Victims of Success in Failure

ultiple successful clinical trials have defined the medical treatment of heart failure (HF) with reduced ejection fraction (HFrEF). Trials in the past century established angiotensin-converting enzyme (ACE) inhibitors, blockers, and mineralocorticoid receptor antagonists as the foundational therapies in HFrEF. The past decade brought more success with ivabradine, the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan, the sodium glucose cotransporter-2 inhibitors dapagliflozin and empagliflozin, as well as the soluble guanylase cyclase stimulator vericiguat. This success has led to new challenges in clinical implementation, rising costs, and high pill burdens for patients with HFrEF, who are increasingly multimorbid and elderly. An analysis of the Get With The Guidelines-HF registry showed that to be compliant with HF guidelines, 50% patients hospitalized with HF needed to start at least 1 new HF-related medication and a quarter needed >1 by discharge; these figures did not include medications for other comorbidities or newer therapies (data limited to before 2013). 1 Although polypharmacy is challenging, it is still superior to not having treatment options or not prescribing the best available evidence-based treatment. In fact, the availability of multiple effective medical options represents important progress for treating patients with HFrEF. However, we need to acknowledge and provide guidance for clinicians faced with decisions about how best to prioritize and sequence multiple therapies.