Improving cardiovascular outcomes by intensifying low density lipoprotein lowering therapy in high-risk patients

This editorial refers to ‘The benefit of adding ezetimibe to statin therapy in patients with prior coronary artery bypass graft surgery and acute coronary syndrome in the IMPROVE-IT trial’, by A. Eisen et al. , doi:10.1093/eurheartj/ehw377. One of the foundations of preventive cardiology is that the higher risk an individual person is for future cardiovascular events, the more aggressively that individual should be treated to reduce risk. While different medical societies throughout the world have recommended different approaches to assess risk, this premise has been universally accepted and is factored into all guidelines. Reduction in low density lipoprotein cholesterol (LDL-C) is a cornerstone of cardiovascular risk reduction, but questions remain about how aggressively LDL-C should be reduced in high-risk patients. A meta-analysis of statin trials by the Cholesterol Treatment Trialists (CTT) demonstrated every 1.0 mmol/L reduction in LDL-C is associated with a corresponding 20–25% reduction in cardiovascular events over 5 years.1 Based on these abundant data, statins are widely used to reduce risk in high-risk individuals. In contrast, the use of non-statin cholesterol lowering agents in addition to statins to reduce cardiovascular risk has been controversial. Prior to 2015, there were no large randomized trials to assess the benefits of adding a non-statin agent to statin therapy in reducing CV events. The 2013 American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults focused on statin therapy as the primary goal,2 while the 2014 National Lipid Association recommendations for patient-centred management of dyslipidaemia used LDL-C goals with non-statin agents as necessary to achieve them.3 The IMPROVE-IT trial published in 2015 was the first large scale randomized trial to show the benefit of a non-statin agent in reducing cardiovascular events when added to statin therapy.4 The benefits …