Reducing Residual Risk in Secondary Prevention of Cardiovascular Disease

Prevention of cardiovascular disease (CVD) spans the human lifespan, including primordial, primary, and secondary prevention efforts. Extensive evidence from epidemiological, genetic, and animal studies confirms the central importance of elevated low-density lipoprotein (LDL) cholesterol (LDL-C) in atherosclerotic CVD events.1 The Cholesterol Treatment Trialists Collaboration provides per-person documentation from large-scale randomized clinical trials of the striking reduction in CVD events per 1 mmol (38.8 mg/dL) of LDL-C lowering with statins over a wide range of baseline LDL-C values.2,3 It is worth recalling that the major statin trials were not designed to determine the effectiveness of titration to LDL-C or even to non–high-density lipoprotein cholesterol goals by statins but were fixed-dose comparisons of various statins against placebo and then, more recently, large-dose statin therapy versus moderate-dose statin therapy. What is not so clear is whether we can intervene to reduce so-called residual risk further in secondary prevention patients optimally treated with statin therapy. A promising short list of proposed potential targets other than LDL includes efforts to promote smoking cessation and therapies to improve the prothrombotic and inflammatory state of the metabolic syndrome and to control elevated blood pressure.4Article see p 1979The article by Mora et al5 in this issue of Circulation is helpful in shedding light on this unresolved but important clinical problem. The investigators used data from a large-scale clinical trial of secondary prevention patients called Treating to New Targets (TNT). They evaluated risk factors for recurrent CVD events in those treated with intensive statin therapy (atorvastatin 80 mg/d) to address the challenges inherent in further risk reduction for those who had major cardiovascular events despite high-dose (atorvastatin 80 mg/d) statin therapy.The trial design of TNT included enrollment of participants with chronic coronary artery …