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October 2017

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Therapy—Breakthrough in Low-Density Lipoprotein Cholesterol Lowering, Breakdown in Value

Author Affiliations
  • 1Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
  • 2Yale University School of Medicine, New Haven, Connecticut
  • 3Stanford University School of Medicine, Stanford, California
JAMA Cardiol. 2017;2(10):1066-1068. doi:10.1001/jamacardio.2017.2911

In the 30 years since the approval of lovastatin by the US Food and Drug Administration in 1987, cardiovascular medicine has pushed the limits of prevention of atherosclerotic cardiovascular disease through lowering of low-density lipoprotein (LDL) cholesterol. Early pivotal trials showed unequivocally that use of statins prevented heart attacks and strokes and saved lives. More potent statins were more effective in lowering LDL cholesterol and reducing mortality, with benefits in rough proportion to the mean achieved reduction in LDL and few serious adverse effects. However, over the last decade, progress in reducing morbidity and mortality from atherosclerotic cardiovascular disease with statins has slowed owing to 3 factors: (1) insufficient LDL cholesterol lowering in some patients, despite high-intensity statins; (2) intolerance to statins, leading to dose reduction or discontinuation; and (3) nonadherence.