Speaking at CSANZ 2020 virtual meeting, Professor John Teerlink of the University of California, San Francisco, said much could still be achieved in heart failure by ensuring patients are receiving  appropriate doses of the cornerstones of treatment: angiotensin agents, beta blockers, aldosterone receptor antagonists – and most recently, the SGLT2 inhibitors.

“It’s now becoming clear that these diabetic drugs that would help heart failure are now becoming heart failure drugs that will help diabetes,” he said.

But looking beyond these “four pillars” of pharmacotherapy, there are also gains to be made by identifying and treating the 15-30% of heart failure patients with iron deficiency, according to Professor Teerlink.

Iron deficiency is an independent risk factor in chronic heart failure patients and there is now good evidence that ferric carboxymaltose can improve patient reported outcomes and functional status. The AFFIRM-AHF trial published in The Lancet in 2020 also showed that iron therapy in patients with acute HF reduced rehospitalisations, he noted.

“The irony is that iron deficiency is easier and cheaper to test than most of the things we investigate in our heart failure patients,” he said.

There was also emerging evidence to support the use of the soluble guanylate cyclase (sGC) stimulator, vericiguat, Professor Teerlink told the meeting.

By stimulating the production of cGMP, vericiguat addresses the cGMP deficiency to improves myocardial dysfunction in the same way as sacubitril/valsartan, he explained.

In the VICTORIA study, published in the NEJM in 2020, patients with HfrEF (NYHA Class II-IV) treated with vericiguat showed a  10% reduction in the primary outcome of HF hospitalisation and cardiac death compared to a placebo group.

And importantly, the adverse effect of hypotension seen with other drugs in the sGC class did not appear to be a significant problem in the VICTORIA trial of vericiguat, he said.

The other novel therapies for HF worth are the cardiac myosin activators, that improve cardiac performance by acting as myotropes to improve molecular and ‘scaffolding’ functions of the heart.

Professor Teerlink explained that omecamtiv mercarbil acted to stabilise actin in the pre-powerstroke state, increasing the entry rate of myosin into the tightly-bound, force-producing state with actin. The analogy is having more hands (myosin heads) to grasp the rope (actin filament) to produce more force.

Professor Teerlink was the lead investigator in the GALACTIC-HF NEJM trial involving more than 8250 patients with HF, which showed that omecamtiv mercarbil was associated with an 8% reduction in first HF event.

Interestingly we also saw suggestion of improvement in the symptom score in patients enrolled as inpatients although overall there was no significant difference,” he said.

The benefits were seen across all patient subgroups although omecamtiv mercarbil appeared to provide more benefit for those with more advanced or worse HF, he noted.

It showed no adverse effect on BP, renal function or potassium homeostasis, though there were reductions in heart rate and NT pro-BNP. NO adverse effects were seen in relation to MI or arrythmia.

Disclosure statement: Professor Teerlink declared consulting fees and/or research funding from pharmaceutical companies including Amgen, Cytokinetics (omecamtiv mercarbil), Bayer and Merck (vericiguat).

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