ProfessorKosh Ray

Current Programme of Research

Familial Hypercholesterolaemia (FH) is the most common autosomal dominant disorder affecting man (1:300) and is underdiagnosed and undertreated with catastrophic consequences for those affected. To provide data on how FH is diagnosed and treated and to ascertain the consequences of current clinical practice, I have established a global registry of FH (FH Studies collaboration) which has attracted four grants. This registry is led by my group and endorsed by the European Atherosclerosis Society and extends across Europe, Africa, South America and the Asia Pacific region. This includes 80 countries and 80 000 cases

Partnering with several Pharmaceutical Companies the Imperial Clinical Trials Unit-Global seeks to bring more clinical trials to the UK and led by the UK. This is an extension of my current role as National Lead Investigator and Steering Committee Member on many global trials, streamlining screening, recruitment and management reducing costs of running trials in the UK.

Impact of Research to Date

I led the global devlopment programme for inclisiran, and was part of the leadership of trials of bemepdoic acid, alirocumab and obicetrapib all of which made it to the clinic worldwide.

Our work on FH led to EU level endorsement of Childhood screening for FH in the Prague Declaration. 

Registries led include Santorini and Da Vinci which showed the unmet need in choleterol managment in Europe and the path forward with combination therapies. 

 
The work conducted so far on statins has informed several international guidelines for heart disease, which are cited as proving evidence for specific approaches to patient care. For instance the demonstration of the early benefits of intensive statin therapy over standard therapy within 30 days of an ACS event is the best guidance anywhere for this approach in clinical practice (ESC guidelines). The demonstration that older patients derive greater absolute benefit from intensive lipid lowering and that this can be done safely after an ACS should ensure that these often neglected individuals who do not receive evidence based care are appropriately treated (ACC/AHA guidelines for treatment of the elderly patient with MI).

Our work on more vs less intensive glycaemic control shows that more intensive therapy reduces coronary heart disease (CHD) events without an excess risk of death, thus reassuring clinicians and guidelines committees. We have also demonstrated that triglycerides are unlikely to be causal for CHD risk and screening can be simplified by using non-HDL-C and HDL-C informing EAS/ESC guidelines. Studies of dysglycaemia have demonstrated that the risk of cardiovascular disease (CVD) from dysglycaemia is modest with a non-linear relationship between risk and CVD.

Our work on statins has shown a dose dependent increase in the risk of diabetes which have led to FDA and EMEA label changes for statins. Our work on aspirin in primary prevention has shown that aspirin does not reduce cardiovascular death and the benefits on non-fatal MI are offset by a significant increase in bleeding. This has lead many guidelines to discontinue routine aspirin use in primary prevention.

Public Engagement

As President of the EAS and now Immediate Past President I engage with researchers public and societies teaching raising awareness of CVD and fostering engament.

Much of my work has attracted high profile attention in the lay press. I therefore have frequently engaged with media over the last 6 years to disseminate key research messages in a simple format for the general public. Furthermore, I frequently represent the British Cardiovascular Society in many of these engagements to contextualise new and often controversial research findings on prevention.

In my role as the lead for the European Atherosclerosis Society Familial Hypercholesterolaemia (FH) Studies Collaboration, I am working with patient representative organisations/charities like HEART UK, The FH Foundation and the International FH Foundation to help disseminate awareness of FH and lobby for changes in screening and how this condition is managed.

CURRENT RESEARCH GRANTS
Amgen Investigator Initiated Grant (PI) A cross-sectional study of the management of high risk patients in Europe

European Atherosclerosis Society (EAS) with Sanofi, Amgen, and MSD Investigator Initiated Grants (PI) To establish the EAS endorsed Familial Hypercholesterolaemia (FH) Studies Collaboration

Pfizer Independent Grants for Learning and Change (PI) To establish a risk prediction tool for additional lipid lowering therapies

Pfizer Global Grants for Dyslipidemia (PI) To establish a global collaborative registry of Familial Hypercholesterolaemia (FH)

Sanofi Research Grant (PI) Statin Intolerance analyses from CPRD

Sanofi Research Grant (PI) To collect NHS Vascular Health Checks in South London to establish a contemporary cohort of 200 000 participants. The TOGETHER study.

CLINICAL TRIALS
SONAR (Events Adjudication Committee Member, Sponsored by Abbvie) An RCT of a novel endothelin inhibitor atrasentan on CV death or end stage renal disease.

Declare TIMI 58 (National Lead Investigator, Sponsored by AstraZeneca) Multi-centre study to test if dapagliflozin when added to a patients current anti-diabetes therapy is effective in reducing cardiovascular events such as myocardial infarction (MI) (heart attack), ischemic stroke, and cardiovascular (CV) related death, compared with placebo. Enrolment of 18,000 subjects anticipated with completion expected in 2019.

STRENGTH (National Lead Investigator and Executive Committee Member, Sponsored by AstraZeneca) Phase 3 RCT of Omega 3 Fatty acids for the secondary Prevention of CVD.

THEMIS: Phase 3 RCT (National Lead Investigator and Steering Committee Member, Sponsored by AstraZeneca) Assessing the effect of Ticagrelor in stable CHD. Global study of 17,000 patients. Expected completion 2017.

CARAT (Executive Committee Member, Sponsored by Cerenis) Phase 3 RCT assessing the efficacy of a HDL mimetic on atheroma burden on IVUS.

CAMELLIA TIMI 61 (Steering Committee Member, Sponsored by Eisai) Phase 3 trial of a novel agent for weight loss improvement of metabolic traits and CVD outcomes.

CLEAR CVOT (Executive Committee Member, Sponsored by Esperion) Phase 3 RCT assessing the efficacy of ETC1002 on CVD outcomes in patients at CVD risk intolerant of statins.

HARMONY Esperion Lipid lowering trials (Executive Committee Member, Sponsored by Esperion) Phase 3 RCT assessing the efficacy of ETC1002 on LDL-C.

PROMINENT (Steering Committee Member, Sponsored by Kowa) Phase 3 RCT assessing the efficacy of K877on CVD in people with DM and high TG low HDL-C. Commencing 2017.

ACCENTUATE (Executive Committee Member, Sponsored by Lilly) Phase 3 trial of Anacetrapib on Lipid levels among those with FH or dyslipidemia intolerant of current therapies.

Lilly Phase 3 Lipid Lowering programme of a novel PCSK9 Mab. Chair of Statin Intolerance Study (Executive Committee Member, Sponsored by Lilly) Phase 3 RCT assessing the efficacy of Mab to PCSK9 on LDL-C. Commencing 2017.

ORION 1 (PI and Co-Chair of the Executive Committee, Sponsored by Medicines Company) Phase 2 RCT assessing the efficacy of a novel intervention with iRNA therapy to PCSK9 on lipids.

BETONMACE (Chair of International Executive Committee, Sponsored by Resverlogix) Phase 3 RCT assessing the efficacy of BET inhibition on CVD.

Odyssey Outcomes (National Lead Investigator, Sponsored by Sanofi Regeneron) Multi-centre study to compare the effect of alirocumab SAR236553 (REGN727) with placebo on the occurrence of cardiovascular events in patients who have experienced an acute coronary syndrome (ACS).

Odyssey Diabetes 1 (Executive Committee Member, Sponsored by Sanofi Regeneron) Phase 3 RCT assessing the efficacy of Alirocumab on lipids in patients with atherogenic dyslipidaemia and DM.

Odyssey Diabetes 2 (Executive Committee Member, Sponsored by Sanofi Regeneron) Phase 3 RCT assessing the efficacy of Alirocumab on lipids in patients with DM treated with insulin.