Heart failure (HF) is an important cardiovascular disease because of the increasing prevalence, high morbidity and mortality, and rapid expansion of health care costs. Over the past decades, efforts have been made to modify the prognosis of patients with HF. Regarding HF with reduced ejection fraction (HFrEF), several drugs have shown to improve mortality and morbidity, based on large-scale randomized controlled trials, leading to a critical paradigm shift in its pharmacological treatment. The paradigm of HFrEF pathophysiology has shifted from cardiorenal disease to hemodynamic changes, and neurohormonal activation is currently considered the prime pathophysiological mechanism of HFrEF. This review summarizes evidence on the pharmacological management of HFrEF derived from major randomized controlled trials, which have accomplished improvements in survival benefits.
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