ESC 2012 Report – Cholesterol and risk: past, present and future – The benefits of adding newer cholesterol-lowering agents to the statins

by Zara Qadir – ESC Geoffrey Rose Lecture on Population Sciences.   The recipient of the ‘ESC Geoffrey Rose Lecture on Population Sciences’ went to Rory Collins (pictured), who is British Heart Foundation Professor of Medicine and Epidemiology, at the University of Oxford. Rory Collins received the first knighthood in fifty years in the field of cardiology for his work in establishing large-scale epidemiological studies examining the causes, prevention and treatment of cardiovascular disease. He has also been closely involved in developing approaches to the combination of results from related studies (“meta-analyses”). Cholesterol and risk was the subject of Collins’s Named Lecture, which considered cholesterol and risk from a past, present and future perspective.The first confirmed association between CHD incidence and cholesterol link was made in 1980 by Ancel Keys who studied the influence of diet on health. But it was 10 years ago that the Heart Protection Study[1] first showed unequivocally that statins could produce substantial benefit in a much wider range of subjects than had ever been contemplated. Those findings were then confirmed by meta-analysis of the many different trials of statins, and most recently in a review[2] performed by Collins’s own group at the Clinical Trial Service Unit (CTSU) of Oxford University, collectively known as the Cholesterol Treatment Trialists collaboration. This study, which included 27 randomised trials (n=170,000), showed that, even in healthy people, reducing blood levels of LDL-cholesterol cut the risk of coronary events and ischaemic stroke by around one-third. Healthy people given a statin also had lower overall mortality rates than those given placebo. This was seen across all populations (those with CHD, those non-CHD, diabetes, sex, age and BMI).  “The meta-analysis shows that as treatment continues, the absolute benefit gets bigger and bigger, and there is no evidence that continued treatment long term benefits,” said Professor Collins. Collins also provided some background to trials examining the benefits of adding newer cholesterol-lowering agents such as Ezetimibe to the statins.

Collins in his lecture also explored the balance between benefits versus the risks. In the CTT analysis, there was no emerging cancer excess with prolonged follow-up. In the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial (n= 5,804), no difference was reported in cognitive function was seen between treatment groups[3].  Professor Collins remarked that if you know that treatment is known to be effective, you need a higher threshold for safety concerns (of similar strength to evidence that is typically required for efficacy). “It is important to get the absolute benefits and risks in context,” said Collins.

Professor Collin’s take home message: Each 1mmol/L LDL-C reduction reduces the annual rate of vascular events by about one-fifth. Larger LDL-C reductions safety produces definite larger reductions in the incidence of heart attacks, revascularisations and ischaemic strokes. Similar proportional reductions in all of the subgroups studied (including renal disease and primary prevention). No threshold within the cholesterol range studied, which implies that reducing LDL-C by 2-3 mmol/L would reduce vascular event by about 40-50%. However, the benefits of raising HDL-C remain to be demonstrated.