Cardiovascular studies

Duration of Dual Anti-Platelet Therapy in Acute Coronary Syndrome

We hope this study will show the best way of treating patients after a heart attack. Coronary heart disease causes the most deaths worldwide and happens when small fatty lumps (plaques) build up, narrowing the blood vessels supplying the heart. If the plaques become disrupted a small blood clot can form reducing the flow of blood and oxygen to part of the heart muscle - and this sometimes leads to a heart attack or chest
pains (acute coronary syndrome).

The standard treatment after an acute coronary syndrome is to give two blood thinning drugs. This dual anti-platelet therapy helps the fatty lumps heal in order to stop the heart attacks happening again - but thinning the blood can also raise the risk of bleeding. Several trials have shown that taking dual anti-platelet therapy does help stop heart attacks,
but it’s not clear how long dual anti-platelet therapy should last to maximise this benefit but minimise the risk of serious bleeding. Recent evidence suggests that giving dual anti-platelet therapy for a shorter time is better because the risk of serious bleeding, or even death, is higher the longer it is given. We want to test long and short durations of dual anti-platelet therapy in a UK and International trial of 18,318 heart attack
patients to settle this unanswered clinical question once and for all. Patients will be recruited from hospital wards and those who decide to take part will get (at random) dual anti-platelet therapy for either 3 months or 12 months. Patients do not need to do anything else for the study but we’ll look at their health records so we can collect data about their health to see which works best. Patients have been involved in the development of this study and will be involved in looking at progress of the study.

The Use of Blood Biomarkers, Including Extracellular Vesicles, to Improve the Diagnostic Accuracy of Cardiac Assessment by Stress Echocardiogram

Stress echocardiogram involves ultrasound of the heart during cardiac stress, to identify patients who may have coronary artery disease. It is a noninvasive method for assessing the heart and is used as screening test in high risk individuals to identify those who should go forward for more invasive procedures, such as angiogram. However, stress echocardiogram is not 100% accurate in detecting coronary artery disease, resulting in some patients undergoing unnecessary procedures and others not being picked up.

We aim to investigate the use of markers in the blood to improve the diagnostic accuracy of stress echocardiogram. Specifically we are interested in measuring extracellular vesicles, which are blebs of cell membrane released from blood cells during cell activation and death.
The findings from our pilot study suggest that monitoring levels of extracellular vesicles during a stress echocardiogram procedure can improve the predictive value of this test in determining patients who have coronary artery disease. In our pilot study we had limited numbers of participants who had a confirmed diagnosis by angiogram.
This study will increase those numbers and provide an opportunity to determine the role of blood markers during stress echocardiogram.
This study will take place at the Cardiovascular Clinical Research Facility at the John Radcliffe Hospital. It will last three years. Participants will undergo a stress echocardiogram as part of their routine clinical management.

Study of the Impact of Evolocumab on Major Cardiovascular Events

Full title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Impact of Evolocumab on Major Cardiovascular Events in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke

Summary: Elevated cholesterol, in particular low-density lipoprotein cholesterol (LDL-C), can lead to obstructing fatty deposits in blood vessels that can greatly increase the risk of developing cardiovascular disease and experiencing a cardiovascular event.

The purpose of this global study is to assess whether additional lowering of LDL-C with evolocumab can reduce the risk of major cardiovascular events (i.e., heart attack or stroke) in patients at high cardiovascular risk, when evolocumab is taken in addition to the current lipid lowering medical treatment (i.e., statins) for elevated blood cholesterol levels.

To be eligible, patients should be at high cardiovascular risk for experiencing a major cardiovascular event but without previous heart attack or stroke and must be on stable, optimal lipid-lowering background therapy, as per local guidelines for at least 4 weeks.

Eligible participants will be randomised with an allocation ratio of 1:1 to either receive evolocumab or placebo. Randomised means that participants are put into a group by chance. Through the duration of the study participants will receive bi-weekly treatment with evolocumab or placebo in addition to their current lipid lowering therapy medication. It is estimated that enrolment of participants into this study will take approximately 1 year. Participants will be in this study for a minimum of 4 years or up to about 5 years.

The study will be conducted across numerous hospitals and GP practices across the country as well as in most European countries, Asia, South America and North America.

Closed to recruitment - patients in follow up.

HPS-4/TIMI 65/ORION-4: A double-blind randomized placebo-controlled trial assessing the effects of inclisiran on clinical outcomes among people with atherosclerotic cardiovascular disease

Summary:
Previous trials have shown that lowering bad (LDL) cholesterol with statins reduces the risk of heart attacks and strokes. However, among individuals with a previous history of vascular disease, the risk of a further vascular event remains high, even after several years of statin treatment.

Inclisiran is an investigational drug given by subcutaneous (under the skin) injection which lowers bad (LDL) cholesterol. This study aims to find out whether inclisiran, given every 6 months for about 5 years, safely reduces the risk of heart attacks, strokes or the need for urgent coronary angioplasty or bypass grafts, in people who already have known vascular disease.

People are eligible to join the study if they are aged 55 years or older and have known vascular disease (that is they have had a heart attack, stroke or leg artery bypass or angioplasty, or aortic aneurysm repair).
The study will involve 15,000 participants (12,000 in the UK and 3000 in the US). Half of the participants will receive inclisiran injections and half will receive inactive dummy injections (placebo). Which treatment each participant receives will be decided by randomization (like tossing coin). Neither the participants, nor the study staff will know which treatment they are receiving (but this can be found out if needed). Participants will continue their usual medication prescribed by their GP or other doctors.

ORION-4 study clinics will be set up by NHS and academic institutions and will be run by trained research staff. Participants will attend the study clinic four times in the first nine months and then once every six months. At each clinic visit they will be asked questions about their health, will have a blood sample taken and will be given an injection of inclisiran or placebo.