HFREF Pharmacological Treatment Sequencing: The Traditional Approach

The traditional approach to sequencing

This approach respects the historical introduction of drugs studied and proven by randomized clinical trials (RCTs) and has its use approved by all guidelines. It is important to note that all RCTs on heart failure with reduced ejection fraction (HFrEF) have used this sequencing approach, and when a new drug is tested, it is added to optimized standard therapy. This reinforces the need to maintain triple therapy with a beta-blocker (BB), an angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB), and a mineralocorticoid receptor antagonist (MRA). Therefore, this triad is recommended as a key therapy for HFrEF unless drugs are contraindicated or not tolerated.

Angiotensin receptor-neprilysin inhibitors (ARNis; sacubitril/valsartan) should replace ACEis in patients who remain symptomatic despite the triad and may also be considered first-line therapy instead of ACEis ( ). The maximum recommended doses (MRDs) of these drugs are described in the Brazilian Society of Cardiology guidelines.

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