Home > Cardiology > HFA 2021 > Late-Breaking Trials > Omecamtiv mecarbil might be less effective in patients with atrial fibrillation or flutter

Omecamtiv mecarbil might be less effective in patients with atrial fibrillation or flutter

Presented by
Prof. Scott Solomon, Brigham and Women’s Hospital, MA, USA
Conference
HFA 2021
Trial
GALACTIC-HF
Heart failure (HF) patients with atrial fibrillation or flutter (AFF) at baseline had less treatment benefit from therapy with omecamtiv mecarbil than patients without AFF at baseline. According to post-hoc analyses of the GALACTIC-HF trial, this effect was significantly more pronounced in patients treated with digoxin.

“The myosin activator omecamtiv mecarbil augments cardiac sarcomere function by facilitating the actin-myosin interaction, resulting in an increased contractile force,” said Prof. Scott Solomon (Brigham and Women’s Hospital, MA, USA) [1]. In the GALACTIC-HF trial (NCT02929329), omecamtiv mecarbil reduced the risk of a composite of cardiovascular death or first HF event in patients with HF and reduced ejection fraction [2]. Prof. Solomon explained that “AF is very common in patients with HF and contributes to morbidity and mortality. This has not modified the treatment effect of renin-angiotensin-aldosterone inhibitors but may modify the treatment effect of β-blockers. It was one of 2 factors that modified the efficacy of omecamtiv mecarbil. In a subgroup analysis of GALACTIC-HF, it was less effective in patients with AF at baseline.”

Thus, the objective of the current analysis was to assess whether the effectiveness of omecamtiv mecarbil is modified by baseline AFF. Patients included in the GALACTIC-HF trial had chronic HF (NYHA II-IV), left ventricular ejection fraction ≤35%, elevated B-type natriuretic peptide(BNP)/N-terminal pro B-type natriuretic peptide (NT-proBNP) and were managed with standard HF therapies.

Of the GALACTIC-HF participants, 2,245 patients had AFF at baseline. Compared with patients without AFF (n=5,987), they were older, were more likely to have a history of hypertension or stroke, more likely to be in a higher NYHA class, and have a higher NT-proBNP concentration. Both groups were similarly well treated, but substantially more patients with AFF at baseline were treated with digoxin.

Greater treatment effect in patients without AFF
AFF modified the treatment effect of omecamtiv mecarbil in both the primary composite endpoint (Pinteraction=0.012) as well as in secondary endpoints such as CV death (Pinteraction=0.002), all-cause death (Pinteraction<0.001), and HF hospitalisation (Pinteraction=0.12; see Figure). “Treatment effect of omecamtiv mecarbil was greater in patients without AFF,” Prof. Solomon explained. This effect remained after multivariable adjustment.

Figure: Atrial fibrillation/flutter modifies treatment effect of omecamtiv mecarbil [1]

 

Because of notable differences in pharmacology background therapy, post-hoc analyses were performed to find possible explanations for this difference. “We found that the treatment effect modification for the primary outcome by AFF was significantly more pronounced in patients using digoxin compared with non-users,” Prof. Solomon said. Plasma concentrations of omecamtiv mecarbil at 6 weeks were similar in those taking and those not taking digoxin (median 286 vs 280 mg/mL; P=0.78). In patients in whom digoxin doses were known, they were similar in both treatment arms. In patients without AFF and in healthy volunteers, there was no interaction with digoxin.

“So far, we do not have a smoking gun, we do not know what is responsible for this interaction,” Prof. Solomon said in the discussion. While the presence of AFF at baseline was a prespecified subgroup, the use of digoxin was not. These additional analyses were data-driven and should be considered hypothesis generating. Despite this limitation, he concluded that these findings suggest caution when treating patients with AFF with both digoxin and omecamtiv mecarbil.



      1. Solomon S, et al. Influence of Atrial Fibrillation on Efficacy of Omecamtiv Mecarbil in Heart Failure: The GALACTIC-HF Trial. LBT 1, Heart Failure and World Congress on Acute Heart Failure 2021, 29 June–1 July.
      2. Teerlink JR, et al. JACC Heart Fail 2020;8:329-40.

 

Copyright ©2021 Medicom Medical Publishers



Posted on