Heart failure is a common entity encountered in healthcare with a vast 
socioeconomic impact. Recent advances in pharmacotherapy have led to the 
development of novel therapies with mortality benefits, improvement in heart 
failure symptoms and hospitalizations. This article is intended to explore those 
newer pharmacotherapies and summarize the evidence behind guideline directed 
medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF). 
It has been several years since any significant advances in pharmacotherapy of 
heart failure have resulted in survival benefit. Angiotensin-neprilysin 
inhibitors through the PARADIGM-HF and PIONEER-HF trials have shown mortality 
benefits and a reduction in heart failure hospitalizations and are considered 
landmark trials in heart failure. Vericiguat is an oral guanylate cyclase 
stimulator that through the recent VICTORIA trial showed a 10% relative 
difference in death from cardiovascular cause or hospitalization for heart 
failure. The sodium-glucose transport protein 2 (SGLT2) inhibitors are another 
class of medications that have shown promise in the treatment of patients with 
HFrEF and diabetes mellitus. The CANVAS and EMPA-REG OUTCOME trials showed the 
potential benefit of SGLT2 inhibitors on cardiovascular mortality, DECLARE-TIMI 
58 trial showed that treatment with dapagliflozin reduced the risk of 
cardiovascular death or hospitalization for heart failure to a greater extent in 
patients with reduced ejection fraction (EF). Although novel pharmacotherapy is 
the current focus of intense research, there have been numerous studies on 
potential benefit of iron supplementation in ferropenic patients with heart 
failure. Another rapidly expanding area of research in the realm of heart 
failure is precision medicine and its impact on the development, progression, 
and treatment of heart failure. The field of heart failure is dynamic and with 
the influx of data from recent and ongoing trials, newer therapies with 
morbidity and mortality benefits in HFrEF are now available, nonetheless, much 
work is still needed.