LAUSR

Since 1980, treatment of heart failure (HF) with reduced ejection fraction (HFrEF) has steadily evolved to stepwise combination of angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) inhibition, beta-blockade (BB), and mineralocorticoid receptor antagonism (MRA).1 This combination has been referred to in HF guidelines as guideline-directed medical therapy (GDMT). More recently, landmark studies have proven efficacy of sinus node inhibition (If), angiotensin receptor–neprilysin inhibition (ARNi, a replacement for ACEi/ARB) and sodium–glucose co-transporter 2 inhibition (SGLT2i) added to GDMT.2–4 These trials have been based upon administration of new medications at target doses (TD) in carefully selected populations already receiving optimally delivered GDMT. Heart failure guideline have been written from the perspective of conditions noted in clinical trials where stable HFrEF cohorts were followed closely. The resulting recommendations strongly emphasized (a) complete up-titration of existing therapy to the target (or maximally tolerated) dose of prior to introduction of new therapies, and (b) gradual addition of medications in a linear fashion. Indeed, of all national or international HF guidelines, only one currently advocates initial MRA along with ACEi/BB, with titration and further assessment recommended prior to addition of newer therapies.5 This approach has led to unanticipated difficulties upon translation to the real world, where issues of comorbid conditions, access to care, and drug tolerability combine for a low rate of optimal GDMT, and resultant delay of initiation of new therapies.6 Both problems contribute to suboptimal outcomes. Is this emphasis of titration over initiation justified? Adherence to this model will inevitably delay initiation of new therapies if dose