What constitutes optimal neurohumoral antagonism in chronic heart failure?

Dual angiotensin and neprilysin inhibition using the combination drug sacubitril-valsartan has ushered in a new era in the treatment of heart failure (HF). The randomized controlled PARADIGM-HF trial, which randomized 8399 patients with HF to enalapril or sacubitril-valsartan, showed a 20% reduction in mortality and HF hospitalization with the new drug. This has been heralded as a step toward filling a crucial gap in HF management by providing strong evidence that combined inhibition of the angiotensin receptor and neprilysin is superior to inhibition of the renin-angiotensin system alone in stable patients with chronic HF as it negates the deleterious effects of angiotensin while concomitantly augmenting the beneficial effects of the endogenous natriuretic peptide system. This new therapy is costly, and other confirmatory studies have been lacking for over 2 years since its approval by major regulatory authorities. As such, controversy and heated discussions have amassed, as has detailed information from a plethora of secondary analyses of this pivotal trial about the pros and cons of this promising new therapeutic strategy in HF management. The aim of this review was to provide a critical assessment of all these aspects.

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Neurohormones and death in systolic heart failure: keep your friends close, but your enemies closer

Borovac

2021

Heart

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What constitutes optimal neurohumoral antagonism in chronic heart failure?

Cited by 3 publications

References 71 publications

The Patient with Advanced Chronic Heart Failure

The Patient with Advanced Chronic Heart Failure

Neprilysin Inhibitors: Filling a Gap in Heart Failure Management, Albeit Amidst Controversy and at a Significant Cost

Neurohormones and death in systolic heart failure: keep your friends close, but your enemies closer

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