The Heart Failure Knights

by Selleckchem | Oct 08 2023

The 2021 European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure (HF) have abandoned the sequential approach for optimal drug therapy and proposed four drug classes, the so-called 4 "pillars" (angiotensin-converting enzyme inhibitors; angiotensin receptor-neprilysin inhibitors; beta-blockers; mineralocorticoid receptor antagonists and sodium-glucose co-transporter 2 inhibitors) to be initiated and titrated in all patients with reduced ejection fraction HF (HFrEF). In addition, new molecules have been considered, derived from recently reported advances from trials in HFrEF. In this review, Authors examine in particular these new molecules, as further "knights" for HF. In particular, vericiguat, a novel oral soluble guanylate cyclase stimulator, has proved effective in patients with HFrEF who had recently been hospitalized or had received intravenous diuretic therapy. The selective cardiac myosin activator omecamtiv mecarbil and the cardiac myosin inhibitors aficamten and mavacamten are under investigation. Cardiac myosin stimulator, omecamtiv mecarbil, has shown efficacy in HFrEF, lowering HF related events or cardiovascular death, while the 2 inhibitors, mavacamten and aficamten have been shown to reduce hypercontractility and left ventricular outflow obstruction improving functional capacity in randomized trials targeting hypertrophic cardiomyopathy. These agents are the prototypes of active pipelines promising to deliver an array of molecules against HF in the near future.

Comments:

It seems you're discussing the advancements in the field of heart failure (HF) treatment, particularly focusing on the new molecules that have emerged from recent trials. The 2021 European Society of Cardiology guidelines have introduced a shift from a sequential approach to a four-pillar approach for optimal drug therapy in patients with reduced ejection fraction HF (HFrEF). These four pillars include angiotensin-converting enzyme inhibitors, angiotensin receptor-neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter 2 inhibitors.

In addition to these established drug classes, new molecules have shown promise in the treatment of HFrEF. One such molecule is vericiguat, an oral soluble guanylate cyclase stimulator. Vericiguat has demonstrated effectiveness in patients with HFrEF who were recently hospitalized or received intravenous diuretic therapy.

Other molecules currently under investigation are selective cardiac myosin activator omecamtiv mecarbil and cardiac myosin inhibitors aficamten and mavacamten. Omecamtiv mecarbil, as a cardiac myosin stimulator, has shown efficacy in reducing HF-related events and cardiovascular death in patients with HFrEF. On the other hand, mavacamten and aficamten, as cardiac myosin inhibitors, have demonstrated the ability to reduce hypercontractility and left ventricular outflow obstruction, thus improving functional capacity. These trials focused on patients with hypertrophic cardiomyopathy.

Overall, these new molecules represent the ongoing progress in HF treatment. They serve as prototypes for the active pipelines of future drug development against HF. Further research and clinical trials are necessary to validate their efficacy and safety profiles and to establish their place in the management of heart failure.