Introduction

Drug therapies targeted at the reduction of low-density lipoproteincholesterol (LDL-C) are mainstream in the treatment of cardiovascular disease (CVD) and particularly for the prevention of coronary heart disease. In patients who do not have a sufficient response to, or who do not tolerate traditional LDL-C-lowering therapies such as statins or ezetimibe, monoclonal antibodies (mAbs) against PCSK9 (PCSK9 inhibitors) may provide an alternative treatment. Non-mAb-based PCSK9 inhibitors such as inclisiran are also emerging but currently lack robust outcome data1 and their effects are not considered in the current review. In this synopsis, we summarise findings from a recent update of a Cochrane systematic review on the efficacy and safety of PCSK9 inhibitors.2 This article focuses on the effects on outcomes (CVD and total mortality), safety, and the quality of the evidence in studies of mAb PCSK9 inhibitors alirocumab and evolocumab. Most of the available studies compared PCSK9 mAb treatment against placebo (against a background of usual care including statin and or ezetimibe), with a smaller group of studies evaluating the effects of PCSK9 mAb directly against statins and/or ezetimibe (none of the trials compared PCSK9 exclusively against statin treatment).