Intensive LDL lowering therapy for prevention of recurrent cardiovascular events: a word of caution

Physicians visiting the European Society of Cardiology (ESC) congress in London could not miss the extensive marketing of new low-density lipoprotein (LDL)-lowering therapies with ezetimibe and the PCSK-9 inhibitors. However, we think and will argue that a word of caution on their use in clinical practice is appropriate. The European guidelines on cardiovascular disease prevention and management of stable coronary artery disease recommend a spectrum of measures to limit the risk of a first or recurrent coronary event, including abstinence from smoking, balanced nutrition, moderate exercise as well as drugs to control blood pressure, lipids and glucose levels.1,2 Specific targets are mentioned for blood pressure (130–139/80–85 mmHg) and LDL-cholesterol (1.8–3.0 mmol/L). However, these targets for LDL-cholesterol—based on the observations that lower LDL levels are associated with ever-lower risk for cardiovascular events—are quite arbitrary. In clinical practice, these targets are often not reached, in spite of intensive medical therapy.3,4 For instance, in the EUROASPIRE-IV survey, 64% of males and 78% of females had LDL levels higher than 2.0 mmol/L.3 Furthermore, 18% of these patients continued smoking after an acute coronary event or revascularization procedure, while 42% had an elevated blood pressure. The usefulness of specific targets for LDL cholesterol levels has been questioned and has been abandoned in recent American guidelines.5 Nevertheless, European opinion leaders continue to emphasize the value of targets to improve adherence to therapy and to consider additional therapy, such as combination of statin and ezetimibe, in a small group of very high-risk patients .6 Such targeting is supported by the recently published results of IMPROVE-IT7 as will be discussed below. Furthermore, we …