title: Statins in Familial Hypercholesterolemia: Consequences for Coronary Artery Disease and All-Cause Mortality.
abstract: A statin-induced reduction of coronary artery disease (CAD) events and mortality has not been adequately quantified in patients with heterozygous familial hypercholesterolemia (FH).
  
  
  
  This study estimated the relative risk reduction for CAD and mortality by statins in heterozygous FH patients.
  
  
  
  The authors included all adult heterozygous FH patients, identified by the Dutch screening program for FH between 1994 and 2013, who were free of CAD at baseline. Hospital, pharmacy, and mortality records between 1995 and 2015 were linked to these patients. The primary outcome was the composite of myocardial infarction, coronary revascularization, and death from any cause. The effect of statins (time-varying) was determined using a Cox proportional hazard model, while correcting for the use of other lipid-lowering therapy, thrombocyte aggregation inhibitors, and antihypertensive and antidiabetic medication. The authors applied inverse-probability-for-treatment weighting (IPTW) to account for differences at baseline between statin users and never-users.
  
  
  
  The authors obtained medical records of 2,447 patients, of whom 888 were excluded on the basis of age <18 years or previous CAD. Simvastatin 40 mg and atorvastatin 40 mg accounted for 23.1% and 22.8% of all prescriptions, respectively. Statin users (n = 1,041) experienced 89 CAD events and 17 deaths during 11,674 person-years of follow-up versus statin never-users (n = 518), who had 22 CAD events and 9 deaths during 4,892 person-years (combined rates 8.8 vs. 5.3 per 1,000 person-years, respectively; p < 0.001). After applying IPTW and adjusting for other medications, the hazard ratio of statin use for CAD and all-cause mortality was 0.56 (95% confidence interval: 0.33 to 0.96).
  
  
  
  In patients with heterozygous FH, moderate- to high-intensity statin therapy lowered the risk for CAD and mortality by 44%. This is essential information in all cost-effectiveness studies of this disorder, such as when evaluating reimbursement of new lipid-lowering therapies.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Besseling
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Roeland
authors.initials: R
authors.lastname: Huijgen
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands. Electronic address: j.j.kastelein@amc.nl.
authors.forename: John J P
authors.initials: JJP
authors.lastname: Kastelein
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Hutten
mesh_terms: D000328:Adult; D000069059:Atorvastatin / Q000008:administration & dosage*; D002423:Cause of Death / Q000639:trends; D003324:Coronary Artery Disease / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006579:Heterozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D019821:Simvastatin / Q000008:administration & dosage*; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069059:Atorvastatin; D019821:Simvastatin
keywords: intensity; inverse-probability-of-treatment-weighting; lipid lowering