LAUSR

The sheer number of medical ailments that afflict humans far surpasses our ability to effectively alter the natural course of most diseases. Yet, modern evidence-based medicine has catapulted remarkable gains for both the prevention and chronic management of cardiovascular diseases. The recognition of smoking, hypertension, diabetes, and dyslipidaemia as strong modifiable atherosclerotic risk factors has slowly decreased rates of cardiovascular diseases and in turn have contributed to the overall improvement in population health. Nowhere is this more evident than in the management of chronic heart failure with reduced ejection fraction (HFrEF), where we now have over a dozen therapeutic options to improve quality of life and reduce morbidity and mortality1 (Figure 1). While a number of medical therapies – even after potentially promising signals in Phase II studies – failed to demonstrate benefits in large-scale trials in HFrEF, the benefits demonstrated in successful trials for chronic HFrEF have been reproduced in subsequent trials using other agents in the same pharmacologic class. These evidence-based medical therapies provide sequential incremental clinical benefits without noted heterogeneity across a multitude of subgroups of patients based on demographics, comorbidities, or severity of disease, enrolled in the landmark trials.1,2 Treatment benefits stratified by severity estimated using validated risk scores report relative risk reductions of similar magnitude for treatment compared to placebo without important heterogeneity.3,4 Although clinical trials may enrol a selective HFrEF patient population than those in routine clinical practice, similar relative risk reductions are observed in clinical effectiveness studies of registry populations with guideline-directed medical therapies, despite higher baseline risk and comorbidity burdens.5 In contrast to the success in demonstrating benefits with multiple medications for HFrEF, there has been consistent failure to identify therapies which improve outcomes for patients hospitalized with acute heart failure (AHF) or heart failure with