Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Accept all cookies Reject all non-essential cookies Find out more

Vascular Meta-Analyses

Meta-analysis is a statistical technique for combining the findings of randomised trials which have addressed the same or a similar scientific question. This programme of meta-analyses aims to determine in detail, for a wide range of individuals, the benefits and risks of several of the most important drugs used for the treatment and prevention of cardiovascular disease.

In each meta-analysis, after identifying randomised trials relevant to the particular question of interest, we set up a collaboration among the principal investigators and trial sponsors, and a secretariat coordinates the collection of individual participant data (IPD), data checking, analysis and publication. In each case, new trial evidence is incorporated as it is published, and new analyses are published as the data mature.

Individual participant data often provide a more accurate understanding of treatment effects and disease mechanisms. In particular, they allow assessment of the effects of a drug on: particular outcomes (such as distinguishing between atherosclerotic and non-atherosclerotic cardiac events) defined similarly in each trial; on particular types of trial participants (for example the effects of statins in women, the elderly or those with chronic kidney disease), and over time, which often allows the net effects of treatment to be understood in terms of benefits and hazards occurring on different timescales.

Our work on meta-analysis of drugs with effects on vascular disease include collaborative meta-analyses concerned with the effects of antiplatelet drugs, such as aspirin, the effects of lowering blood cholesterol with statins, the benefits and risks of recombinant tissue plasminogen activator (rt-PA) for acute ischaemic stroke, as well as the adverse cardiovascular effects of non-steroidal anti-inflammatory drugs (NSAIDs), and the potentially beneficial effects of gastroprotectant drugs at reducing the risk of peptic ulcer bleeding. Our findings have been widely cited, have influenced treatment guidelines and drug labelling, and are having a major impact on public health. The meta-analyses have also helped to highlight outstanding uncertainties that require new randomised trials.

 

 

 

Programme Leader

Programme

Vascular disease meta-analyses

We coordinate the Cholesterol Treatment Trialists’ (CTT) Collaboration which has assembled a database of individual participant data from 28 trials of statin therapy including a total of 175,000 people, and has led an improved understanding of the effects of statin therapy on cardiovascular disease in a wide range of people, including those at increased risk and those without known disease (i.e for primary prevention). Our current work is designed to provide more reliable information on the safety of statin therapy.  In order to do this we have collected all adverse event data recorded in these trials (which had not previously been sought from collaborators), and our analyses of such data will allow us to assess whether statins have any definite effects on particular types of event (e.g. muscle pain) and, if they do, to quantify such effects in different clinical circumstances. 

We also coordinate the work of the Stroke Treatment Trialists’ (STT) Collaboration, which includes ten trials assessing alteplase for the treatment of acute ischaemic stroke. We have reported on the effects of alteplase on functional outcomes, mortality and on the risk of intracerebral haemorrhage, and are now planning to analyse how the effects on such outcomes vary according to the abnormalities documented on the baseline CT scan. 

We are planning to update analyses of the effects of aspirin for the primary prevention of cardiovascular disease within the Antithrombotic Trialists’ (ATT) Collaboration. We expect the results of our 15,000 patient ASCEND trial to become available during 2018, together with several other recently completed large trials of aspirin, so there will be an opportunity to explore the effects of aspirin in a wider range of people at intermediate risk of cardiovascular disease, including those with diabetes mellitus and the elderly.

The Gastroprotectant Trialists (GPT) Collaboration is a large meta-analysis of the effects of gastroprotectants, which combines data from over 1,200 randomised trials including more than 200,000 patients worldwide. We have found that gastroprotectant drugs can more than halve the risk of developing peptic ulcer disease (irrespective of whether NSAIDs, such as ibuprofen or aspirin are also being taken) and more than treble the healing of existing peptic ulcers. In those already experiencing acute upper gastrointestinal bleeding, gastroprotectants reduce the risk of further upper gastrointestinal bleeding by about a third.