title: Lipids, Lipoproteins, and Cardiovascular Disease: Clinical Pharmacology Now and in the Future.
abstract: BACKGROUND
  While substantial benefit has accrued with respect to prevention and treatment of atherosclerotic cardiovascular disease (ASCVD) since the advent of statin therapy, much remains unknown and there is considerable need to address residual risk beyond statins. Moreover, many individuals are unable to tolerate statins.
  
  
  METHODS
  As a result of several recent clinical trials and publications describing early Phase 1-3 clinical trials, the authors briefly discuss the current situation regarding pharmacological management for the prevention and treatment of individuals with disorders of lipid and lipoprotein metabolism, outline some of the unanswered questions, and speculate on where we might expect to be in 5-10 years.
  
  
  RESULTS
  Fortunately, recent developments in drug therapy hold considerable promise of additional benefits. In addition, new drugs in the pipeline, ongoing clinical trials, and new approaches to treatment hold promise for further improvements in therapy in the foreseeable future. During the next 5-10 years, we expect to know whether the PCSK9 inhibitors indeed live up to their promise and result in the hoped-for reduction in ASCVD events, whether triglyceride lowering indeed adds additional benefit, how best to approach HDL, and the importance of lipoprotein (a). Advances in the use of molecular biological approaches such as anti-sense oligonucleotides and RNA silencing, and the use of biological agents such as PSCK9 antibodies, is likely to play an important role in these advances.
  
  
  CONCLUSIONS
  The advent of PCSK9 inhibitors is likely to provide a major breakthrough in the management of individuals with heterozygous familial hypercholesterolemia, patients with established ASCVD who are unable to reach targets with other therapies, and high-risk individuals with statin intolerance. The next 5-10 years should also clarify uncertainties concerning the pharmacological management of individuals with low levels of HDL-cholesterol, hypertriglyceridemia, and elevated lipoprotein (a).
authors.affiliation: University of Washington Diabetes Institute, Seattle, Washington 98195 (A.C.) and University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado 80045 (R.H.E.).
authors.forename: Alan
authors.initials: A
authors.lastname: Chait
authors.affiliation: University of Washington Diabetes Institute, Seattle, Washington 98195 (A.C.) and University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado 80045 (R.H.E.).
authors.forename: Robert H
authors.initials: RH
authors.lastname: Eckel
mesh_terms: D001275:ATP Citrate (pro-S)-Lyase / Q000037:antagonists & inhibitors; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D008076:Cholesterol, HDL / Q000097:blood; D002986:Clinical Trials as Topic; D015316:Genetic Therapy; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000502:physiology*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D014280:Triglycerides / Q000502:physiology
chemical_list: D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D008074:Lipoproteins; D014280:Triglycerides; D001275:ATP Citrate (pro-S)-Lyase; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases