Individual patient meta-analyses of randomized trials of antithrombotic treatments in cardiovascular disease
The Antithrombotic Treatment Trialists’ (ATT) Collaboration was established over 20 years ago in order to provide analyses of the effects of antithrombotic therapy on vascular events in various populations, resulting in major publications on the effects of antiplatelet regimens in high-risk patients (BMJ 1994 and 2002), and aspirin for low-risk individuals (Lancet 2009).
Since 2002, when antiplatelet therapy was last surveyed by the ATT, several hundred additional trials have examined antiplatelet regimens. These include trials of dual antiplatelet therapy (DAPT), eg aspirin plus a P2Y12-inhibitor such as clopidogrel, particularly in the context of acute coronary syndromes (ACS). Although DAPT results in net benefit for many high risk patients, many clinical questions remain unanswered, including: the optimal timing for commencing DAPT in ACS, the optimal duration of DAPT after the index event, and the choice of antiplatelet regimen among patients receiving oral anticoagulation for atrial fibrillation.
In some conditions, chiefly those in which embolism is the main cardiovascular complication, vitamin K antagonists have been shown to be more effective than antiplatelet therapy. More recently, new oral anticoagulants (NOACs) have been developed, including agents acting against the coagulation enzymes thrombin (dabigatran) or factor Xa (eg rivaroxaban), and a number of randomised trials have assessed their effectiveness in a wide range of high-risk conditions. These trials have shown that the newer anticoagulants have potential advantages over warfarin, including a lower risk of intracranial bleeding, but it remains unclear which types of patients derive greatest benefit.
There is a need, therefore, for meta-analyses of individual patient data from the many trials of newer antithrombotic regimens in order to inform clinical management. The ATT Collaboration now plans to set up an infrastructure to allow such analyses to be conducted.
Research Experience, Research Methods and Training
- Helping to establish a collaboration of trialists engaged in large-scale trials of antithrombotic regimens
- Planning and drafting statistical analysis plans to examine the incremental effects of particular antithrombotic drugs in different treatment comparisons, using a ‘network meta-analysis’ approach, for both tabular and individual patient data.
- Conducting and interpreting the findings of meta-analyses, and planning exploratory analyses based on preliminary findings.
Field Work, Secondments, Industry Placements and Training
Students will learn to identify trials, develop collaboration with trialists, review and appraise clinical trials, develop statistical analysis plans, conduct and interpret meta-analytical analyses and draft manuscripts.
A clinically qualified doctor, or graduate in a related subject, with highly developed numeracy skills and an interest in the field of cardiovascular medicine.