Medical treatment of heart failure with reduced ejection fraction: the dawn of a new era of personalized treatment?

Recent trials have shown the efficacy of new drugs for the medical therapy of heart failure and reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduced hospitalizations for HF, HF events, and cardiovascular death in patients with HFrEF or hospitalized for HF. Iron repletion with ferric carboxymaltose (FCM) improved symptoms, functional capacity, and quality of life in chronic HFrEF patients, and decreased the risk of subsequent HF hospitalizations in subjects with acutely decompensated HF. New-generation potassium binders may allow initiation and up-titration of renin-angiotensin-aldosterone system inhibitors (RASi). Lastly, the guanylate cyclase stimulator vericiguat and the myosin activator omecamtiv mecarbil reduced the primary endpoint in two major controlled trials. These results open novel pathways for the treatment of HFrEF. This review discusses new opportunities of an individualized approach to HFrEF pharmacotherapy, where new compounds expand a spectrum of drugs that target primarily neuroendocrine activation. SGLT2i can be safely applied once daily at a fixed dose to the vast majority of patients with HFrEF, including those with moderate renal dysfunction and/or systolic blood pressure as low as 95-100 mmHg. Additional medications are suitable for more specific phenotypes, with ivabradine providing benefit in patients with sinus rhythm and heart rates ≥70 beats per minute, FCM in the presence of iron deficiency, and potassium-lowering agents to implement RASi when hyperkalaemia occurs. Vericiguat and omecamtiv mecarbil also have potential for tailored approaches towards the hemodynamic status. Thus, a new era is starting for a more personalized medical treatment of HFrEF.