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Approximately 26 million people live with heart failure worldwide. University of Glasgow researchers have been instrumental in proving the value, in landmark clinical trials, of bisoprolol, candesartan and eplerenone — three of the four classes of drug that reduce mortality, reduce hospitalisation rates and improve quality of life for patients with heart failure. These trials led directly to revision of clinical guidelines on heart failure management globally (including in Europe, USA, UK, Australia and Canada, all published since 2008). The Glasgow researchers have established heart failure as a healthcare priority and encouraged the introduction of specialist heart failure nurses, saving the NHS an estimated £8 million per year. Collectively, these advances have transformed the treatment and survival rates of heart failure patients worldwide.
Our research with spironolactone has advanced treatment in heart failure. We conducted the first "proof of concept" study to show that spironolactone had beneficial cardiac effects in man. In patients with heart failure, we demonstrated that it reduced cardiac sympathetic activity and arrhythmias. Spironolactone was pioneered in Dundee as a treatment to reduce deaths in chronic heart failure. This treatment is now recommended (Level A evidence; Class I recommendation) for the treatment of symptomatic heart failure in all guidelines including the 2010 NICE guidelines. It is also now a standard in the 2010 NHS Quality Improvement Scotland standards.
Randomised placebo-controlled trials (RCTs) are the most robust way to demonstrate the effectiveness of medical therapies. The University of Glasgow's Robertson Centre for Biostatistics (RCB) is internationally renowned for its biostatistical input and leading roles on landmark RCTs of cardiovascular therapies. The findings of the BEAUTIFUL and SHIFT studies underpinned European and UK regulatory approval for a novel use of the heart-rate-lowering drug ivabradine, potentially preventing thousands of hospital admissions for heart failure every year. The IONA trial supported UK approval of generic versions of another heart drug (nicorandil), thereby enhancing cost-effectiveness for the NHS. The BEAUTIFUL, SHIFT, DOT-HF and CAPRICORN trials provided the evidence base for US, European and UK guideline recommendations, steering best practice for treatment of patients with heart disease worldwide.
Our research on brain/B-type naturietic peptide (BNP) has helped to diagnose both types of heart failure (systolic and diastolic heart failure) and to identify high-risk aortic stenosis patients for surgery. We were first to demonstrate the value of BNP as a biomarker for left ventricular systolic dysfunction, isolated diastolic dysfunction and for aortic stenosis. BNP testing is now recommended in Guidelines as a screening test for patients with suspected heart failure (Class I recommendation) and in the current European Society of Cardiology consensus statement for diagnosis of diastolic heart failure. The European Society of Cardiology Guidelines have also introduced BNP testing in the management of patients with aortic stenosis (Class IIb recommendation).
Patients with evidence of heart failure following acute myocardial infarction (AMI) have a particularly poor prognosis, with substantially increased risk of death and subsequent cardiovascular events. The Acute Infarct Ramipril Efficacy (AIRE) Randomised Controlled Trial (RCT) was an international trial designed and led by the University of Leeds. AIRE demonstrated, for the first time, that early treatment of patients with clinical evidence of heart failure following AMI with the angiotensin converting enzyme inhibitor (ACEI) ramipril significantly improved survival and quality of life compared with placebo treated patients. The strategy of early initiation of ACEI is now a cornerstone in the management of patients suffering from AMI, leading to a global improvement in post-AMI outcomes.
The research team at Bucks New University has provided the groundwork for a number of applications to use cardiac power output as a novel functional measurement in the clinical evaluation of patients with heart failure and other related diseases. It involved validating the measure, assessing its reliability and applying it to a group of patients with end-stage heart failure. The success of this procedure is now evidenced by the number of national and international clinical centres adopting cardiac power output as a key functional measurement.
Beta-blockers are now a worldwide mainstay of heart failure treatment recommended in all international guidelines for chronic heart failure: this is a reversal of previous practice since they were completely contraindicated in this condition up to the late 1990s. Imperial College researchers were pivotal in defining beta-adrenoceptor/beta-blocker mechanisms in failing human hearts and translating the benefits into clinical practice. Imperial College researchers designed and led the COMET and SENIORS beta-blocker trials for heart failure and the UK arm of the COPERNICUS trial. These studies helped establish beta blockers in modern heart failure management: these are now the 4th most commonly prescribed drugs worldwide.
Hull researchers conducted the key trial demonstrating that cardiac resynchronization therapy (CRT), a specialised type of pacemaker, significantly reduces morbidity and mortality and improves the quality of life of selected patients with heart failure. CRT has become a cornerstone of treatment for heart failure and a standard recommendation in clinical guidelines world-wide. Over a 5 year period about 40,000 people in the UK have had pacemakers implanted; about 8,000 of these patients would be projected to have died within 5 years if they had not received CRT. The world market for CRT devices is projected to grow to $2.8 billion annually by 2015.
The Acute Infarct Ramipril Efficacy (AIRE) multicentre international trial, conceived, designed, led and coordinated by Leeds was the first to show that use of early angiotensin converting enzyme Inhibitor (ACEI) therapy in patients with signs and symptoms of heart failure after an acute myocardial infarction (AMI) is associated with significantly longer survival and better quality of life. Further Leeds research showed the beneficial effects persisted long-term. The strategy of early initiation of ACEI is now a fundamental and routine part of the management of patients after AMI and has contributed to better survival and quality of life for patients around the world.
Atrial fibrillation (AF) is the most common chronic heart rhythm disorder, afflicting 1-2% of the total population and up to 10% of individuals aged over 70 years. There is an urgent need for safer and more effective therapies to prevent and treat AF. University of Glasgow researchers have played leading roles in studies that have identified strategies which prevent AF, improved the safety of AF therapies, and proved the clinical efficacy of a novel anticoagulant to reduce the risk of stroke (the major consequence of AF). The findings have rapidly informed recommendations in international guidelines, prompted regulatory amendments of AF therapies and changed prescribing practices. These advances will affect the estimated 12 million Europeans and Americans suffering from AF.