Sequencing Quadruple Therapy for Heart Failure with Reduced Ejection Fraction: Does It Really Matter?

Jiun-Ruey Hu; Alexandra N Schwann; Jia Wei Tan; Abdulelah Nuqali; Ralph J Riello; Michael H Beasley

doi:10.1016/j.hfc.2024.06.004

Sequencing Quadruple Therapy for Heart Failure with Reduced Ejection Fraction: Does It Really Matter?

Heart Fail Clin. 2024 Oct;20(4):373-386. doi: 10.1016/j.hfc.2024.06.004.

Authors

Jiun-Ruey Hu¹, Alexandra N Schwann², Jia Wei Tan³, Abdulelah Nuqali⁴, Ralph J Riello⁵, Michael H Beasley⁶

Affiliations

¹ Clinical and Translational Research Accelerator, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: https://twitter.com/ruey_hu.
² Department of Internal Medicine, Yale New Haven Hospital, P.O. Box 208030, New Haven, CT, 06520-8030, USA. Electronic address: https://twitter.com/aschwann212.
³ Division of Nephrology, Stanford University School of Medicine, 780 Welch Road, Palo Alto, CA 94304, USA. Electronic address: https://twitter.com/jiiiiawei.
⁴ Clinical and Translational Research Accelerator, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: https://twitter.com/AbdulelahNuqali.
⁵ Clinical and Translational Research Accelerator, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: https://twitter.com/ralphadelta.
⁶ Clinical and Translational Research Accelerator, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: [email protected].

PMID: 39216923
DOI: 10.1016/j.hfc.2024.06.004

Abstract

The conventional sequence of guideline-directed medical therapy (GDMT) initiation in heart failure with reduced ejection fraction (HFrEF) assumes that the effectiveness and tolerability of GDMT agents mirror their order of discovery, which is not true. In this review, the authors discuss flexible GDMT sequencing that should be permitted in special populations, such as patients with bradycardia, chronic kidney disease, or atrial fibrillation. Moreover, the initiation of certain GDMT medications may enable tolerance of other GDMT medications. Most importantly, the achievement of partial doses of all four pillars of GDMT is better than achievement of target dosing of only a couple.

Keywords: Beta blockers; Guideline-directed medical therapy; Heart failure with reduced ejection fraction; Mineralocorticoid receptor antagonists; Renin–angiotensin aldosterone system inhibitors; Sequence; Sodium–glucose cotransporter 2 inhibitors; Tolerability.

Publication types

Review

MeSH terms

Angiotensin Receptor Antagonists / therapeutic use
Angiotensin-Converting Enzyme Inhibitors / therapeutic use
Drug Therapy, Combination
Heart Failure* / drug therapy
Heart Failure* / physiopathology
Humans
Stroke Volume* / drug effects

Substances

Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors