How do arrhythmias and conduction disturbances contribute to death or rehospitalisation in patients discharged following an admission with acute heart failure? A prospective, observational, multi-centre cohort-study
Dr Roy Gardner, University of Glasgow
£429,737 over 4 years, 6 months
Arrhythmias are likely to have a major role in death and readmission to hospital in patients with heart failure (HF), but this issue has not been systematically studied. This prospective, observational, multi-centre cohort study will examine the role of arrhythmias in HF by undertaking continuous, long-term surveillance for arrhythmias using injectable cardiac monitors (ICMs). Patients will receive an ICM during an index admission for HF, and will be followed up for ≥2 years. The main analysis will be the association of arrhythmias with rehospitalisation and death (causes will be adjudicated). In patients who die, ICMs also record the terminal electrical rhythm. The identification of sudden deaths involving ICM-documented arrhythmic mechanisms will form a novel endpoint. Additional sub-studies (for willing patients) will include (i) cardiac MRI (ii) comprehensive characterisation of cause of death in HF using ICM arrhythmic data and post-mortem examinations (to identify non-arrhythmic causes). This study may identify new targets for intervention in HF, and inform the design of randomised trials of pharmacological and device-based therapies.
Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST)
Professor Thompson Robinson, University of Leicester
£323,014 over 3 years
Although thrombolytic therapy with alteplase given within 4.5 hours of ischaemic stroke onset improves clinical outcome, patients who have new symptoms on waking (wake-up stroke) are excluded; about 1 in 5 strokes present in this way. Tenecteplase has potential advantages over alteplase: greater fibrin specificity, rapid action, longer half-life, single bolus administration and promising clinical trial results compared with alteplase. TWIST is an international, multi-centre, randomised, open-label, blinded endpoint trial of tenecteplase for acute ischaemic wake-up stroke. In total, 500 patients eligible for treatment within 4.5 hours of waking with symptoms will be randomly allocated to 0.25mg/kg bolus dose of tenecteplase (maximum 25mg) in addition to standard care versus standard care. Follow-up will be undertaken at days 2 and 7 (or discharge if earlier), with the primary functional outcome (modified Rankin scale) assessed at 3 months. Other secondary efficacy, safety and health economic outcomes will be measured at 7 days and 3 months, and collected through record linkage with national registries up to 3 years after admission. A total of 500 patients will be recruited.
OPTIMAS: OPtimal TIMing of Anticoagulation after AF-associated acute ischaemic Stroke: a randomised controlled trial
Professor David Werring, University College London
£2,045,998 over 5 years
Oral anticoagulation is highly effective for long term stroke prevention in people with atrial fibrillation (AF) but the safety and net benefit in acute AF-related stroke have not been established. Early anticoagulation (i.e. in the first few days) could prevent stroke recurrence but might increase the risk of symptomatic intracranial haemorrhage, including haemorrhagic transformation of the infarct. OPTIMAS will randomise 3,474 patients with AF-related acute ischaemic stroke to early (≤4 days after a stroke) or later anticoagulation (5-14 days after a stroke) using direct oral anticoagulants (DOACs) to find out the optimal timing of anticoagulation after acute AF-related ischaemic stroke. The primary outcome will be a 90-day composite of recurrent ischaemic stroke, intracranial haemorrhage, systemic embolism, and death.
Troponin in Acute chest pain to Risk stratify and Guide EffecTive use of Computed Tomography Coronary Angiography (TARGET-CTCA)
Professor Nicholas Mills, University of Edinburgh
£1,115,723 over 5 years
Most patients presenting to hospital in the United Kingdom with symptoms suggestive of acute coronary syndrome will be discharged home without further investigation or treatment once myocardial infarction has been ruled out. A significant proportion of these patients will have unrecognised or important coronary artery disease (CAD), but the appropriate subsequent management of these patients is unclear and varies widely in practice. High-sensitivity cardiac troponin concentrations below the threshold used to diagnose myocardial infarction are increasingly recognised as a powerful predictor of the future risk of major adverse cardiovascular events. We hypothesise that, once myocardial infarction has been excluded, patients with acute chest pain and high-sensitivity cardiac troponin concentrations ≥5 ng/L will benefit from computed tomography coronary angiography to diagnose underlying CAD and direct subsequent management that will improve clinical outcomes. We will evaluate this in a multi-centre randomised controlled trial of patients presenting to the emergency department with acute chest pain.
Start or STop Anticoagulants Randomised Trial (SoSTART) for atrial fibrillation after intracranial haemorrhage: safety phase
Professor Rustam Al-Shahi Salman, University of Edinburgh
£721,223 over 3 years
Atrial fibrillation (AF) becomes more prevalent with age and confers a high risk of systemic embolism (mostly to the brain), especially in older adults with other vascular risk factors. Randomised controlled trials (RCTs) have shown that oral anticoagulant drugs are highly effective for preventing systemic embolism in people with AF. However, RCTs of oral anticoagulation for AF excluded people with intracranial haemorrhage (ICH), leaving uncertainty about the risks and benefits in this group. The SoSTART study will investigate whether starting oral anticoagulants after ICH in people with atrial fibrillation results in a beneficial net reduction of all serious vascular events compared with not starting anticoagulants. This funding covers the safety phase of SoSTART, which will randomise at least 190 participants with AF after ICH and follow them for the occurrence of all serious vascular events over at least one year; this will provide 90% power to test whether starting oral anticoagulation compared with avoiding oral anticoagulation does not increase the primary outcome of recurrent ICH from 6%/year to ≥18%/year at 1-sided p=0.025 (non-inferiority). If starting oral anticoagulation is sufficiently safe, we would proceed to a main phase to investigate net benefit.