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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.
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.
Academics from the University of Hull led a programme of research that demonstrated for the first time that telehealth (the use of technology to support remotely the delivery of healthcare) could improve clinical outcomes for patients with heart failure.
The University's Centre for Telehealth is now recognised internationally as a leader in this area, has been identified as an exemplar of best practice, and is highly influential in developing national and European guidelines. The Centre's activities have supported the development of telehealth services for thousands of patients within the UK and Europe. It is also a key player in initiatives devoted to the enhancement of telehealth services through supporting industry and training of the health and social care workforces.
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.
Pulmonary arterial hypertension (PAH) is a fatal disease that typically affects women in their childbearing years. Professor Wilkins led a research team at Imperial College that identified phosphodiesterase type 5 (PDE5) as a drug target in the lungs of patients with PAH. Imperial validated the target in cell and animal models and demonstrated proof in patients that Sildenafil, a PDE5 inhibitor, was an effective treatment for PAH. Professor Wilkins conducted a clinical study to compare the effect of oral Sildenafil with Bosentan, the only other available oral therapy for PAH at the time. This study was the first, and remains the only, head-to-head study of two treatments for PAH. Sildenafil demonstrated comparable efficacy, had a greater effect on reducing cardiac mass (an integrated measure of heart work) and was well tolerated.
Sildenafil is now the most commonly prescribed drug for PAH. It is the most cost-effective, as judged by a technology appraisal initiated by NICE. National and international guidelines recommend Sildenafil as a first line treatment for patients in functional classes II and III pulmonary hypertension. Worldwide sales of sildenafil (Revatio®) for the management of PAH were $500m in 2010. With the expiration of the patent the cost of treatment will fall further.
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.
The development of a cardiac magnetic resonance technique at Imperial College and Royal Brompton Hospital to quantify myocardial iron concentration has resulted in the early identification of thalassaemia major patients at risk of heart failure and targeted cardiac treatment with a hitherto little used iron chelator, deferiprone, following randomised controlled trials of efficacy. Since 2008 these advances have resulted in a 71% reduction in cardiac death from myocardial siderosis in thalassemia major in the UK.