2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

Ponikowski, Piotr; Voors, Adriaan A.; Anker, Stefan D.; Bueno, Héctor; Cleland, John G.F.; Coats, Andrew J.S.; Falk, Volkmar; González-Juanatey, José Ramón; Harjola, Veli‐Pekka; Jankowska, Ewa A.; Jessup, Mariell; Linde, Cecilia; Nihoyannopoulos, Petros; Parissis, John; Pieske, Burkert; Riley, Jillian; Rosano, Giuseppe; Ruilope, Luís M.; Ruschitzka, Frank; Rutten, Frans H.; Meer, Peter van der

doi:10.1002/ejhf.592

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“…These therapies comprise the cornerstone of pharmacological chronic HF treatment. More recently, further progress has been made with the addition of an angiotensin receptor/neprilysin inhibitor (ARNI) as an alternative to ACE inhibitors, and ivabradine as an adjunct to maximally tolerated beta‐blocker therapy in patients in sinus rhythm 1, 23. However, these patients remain at high risk for acute decompensation, an event associated with a marked increase in mortality and HF recurrence either in the form of in‐hospital or post‐discharge WHF.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the urgent need to improve the outcomes of patients with AHF, only three therapies have gained regulatory approval in the last two decades: i.v. milrinone and nesiritide in the US and levosimendan in Europe 1, 2. Despite their approval, none of these drugs has demonstrated favourable effects on outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…Current treatment of AHF is based on drugs that have limited evidence of efficacy based on formal randomized controlled data. While diuretics have a Class I recommendation with a C level of evidence for the treatment of patients with congestion for symptom relief, other therapies such as nitrates have Class IIa recommendations with a B level of evidence 1. None of these therapies has an indication for improvement in clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…SBP >150 mmHg at the time of screening). The dose of nitrates allowed in RELAX‐AHF‐2 is clinically relevant and not particularly restrictive; an 80 kg person could be receiving up to 133 µg/min nitroglycerin or three times the dose achieved in VMAC,36 and over 6–10 times the recommended starting dose of the ESC guidelines 1…”

Section: Discussionmentioning

confidence: 99%

“…Acute heart failure (AHF) is the most common cause of hospitalization in patients 65 years and older 1, 2. In part due to the ageing of the population and more effective treatment of chronic heart failure (HF), its prevalence is expected to increase by 25% over the next 20 years 3 and the problem has expanded worldwide 4, 5.…”

Section: Introductionmentioning

confidence: 99%

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Serelaxin in addition to standard therapy in acute heart failure: rationale and design of the RELAX‐AHF‐2 study

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Voors

Ponikowski

et al. 2017

European J of Heart Fail

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Patients admitted for acute heart failure (AHF) experience high rates of in‐hospital and post‐discharge morbidity and mortality despite current therapies. Serelaxin is recombinant human relaxin‐2, a hormone with vasodilatory and end‐organ protective effects believed to play a central role in the cardiovascular and renal adaptations of human pregnancy. In the phase 3 RELAX‐AHF trial, serelaxin met its primary endpoint of improving dyspnoea through day 5 in patients admitted for AHF. Compared to placebo, serelaxin also reduced worsening heart failure (WHF) by 47% through day 5 and both all‐cause and cardiovascular mortality by 37% through day 180. RELAX‐AHF‐2 ( ClinicalTrials.gov NCT01870778) is designed to confirm serelaxin's effect on these clinical outcomes. RELAX‐AHF‐2 is a multicentre, randomized, double‐blind, placebo‐controlled, event‐driven, phase 3 trial enrolling ∼6800 patients hospitalized for AHF with dyspnoea, congestion on chest radiograph, increased natriuretic peptide levels, mild‐to‐moderate renal insufficiency, and systolic blood pressure ≥125 mmHg. Patients are randomized within 16 h of presentation to 48 h intravenous infusions of serelaxin (30 µg/kg/day) or placebo, both in addition to standard of care treatments. The primary objectives are to demonstrate that serelaxin is superior to placebo in reducing: (i) 180 day cardiovascular death, and (ii) occurrence of WHF through day 5. Key secondary endpoints include 180 day all‐cause mortality, composite of 180 day combined cardiovascular mortality or heart failure/renal failure rehospitalization, and in‐hospital length of stay during index AHF. The results from RELAX‐AHF‐2 will provide data on the potential beneficial effect of serelaxin on cardiovascular mortality and WHF in selected patients with AHF.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%