Looking Beyond Statins: Will the Dollars Make Sense?

Abstract

Article, see p 1931 > “It is always wise to look ahead, but difficult to look further than you can see.” > > —Winston Churchill The noteworthy article by Ray et al1 in this issue of Circulation provides a tantalizing glimpse into the future. It points to the potential of 2 nonstatins—alirocumab, a proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor, and ezetemibe—to reduce atherogenic lipoproteins with proportional reductions in major adverse cardiovascular events beyond that achieved with statins alone. The authors make an important observation: a continuous relationship exists between average on-treatment low-density lipoprotein cholesterol (LDL-C) and major adverse cardiovascular events. Moreover, they found no observed effect attenuation at low achieved levels of LDL-C <50 mg/dL. But their analysis is not conclusive. As the authors note, there are significant limitations due to a low number of events, the short trial duration (≤2 years), and, importantly, the post hoc nature of the analysis. On the other hand, if results from prospective outcome trials are in accord with these preliminary data, it will be appropriate to update current cholesterol guidelines. It is helpful to review what current guidelines stated. The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) Cholesterol Guidelines (2013 GL) endorsed lifestyle as the foundation for atherosclerotic cardiovascular disease (ASCVD) prevention.2 The guideline panel proposed 3 critical questions to determine when and how pharmacologic treatment should be implemented. These critical questions generated a comprehensive search for high-quality randomized clinical trials (RCTs) or meta-analyses of these RCTs by an outside contractor chosen by the National Heart Lung Blood Institute. Low-quality studies were not allowed to contribute to the evidence. The panel then published their final recommendations under the auspices of the ACC and AHA. Other guidelines that adhered closely to the RCT evidence include the National Institutes of Clinical Excellence guidelines3 …