Summary of the impact

Over the past ten years, the prescription of cholesterol-lowering statins has soared and they are now the most prescribed drugs in the UK and the US. However, this has raised concerns about inappropriate prescribing. University of Glasgow research has been pivotal in addressing this issue and has triggered revision of major international guidelines to stratify patients in the general population for statin therapy and guide statin use in the rheumatoid arthritis patient population. The identification of a statin-associated risk for diabetes prompted the European Medicines Agency and the US Food & Drug Administration to revise safety labelling for all classes of statins. This risk is now communicated to the 27 million patients in the UK and US who are prescribed statins.

Summary of the impact

The Collaborative Atorvastatin Diabetes Study (2004), led by researchers at the University of Manchester (UoM), established the efficacy of statin therapy in the prevention of atherosclerotic cardiovascular disease (CVD) among patients with diabetes. The research challenged the previously held view that, since CVD risk is markedly raised in people with diabetes even when blood cholesterol levels are normal, statins were unlikely to be beneficial for this group. These key findings have informed clinical guidelines governing the use of statin therapy in the UK (NICE, SIGN) and internationally (American Heart Association and the American Diabetes Association, ESC, EAS), ensuring that statins are now considered for all diabetic patients.

Summary of the impact

Studies coordinated by the University of Oxford's Clinical Trial Service Unit (CTSU) within the Nuffield Department of Population Health (NDPH) have strongly influenced the labelling of statin medication internationally, treatment guidelines, and the resulting changes in prescribing have contributed to reductions in mortality and morbidity from heart attack and ischaemic stroke in many countries. CTSU's randomised trials and meta-analyses of trials have shown that lowering low-density lipoprotein (LDL) cholesterol safely reduces the risk of heart attacks, strokes and revascularisation procedures in a wide range of people, and work conducted in collaboration with the NDPH's Health Economic Research Centre has provided clear evidence of cost-effectiveness of statins.

Summary of the impact

University of Sheffield research which evaluated the clinical and cost-effectiveness of statins for the primary and secondary prevention of cardiovascular events has directly led to an additional 3.3 million people in England and Wales becoming eligible for this treatment. Statins have been shown to reduce the risk of future cardiovascular events, such as heart attacks and stroke.

Guidance on statin prescribing in England and Wales, issued by the National Institute for Health and Care Excellence (NICE) Appraisal Committee in January 2006 was informed by our research report. Following this guidance the number of patients receiving statins has increased year on year with the number of prescriptions increasing by 29% between 2007 and 2011, enabling these patients to benefit from reduced risk of heart attacks and stroke and CVD related deaths.

Summary of the impact

The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT; Co-Chairman, Professor Sever) was an investigator designed and led multinational study in which different blood pressure-lowering and lipid-lowering treatment strategies were investigated in an attempt to define optimal programmes for intervention to prevent cardiovascular disease in hypertensive subjects. The outcomes of both the antihypertensive arm and the lipid arm of the trial defined the benefits of more contemporary treatments for hypertensive subjects, including calcium channel blockers, angiotensin converting enzyme inhibitors and statins, which have been incorporated into national and international guidelines (including NICE), and have impacted on current clinical practice in the prevention of cardiovascular disease worldwide.

Summary of the impact

Caulfield co-led and was a principal investigator (PI) on Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Hitman co-led and was a PI on Collaborative AtoRvastatin Diabetes Study (CARDS). These studies dramatically changed national and international guidance for diabetes, hypertension and cholesterol, leading to widespread and far-reaching changes in management of common and potentially fatal risk factors. For example, the proportion of hypertensive patients in England with good BP control (<140/90) rose from 52% in 2006 to 62% in 2011; the mean total cholesterol level of the population has fallen by 0.5 Mmol/L between 1998 and 2011.

Summary of the impact

Over the past 20 years, the University of Oxford's Clinical Trial Service Unit (CTSU), within the Nuffield Department of Population Health (NDPH), has conducted some of the world's largest trials and collaborative meta-analyses of trials of antiplatelet therapy, including aspirin, that have together had a major ongoing and incremental impact on the treatment and prevention of cardiovascular disease. They have helped ensure that antiplatelet therapy is widely used both in the acute care of patients with heart attacks and for the secondary prevention of heart attacks and strokes in high-risk patients. This research has been recognised as the gold standard for international guidelines, and has been instrumental in changing prescribing labelling for aspirin.

Summary of the impact

Stroke is the leading cause of disability and a major cause of death in the developed world. Hypertension (high blood pressure) is the single most important modifiable risk factor for stroke, contributing to around 50% of all events. University of Glasgow researchers have played lead roles in the design, conduct and analysis of pivotal clinical trials on treatment regimens for hypertension. These research findings have informed European and UK hypertension and stroke guidelines, advancing treatment strategies, and contributed to the observed ~25% reduction in the incidence of primary (first) and secondary (recurrent) stroke.

Summary of the impact

An eight year MRC-funded clinical trial led by the University of Dundee and run throughout Scotland (16 hospitals, 188 GP Surgeries) exploring aspirin in diabetes for primary cardiovascular event prevention, where clinical practice had evolved without evidence.

• NHS: Implementation of results in general practices, hospitals, and Health Boards globally, by ceasing to prescribe aspirin as primary prevention in diabetes.
• Policy: Resulted in major changes to international Guidelines globally e.g. American Diabetes Association Guidelines, Australian, New Zealand and Canadian Guidelines and Scottish Intercollegiate Guideline Network (SIGN).
• Improved Patient Care and Health Outcomes: Reduction in aspirin prescribing with decrease in adverse events, reduction in concomitant proton pump inhibition prescribing.
• Internationalisation: Implementation worldwide, by doctors and pharmacists with reports in lay publications, radio programmes, TV interviews and patient targeted websites.

Summary of the impact

Impact: Health and welfare; a clinical trial demonstrated that statin therapy is ineffective in aortic stenosis; this informed international guidelines and changed clinical practice.

Significance: Unnecessary statin therapy is avoided in up to 500,000 people in the UK alone, saving the NHS £169M p.a. Known statin side-effects of myalgia or hepatic dysfunction are avoided in 30,000 patients.

Beneficiaries: Patients with aortic stenosis; the NHS and healthcare delivery organisations, the economy.

Attribution: Newby and Boon, UoE, undertook the first investigator-led randomised controlled trial of statin therapy in aortic stenosis: the SALTIRE trial.

Reach: Aortic stenosis affects 2% of people over 65. The SALTIRE trial results informed European and N American guidelines and have impacted the treatment of millions of people globally.