Tag Archives: PARADIGM-HF

Landmark trials in heart failure – 30 years from CONSENSUS With 2017 marking the 30th year since the publication of CONSENSUS,1 which first reported a reduction in mortality with enalapril versus placebo in patients with advanced heart failure (HF), the BCS held a dedicated session to review the seminal clinical trials and advances in chronic heart failure management in this period. Dr Rosita Zakeri (Royal Brompton Hospital, London) reviewed this session for us and spoke to the BJC afterwards. Rosita Zakeri The era of vasodilator therapy for heart failure began in the 1990s. Professor Karl Swedberg (University of Gothenberg, Sweden) began

Targeting uric acid Dr Richard Crawley (Portsmouth Hospitals NHS Trust) The conference’s keynote lecture, delivered by Professor Austin Stack (University Hospital, Limerick, Ireland), homed in on the idea that serum uric acid directly contributes to increased cardiovascular disease. This was shown in his team’s work published in 2013,1 which used retrospective data to identify a direct correlation between raised serum uric acid concentrations and increased risk of developing cardiovascular disease. This, therefore, begs two questions: Firstly, does uric acid directly cause vascular endothelial damage, contributing to acute renal dysfunct

Sacubitril/valsartan (Entresto™, Novartis), the first angiotensin receptor blocker (ARB) and neprilysin inhibitor (NEP) combination – known as an angiotensin-receptor-neprilysin inhibitor (ARNI) – has recently been approved by the National Institute for Health and Care Excellence (NICE) in the treatment of patients with chronic heart failure.1 The guidance, largely based on results from the landmark PARADIGM- HF study,2 recommends sacubitril/valsartan as an “option” for symptomatic patients (New York Heart Association [NYHA] class II– IV) who have an ejection fraction of 35% or less and are established on a “stable dose” of an

Background Heart failure, a constellation of signs and symptoms in the presence of abnormal cardiac function, continues to represent a significant health problem within the UK, and, indeed, the wider developed world. In 2011, one in nine death certificates in the United States recorded heart failure as a contributing cause, and it was ascribed to being the direct underlying cause in 20% of cases.1 The current prevalence estimate for heart failure in the developed world is approximately 2%, which is a significant proportion of adults in industrialised society.2 Van Reit and colleagues have demonstrated from a systematic analysis of 25 study po

Introduction An acute pathological insult to the heart leads to a reduction in cardiac output (i.e. any cause of left ventricular systolic dysfunction [LVSD]), which activates a series of innate protective mechanisms. In the short term, activation of neurohumoral systems aim to preserve central arterial pressure and thereby vital organ perfusion, and include the sympathetic nervous system (SNS) and the renin–angiotensin–aldosterone system (RAAS). The net main effects of this process are: i) vasoconstriction; ii) sodium and water retention by the kidneys. While in the acute setting these adaptive responses may be beneficial, long-term over

The evidence in heart failure and reduced left ventricular ejection fraction PARADIGM-HF1 was a double-blind, randomised-controlled trial in which 8,442 patients with chronic symptomatic heart failure (New York Heart Association [NYHA] class II–IV) and a reduced left ventricular ejection fraction (LVEF) <40% (changed to ≤35% during the course of the study) were randomised to receive enalapril (10 mg twice daily) or sacubitril/valsartan (200 mg twice daily)*. Entry criteria also included a raised natriuretic peptide (NP) level (brain natriuretic peptide [BNP] ≥150 pg/ml or N-terminal proBNP [NTproBNP] ≥600 pg/ml, although for patien

Introduction A patient who seems to be doing well on conventional treatment will naturally be surprised and probably discomforted by the suggestion that his or her treatment should be changed, especially if this means an extra visit or two to the doctor or nurse, along with blood pressure checks and the taking of blood samples (and maybe the doctor or nurse looking after the patient might have similar thoughts!). Of course, those familiar with heart failure will know that the idea that a patient with heart failure is ‘doing well’ (or is ‘stable’) is a myth and that there is a high rate of disease progression, even with the currently b

Introduction Heart failure, if left untreated, has a worse prognosis than the majority of cancers. Yet with the best possible treatment − most of which can and possibly should be delivered in primary care − the one-year mortality can be as low as 10%. Earlier articles in this supplement have described how beta blockers, angiotensin-converting enzyme (ACE) inhibitors and mineralocorticoid receptor antagonists (MRAs) offer significant incremental survival benefits to patients with heart failure and reduced ejection fraction (HFREF) that can be further augmented by device therapy. Consider: an implantable cardioverter defibrillator (ICD) in

The 2016 guidelines include for the first time the new drug sacubitril/valsartan (previously known as LCZ696). This is the first drug in the class of angiotensin receptor neprilysin inhibitors (ARNIs) and was shown in the PARADIGM-HF trial to be superior to the angiotensin-converting enzyme (ACE) inhibitor enalapril for reducing the risk of death and hospitalisation in patients with heart failure with reduced ejection fraction (HFREF) who met strict inclusion and exclusion criteria. Professor Piotr Ponikowski (Chairperson of the ESC Guidelines Task Force), said: “The issue of how to include LCZ696 in the treatment algorithm generated a lot

Approval for new heart failure treatment A breakthrough drug for the treatment of chronic heart failure is now available in the UK.  The new drug sacubitril/valsartan (Entresto®, Novartis) has been approved for the treatment of adults with symptomatic heart failure with reduced left ventricular ejection fraction (HFREF). Sacubitril/valsartan – the first drug in the angiotensin receptor neprilysin inhibitor (ARNI) class of drugs – was found to be superior to an evidence-based dose of the angiotensin-converting enzyme (ACE) inhibitor, enalapril, in the PARADIGM-HF study, the largest heart failure study conducted to date. PARADIGM-HF (Pros