Background pharmacological therapy in the ANTHEM‐HF: comparison to contemporary trials of novel heart failure therapies

• Published in: ESC Heart Failure 2019-10, Vol.6 (5), p.1052-1056
• Main Authors: Premchand, Rajendra K., Sharma, Kamal, Mittal, Sanjay, Monteiro, Rufino, Libbus, Imad, Ardell, Jeffrey L., Gregory, Douglas D., KenKnight, Bruce H., Amurthur, Badri, DiCarlo, Lorenzo A., Anand, Inder S.
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - pharmacology; Adrenergic beta-Antagonists - therapeutic use; Adult; Aged; Aminobutyrates - pharmacology; Aminobutyrates - therapeutic use; Angiotensin Receptor Antagonists - pharmacology; Angiotensin Receptor Antagonists - therapeutic use; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Autonomic nervous system; Autonomic Nervous System - drug effects; Autonomic Nervous System - physiopathology; Autonomic regulation therapy; Cardiac arrhythmia; Cardiovascular Agents - pharmacology; Cardiovascular Agents - therapeutic use; Drug Combinations; Ejection fraction; Female; Guideline‐directed medical therapy; Heart failure; Heart Failure - drug therapy; Heart Failure - physiopathology; Heart Failure - psychology; Heart rate; Humans; Ivabradine - pharmacology; Ivabradine - therapeutic use; Male; Middle Aged; Mineralocorticoid Receptor Antagonists - pharmacology; Mineralocorticoid Receptor Antagonists - therapeutic use; Nervous system; Neuromodulation; Original; Original s; Practice Guidelines as Topic - standards; Quality of Life; Stroke Volume - drug effects; Stroke Volume - physiology; Studies; Tetrazoles - pharmacology; Tetrazoles - therapeutic use; Treatment Outcome; Vagus nerve stimulation; Vagus Nerve Stimulation - methods; Ventricular Function, Left - drug effects; Ventricular Function, Left - physiology; Walk Test - methods; Walk Test - statistics & numerical data
• ISSN: 2055-5822; 2055-5822
• DOI: 10.1002/ehf2.12484

Aims Clinical trials of new heart failure (HF) therapies administer guideline‐directed medical therapy (GDMT) as background pharmacologic treatment (BPT). In the ANTHEM‐HF Pilot Study, addition of autonomic regulation therapy to GDMT significantly improved left ventricular function, New York Heart Association (NYHA) class, 6 min walk distance, and quality of life in patients with HF with reduced ejection fraction (HFrEF). A post hoc analysis was performed to compare BPT in ANTHEM‐HF with two other trials of novel HF therapies: the PARADIGM‐HF study of sacubitril–valsartan and the SHIFT study of ivadrabine. All three studies evaluated patients with HFrEF, and the recommendations for use of GDMT were similar. A left ventricular ejection fraction ≤40% was required for entry into ANTHEM‐HF and PARADIGM‐HF and ≤35% for SHIFT. NYHA 2 or 3 symptoms were required for entry into ANTHEM‐HF, and patients with predominantly NYHA 2 or 3 symptoms were enrolled in PARADIGM‐HF and SHIFT. Methods and results Data on BPT were obtained from peer‐reviewed publications and the public domain. Pearson's χ2 test was used to evaluate differences in proportions, and Student's unpaired t‐test was used to evaluate differences in mean values. The minimum period of stable GDMT required before randomization was longer in ANTHEM‐HF: 3 months vs. 1 month in PARADIGM‐HF and SHIFT, respectively. When compared with PARADIGM‐HF and SHIFT, more patients in ANTHEM‐HF received beta‐blockers (100% vs. 93% and 89%, P < 0.04 and P < 0.007) and mineralocorticoid receptor antagonists (75% vs. 55% and 61%, P < 0.002 and P < 0.03). More patients in PARADIGM‐HF received an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker than in ANTHEM‐HF or SHIFT (100% vs. 85%, P < 0.0001, and 100% vs. 91%, P < 0.001), which was related to PARADIGM's design. When beta‐blocker doses in ANTHEM‐HF and SHIFT were compared, significantly fewer patients in ANTHEM‐HF received doses ≥100% of target (10% vs. 23%, P < 0.02), and fewer patients tended to receive doses ≥50% of target (17% vs. 26%, P = 0.11). When ANTHEM‐HF and PARADIGM‐HF were compared, more patients in ANTHEM‐HF tended to receive doses ≥100% of target (10% vs. 7%, P = 0.36), and fewer patients tended to receive doses ≥50% of target (17% vs. 20%, P = 0.56). Conclusions Background treatment with GDMT in ANTHEM‐HF compared favourably with that in two other contemporary trials of new HF therapies. The minimum period of stable GDMT required befo