Meta ‐analysis of clinical outcomes of PCSK9 modulators in patients with established ASCVD

AbstractThe advent of monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) ushered in a new era of dyslipidemia pharmacotherapy. The first two antibodies targeting PCSK9 (evolocumab, alirocumab) approved by the United States Food and Drug Administration (FDA) provided significant and sustained reductions in atherogenic lipids and a reduced risk of atherosclerotic cardiovascular disease (ASCVD) events. More recently, phase 3 trials of inclisiran —a small interfering RNA-based agent targeting PCSK9—reported similar lipid-lowering effects and preliminary evidence of ASCVD risk reduction, although significant questions remain regarding the extent of benefits across cardiovascular outcomes. We conducted a systematic review and meta-analysis (random-effects model) of the available data on lipid lowering, incidence of atherosclerotic cardiovascular disease (ASCVD) events, and safety of pharmacologic agents targeting PCSK9. A significant and consistent reduction in low-density lipoprotein cholesterol (LDL-C) was observed across all agent s (−51% [95% confidence interval {CI}: −61%, −41%]). Despite the impressive reduction in LDL-C, the individual effects on mortality, cardiovascular death, myocardial infarction (MI), and stroke remained nonsignificant. However, a consistent reduction was observed in the composite outcomes of M I, stroke, and cardiovascular death [relative risk {RR} (95% CI): 0.80 (0.73–0.87)] and MI, stroke, unstable angin...
Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - Category: Drugs & Pharmacology Authors: Tags: TI ON ADVANCES IN CARDIOVASCULAR PHARMACOTHERAPY Source Type: research