Guidelines, Clinical Evidence, and Real-Life Practice: How to Find Your Way in Managing Hypercholesterolaemia

Abstract

Prof Masana presented evidence that low-density lipoprotein (LDL) cholesterol is a causal factor for atherosclerosis and that cardiovascular disease (CVD)-relative risk (RR) is reduced proportionally to LDL reductions, regardless of the type of monotherapy used. Combination therapy offers the advantage of increased lipid-lowering efficacy and a reduction in the side effects associated with high-intensity statins. The rationale thus exists for replacing high-intensity statin therapy with high-intensity cholesterol-lowering therapy. Prof Farnier gave an in-depth description of the results of the IMPROVE-IT, FOURIER, and ODYSSEY-Outcomes trials, demonstrating that the magnitude of clinical benefit is independent of whether it is achieved by statins, ezetimibe, or PCSK9 inhibitors. The IMPROVE-IT study also showed that the magnitude of benefit is proportionate to the absolute decrease in LDL cholesterol. This is consistent with the conclusions of a meta-analysis of randomised controlled statin trials, showing that patients achieving very low LDL cholesterol levels have a reduced risk of major cardiovascular (CV) events compared with those achieving moderately low levels. The greatest benefits for reductions in major adverse CV events from lowering LDL cholesterol occur in patients with diabetes. The above studies have led the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) taskforce on PCSK9 inhibitors to outline a strategy for additional treatment, with patients on maximally-tolerated statin doses failing to achieve LDL cholesterol goals at 4 weeks being considered for ezetimibe treatment, and those failing to achieve goals after a further 4 weeks being considered for PCSK9 inhibitors. Votes from the audience, collected at the start and end of each presentation, showed that the speakers convinced delegates that the lower the LDL cholesterol level achieved the better the outcome for patients would be, that combination therapy is as effective as single dose high-intensity statins, and that statins plus ezetimibe should be considered as standard treatment in high-risk patients, particularly in Type II diabetes mellitus (T2DM) patients.