Acute Heart Failure: Lessons Learned, Roads Ahead

Q: What is the clinical evidence from this study?

Study design: Review. Population: Acute heart failure. Intervention: Investigational therapies (e.g., vasodilators, inotropes) vs. Placebo or standard care.

Roberto Ferrari; Héctor Bueno; Ovidiu Chioncel; John G.F. Cleland; Wendy Gattis Stough; Maddalena Lettino; Marco Metra; John Parissis; Fausto J. Pinto; Piotr Ponikowski; Frank Ruschitzka; Luigi Tavazzi

doi:10.1002/ejhf.1169

March 8, 2018European Journal of Heart FailureOpen Access

Acute Heart Failure: Lessons Learned, Roads Ahead

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Key result

Mega-trials of acute heart failure therapies have not improved survival, with RELAX-AHF-2 showing no difference in 180-day cardiovascular mortality for serelaxin vs placebo (8.7% vs 8.9%; P=0.39).

Key Points

To examine why recent large-scale randomized trials in acute heart failure failed to improve long-term outcomes and to identify pathways for refining trial design and clinical management.
Reviewed clinical evidence and pathophysiological concepts from major prospective randomized trials evaluating novel acute heart failure therapeutics, with a focus on vasodilator trials including RELAX-AHF-2 and TRUE-AHF.
Analyzed clinical trial methodologies, including patient selection criteria, treatment timing, phenotypic heterogeneity, and the selection of clinical endpoints.
In TRUE-AHF (N=2,157), a 48-hour infusion of ularitide did not significantly reduce long-term cardiovascular mortality compared to placebo (21.7% vs. 21.0%; HR 1.03, 96% CI 0.85–1.25, P=0.75).
In RELAX-AHF-2 (N=6,545), serelaxin infusion failed to significantly lower 180-day cardiovascular mortality compared to placebo (8.7% vs. 8.9%, P=0.39) or worsening heart failure within 5 days (6.9% vs. 7.7%, P=0.10).
Short-term 48-hour drug infusions show limited potential to alter long-term survival due to marked patient heterogeneity, non-cardiac precipitating causes, and regional differences in standard heart failure care.

Structured PICO

P

Population

Patients with acute heart failure

I

Intervention

Acute heart failure therapies (including vasodilators such as serelaxin and ularitide, and inotropes)

C

Comparator

Placebo or standard care

The consistent failure of acute heart failure mega-trials to improve survival or major outcomes highlights the need for better patient phenotyping and targeted therapeutic strategies.

Limitations

Heterogeneity in patient phenotypes and precipitants of rehospitalization
Geographical differences in hospital admission, treatment approaches, and discharge practices
Problematic clinical trial endpoints requiring large sample sizes and long-term follow-up
Heterogeneity in precipitants of rehospitalization and mechanisms of death

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Implication

Acute HF mega-trials warrant therapeutic caution; leaves open whether refined phenotyping will enable targeted success.

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Cite This Study

Ferrari et al. (2018) conducted a review in Acute heart failure. Investigational therapies (e.g., vasodilators, inotropes) vs. Placebo or standard care was evaluated. Mega-trials of acute heart failure therapies have not improved survival, with RELAX-AHF-2 showing no difference in 180-day cardiovascular mortality for serelaxin vs placebo (8.7% vs 8.9%; P=0.39).

synapsesocial.com/papers/6a8c1c125ef9ff12d7895f55 https://doi.org/10.1002/ejhf.1169

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Acute Heart Failure: Lessons Learned, Roads Ahead

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Acute Heart Failure: Lessons Learned, Roads Ahead

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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