Underutilization of combination therapy in lipid lowering: a missed opportunity

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality worldwide. LDL cholesterol (LDL-C) is the key driving force in the atherosclerotic process, and LDL-C lowering can change the trajectory of ASCVD and decrease cardiovascular (CV) events. In the light of new evidence, LDL-C goals have become more stringent in the ESC guidelines, especially for high-risk patients.1 Unfortunately, these goals are rarely reached in real life as shown in registries such as EUROASPIRE documenting a large implementation gap.2 The reasons for underimplementation are multiple, but underutilization of therapies is a major cause. Statins are the first line of treatment in lipid-lowering therapy (LLT) but may not get the patient to the guideline-recommended goals, and combination therapy may be necessary. The recent ESC guidelines recommend adding ezetimibe first, followed by proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody inhibitors to the treatment regimen, since both agents have been documented to decrease CV events further on top of a statin.3 However, combination therapy with non-statin drugs is widely underutilized. A recent pan-European observational study (the DA VINCI study) reported that a majority of patients under both primary and secondary prevention were receiving moderate-intensity statin therapy. Only 28% were receiving high-intensity statins, 9% ezetimibe combination therapy, and 1% PCSK9 inhibitors.4 As a result, only a third of the patients achieved their LDL-C goal as recommended in the recent guidelines.