Comorbid AF does not influence effects of rapid GDMT uptitration in acute HF

A post-hoc STRONG-HF analysis showed rapid GDMT uptitration during and after hospitalization for acute HF was feasible and safe and improved clinical outcomes compared with usual care, regardless of a history of AF/atrial flutter.

This summary is based on the publication of Farmakis D, Davison B, Fountoulaki K, et al. - Rapid Uptitration of Guideline-Directed Medical Therapies in Acute Heart Failure With and Without Atrial Fibrillation. JACC Heart Fail. 2024 Nov;12(11):1845-1858. doi: 10.1016/j.jchf.2024.06.010

Introduction and methods

Background

In patients with acute HF (AHF), atrial fibrillation or flutter (AFF) may be a trigger for decompensation and can further complicate their disease course and management [1]. Previously, the STRONG-HF (Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies) trial showed that initiation and rapid uptitration of GDMTs before and shortly after discharge combined with close follow-up was safe and improved clinical outcomes in hospitalized HF patients [2]. However, it is uncertain whether this is also the optimal treatment plan for AHF patients with concomitant AFF.

Aim of the study

In a post-hoc analysis of the STRONG-HF trial, the authors investigated whether rapid GDMT uptitration before and after discharge is feasible, safe, and beneficial in AHF patients with and with no AFF.

Methods

The STRONG-HF trial was an international, multicenter, open-label, parallel-group RCT in which 1078 patients admitted to the hospital for AHF were randomized ≤2 days before the anticipated discharge to high-intensity care (HIC) or usual care. The HIC strategy comprised uptitration of oral HF medications (RAASi (ACEi/ARB/ARNI), beta-blocker, and MRA) to half optimal doses at randomization and to full doses at 2 weeks.

In addition, these patients had follow-up visits with comprehensive evaluation at 1, 2, 3, and 6 weeks postdischarge. In the current analysis, AFF was defined as any history of ECG evidence of AF or atrial flutter. Of the total study population, 496 patients (46%) had a history of AFF and 581 (54%) had no such history.

Outcomes

The study’s primary endpoint was a composite outcome of HF hospital readmission or all-cause mortality at 180 days. Other endpoints included the individual components of the primary endpoint. The frequencies of adverse events and serious adverse events at 90 days were also analyzed.

Main results

• In the overall study population, the incidence of the primary endpoint of HF readmission or all-cause mortality at 180 days was similar in patients with and with no AFF (Kaplan–Meier estimate: 21.2% vs. 17.9%; adjusted HR: 1.07; 95%CI: 0.77–1.48; P=0.7017).
• The rate of the primary endpoint was lower in patients randomized to the HIC strategy compared with those assigned to UC, both in patients with AFF (adjusted HR: 0.75; 95%CI: 0.48–1.19) and those with no AFF (adjusted HR: 0.50; 95%CI: 0.31–0.79; P for interaction=0.2107).
• AFF status also did not affect the rates of the other endpoints (both P for interaction>0.05).
• The average percent optimal dose of the 3 GDMTs achieved in the HIC arm by day 90 was similar in patients with and with no AFF, reaching ~80% of the optimal dose (average absolute difference between AFF and non-AFF patients: –0.81%; 95%CI: –3.51% to 1.89%; P=0.5543).
• Although adverse events were generally more frequent in the HIC group than the UC group, the proportions of patients with adverse events or serious adverse events did not differ by history of AFF.
• The AFF type (permanent, paroxysmal, or persistent) did not affect the optimal dose percentages, clinical outcomes, or adverse event rates.

Conclusion

This post-hoc analysis of the STRONG-HF trial showed almost half of the patients hospitalized for AHF had a history of AFF. Rapid GDMT uptitration before and early after discharge was feasible and safe and reduced the incidence of HF readmission or all-cause mortality at 180 days compared with UC, regardless of the presence or type of AFF. In addition, the proportion of patients achieving optimal GDMT doses was similar between participants with and with no AFF.

The higher incidence of adverse events in the HIC arm compared with the UC arm, regardless of a history of AFF, “emphasizes the importance of the close monitoring of patients during the vulnerable transition period,” according to the authors.

Find this article online at JACC Heart Fail.

References

1. Gorenek B, Halvorsen S, Kudaiberdieva G, et al. Atrial fibrillation in acute heart failure: a position statement from the Acute Cardiovascular Care Association and European Heart Rhythm Association of the European Society of Cardiology. Eur Heart J Acute Cardiovasc Care. 2020;9:348–357.
2. Mebazaa A, Davison B, Chioncel O, et al. Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial. Lancet. 2022;400:1938–1952.