title: Impact of Switching From High-Efficacy Lipid-Lowering Therapies to Generic Simvastatin on LDL-C Levels and LDL-C Goal Attainment Among High-Risk Primary and Secondary Prevention Populations in the United Kingdom.
abstract: OBJECTIVE
  High cholesterol, especially high low-density lipoprotein cholesterol (LDL-C), is an important risk factor for cardiovascular disease (CVD) morbidity/mortality. Switching from high-efficacy lipid-lowering therapies (HETs) to simvastatin might lead to sub-optimal control of LDL-C. Our objective was to evaluate the impact of switching from HETs to generic simvastatin on LDL-C levels and LDL-C goal attainment among the high-risk primary and secondary prevention populations in the United Kingdom.
  
  
  METHODS
  This retrospective cohort study was conducted using Clinical Practice Research Datalink database. Included were individuals with more than 2 months of prescriptions of the following HETs between August 1, 2004 and December 31, 2008: simvastatin/ezetimibe fixed dose (S/E), simvastatin and ezetimibe co-administration (S+E), atorvastatin and ezetimibe co-administration (A+E), rosuvastatin and ezetimibe co-administration (R+E), rosuvastatin monotherapy, and atorvastatin monotherapy. For each baseline HET, we used analysis of covariance (ANCOVA) to estimate the least squares mean (LSM) difference in the percentage change from baseline in LDL-C between switchers and non-switchers, and logistic regression to estimate the odds ratio of attaining the LDL-C goal (<3 mmol/L for primary prevention and <2 mmol/L for secondary prevention, by JBS2) at follow-up. Propensity score adjusted analyses were conducted to reduce selection bias.
  
  
  RESULTS
  30,148 patients met the eligibility criteria with 83.8% received atorvastatin, 9.5% rosuvastatin and 2.6% S/E and S+E combined. 89.1% of patients switching from atorvastatin switched to an equivalent or higher dose of simvastatin (dose equivalency was determined by relative efficacy of one statin to other statins), while 100% of those switching from simvastatin/ezetimibe and 96.8% of those switching from rosuvastatin switched to lower than equivalent dose of simvastatin. Compared to non-switchers, the adjusted least squares mean differences in the percentage change in LDL-C levels from baseline were 18.74% (p = 0.0003), 16.73% (p < 0.0001), and -0.11% (p = 0.9044) when switching from simvastatin/ezetimibe, rosuvastatin, and atorvastatin, respectively. The odds of LDL-C goal attainment at follow-up among switchers from simvastatin/ezetimibe, rosuvastatin, and atorvastatin were 0.40 (95% CI: 0.23-0.70), 0.36 (95% CI: 0.26-0.51) and 1.03 (95% CI: 0.92-1.15) relative to non-switchers respectively.
  
  
  CONCLUSIONS
  Among the high risk CVD population in UK, switching to simvastatin from HET, especially rosuvastatin and simvastatin/ezetimibe, resulted in an increase in LDL-C levels and lower goal attainment. These historical data reinforce the appropriateness of the changes in the new Joint British Guideline (JBS3) which no longer recommends starting simvastatin 40 mg.
authors.affiliation: Merck & Co, Inc, Whitehouse Station, New Jersey. Electronic address: xiting.cao@merck.com.
authors.forename: Xiting
authors.initials: X
authors.lastname: Cao
authors.affiliation: Merck & Co, Inc, Whitehouse Station, New Jersey.
authors.forename: Flavia
authors.initials: F
authors.lastname: Ejzykowicz
authors.affiliation: Merck & Co, Inc, Whitehouse Station, New Jersey.
authors.forename: Dena R
authors.initials: DR
authors.lastname: Ramey
authors.affiliation: Merck & Co, Inc, Whitehouse Station, New Jersey.
authors.forename: Shiva
authors.initials: S
authors.lastname: Sajjan
authors.affiliation: Merck & Co, Inc, Whitehouse Station, New Jersey.
authors.forename: Baishali M
authors.initials: BM
authors.lastname: Ambegaonkar
authors.affiliation: Merck & Co, Inc, Whitehouse Station, New Jersey.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Mavros
authors.affiliation: Merck & Co, Inc, Whitehouse Station, New Jersey.
authors.forename: Kaan
authors.initials: K
authors.lastname: Tunceli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000069059:Atorvastatin / Q000008:administration & dosage; D002318:Cardiovascular Diseases / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D016568:Drugs, Generic / Q000008:administration & dosage / Q000627:therapeutic use; D000069438:Ezetimibe / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage; D055502:Secondary Prevention; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D006113:United Kingdom
chemical_list: D008078:Cholesterol, LDL; D016568:Drugs, Generic; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D019821:Simvastatin; D000069438:Ezetimibe
keywords: CPRD database; LDL-C; high-efficacy lipid-lowering therapy; retrospective cohort study; simvastatin; switching