Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors: comparing and contrasting guidance across the Atlantic

This editorial refers to ‘European Society of Cardiology/European Atherosclerosis Society Task Force consensus statement on proprotein convertase subtilisin/kexin type 9 inhibitors: practical guidance for use in patients at very high cardiovascular risk’, by U. Landmesser et al. , doi:10.1093/eurheartj/ehw480. The approval of two proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, evolocumab and alirocumab, in both Europe and the USA has provided clinicians with a powerful new tool in their armamentarium that, on top of high-intensity statin therapy, can lower LDL-cholesterol (LDL-C) approximately another 60%.1 The question now is for which of our patients should it be used? In the USA, the 2013 ACC/AHA Cholesterol Guidelines largely focused on defining populations who should receive high-intensity statin therapy.2 In a departure from previous guidelines, the Expert Panel felt there was no evidence to support titrating cholesterol-lowering therapy to achieve specific LDL-C levels. The guidelines did note that one could consider adding a non-statin to a statin in an individual who had less than the anticipated therapeutic response (i.e. <50% reduction in LDL-C when treated with a high-intensity statin), but noted that the percentage reduction in LDL-C was not in itself a treatment goal. Since those guidelines, the IMPROVE-IT trial has shown that adding ezetimibe to a post-acute coronary syndrome (ACS) population with well-controlled LDL-C on a statin lowered LDL-C from 70 to 54 mg/dL and reduced major adverse cardiovascular events to a degree entirely consistent with what would have been expected from the same LDL-C reduction with a statin.3 Moreover, pooled exploratory data from the Phase II and Phase III studies of PCSK9 inhibitors showed significant reductions in cardiovascular outcomes. …