title: Efficacy and safety of fixed dose combination of atorvastatin and hydroxychloroquine: a randomized, double-blind comparison with atorvastatin alone among Indian patients with dyslipidemia.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of atorvastatin + hydroxychloroquine fixed-dose combination tablets in comparison with atorvastatin alone in treatment of dyslipidemia.
  
  
  METHODS
  This double-blind, randomized, out-patient study was conducted in 328 patients with primary dyslipidemia having low-density lipoprotein cholesterol (LDL-C) ≥ 130 mg/dL (3.37 mmol/L) to ≤ 250 mg/dL (6.48 mmol/L) and triglycerides ≤ 400 mg/dL (4.52 mmol/L). Eligible patients were randomized to receive either atorvastatin 10 mg (n = 167) or atorvastatin 10 mg + hydroxychloroquine 200 mg (n = 161) for 24 weeks.
  
  
  BACKGROUND
  CTRI/2010/091/006138.
  
  
  METHODS
  To compare percentage change in LDL-C, total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to Week 12 and Week 24 between groups. To compare mean change in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), high-sensitivity C-reactive protein (Hs-CRP), and percentage of patients achieving lipid goals at Week 12 and Week 24.
  
  
  RESULTS
  At Week 24, percentage reduction in LDL-C (-32.52 [-36.13 to -28.91] vs -39.54 [-43.25 to -35.83]; p = 0.008), TC (-24.41 [-27.10 to -21.72] vs -29.30 [-32.07 to -26.54]; p = 0.013), and non-HDL-C (-30.37 [-33.71 to -27.04] vs -36.76 [-40.18 to -33.33]; p = 0.009) was significantly greater in combination treated patients. Both the treatments showed a significant reduction in triglycerides at Week 24 from baseline, however, this reduction was not statistically significantly different between treatment groups. No significant change in HDL-C was observed in patients from both the treatment groups. At Week 24, change in HbA1c (0.22 [0.07 to 0.37] vs -0.13 [-0.28 to 0.03]; p = 0.002) and FBG was also statistically significant in favor of combination therapy (0.37 [0.07 to 0.67] vs -0.29 [-0.59 to 0.03]; p = 0.003), whereas no statistically significant difference was observed in change in Hs-CRP (p = 0.310). Significantly more patients from the combination group achieved LDL-C and TC goals. Exploratory analysis in patients with pre-diabetes showed development of diabetes in 8 patients (15.09%) from the monotherapy group and 1 patient (1.96%) from the combination group (p = 0.034). Study medications were generally safe and well tolerated.
  
  
  CONCLUSIONS
  Based on study results and widely reported pleiotropic benefits, hydroxychloroquine could emerge as a potential drug for combination with statins for treatment of dyslipidemia. Long duration studies with larger sample sizes are required to further explore the role of hydroxychloroquine as adjunct to statins in reducing risk of cardiovascular events and prevention of statin-induced diabetes.
authors.affiliation: a a Medical Affairs and Clinical Research Department , Ipca Laboratories Limited , Mumbai , India.
authors.forename: Anil
authors.initials: A
authors.lastname: Pareek
authors.affiliation: b b Clinical Research and Development , Ipca Laboratories Limited , Mumbai , India.
authors.forename: Nitin
authors.initials: N
authors.lastname: Chandurkar
authors.affiliation: c c Department of Medicine , Calicut Medical College and Hospital , Calicut , India.
authors.forename: N K
authors.initials: NK
authors.lastname: Thulaseedharan
authors.affiliation: d d Department of Medicine , Government TD Medical College and Hospital , Alappuzha , India.
authors.forename: R
authors.initials: R
authors.lastname: Legha
authors.affiliation: e e Medilink Hospital and Research Centre , Ahmedabad , India.
authors.forename: Manish
authors.initials: M
authors.lastname: Agarwal
authors.affiliation: f f Department of Medicine , SN Medical College and Hospital , Jodhpur , India.
authors.forename: S L
authors.initials: SL
authors.lastname: Mathur
authors.affiliation: g g Department of Medicine , NKP Salve Institute of Medical Sciences and Lata Mangeshkar Medical College and Hospital , Nagpur , India.
authors.forename: H R
authors.initials: HR
authors.lastname: Salkar
authors.affiliation: h h Department of Medicine , LTMMC and LTMG Hospital , Mumbai , India.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Pednekar
authors.affiliation: i i Dr. Vikas Govind Pai Clinical Research Foundation , Pune , India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Pai
authors.affiliation: j j Associates in Clinical Endocrinology Education and Research , Chennai , India.
authors.forename: Usha
authors.initials: U
authors.lastname: Sriram
authors.affiliation: k k Department of Medicine , Dr. DY Patil Medical College and Hospital , Kolhapur , India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Khyalappa
authors.affiliation: l l Department of Medicine , Government Medical College and SSG Hospital , Vadodara , India.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Parmar
authors.affiliation: m m Diabetes, Obesity and Thyroid Centre , Gwalior , India.
authors.forename: Navneet
authors.initials: N
authors.lastname: Agrawal
authors.affiliation: n n HCG Medi Surge Hospital , Ahmedabad , India.
authors.forename: Urman
authors.initials: U
authors.lastname: Dhruv
authors.affiliation: o o RG Healthcare , Jaipur , India.
authors.forename: Subhash
authors.initials: S
authors.lastname: Saxena
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000069059:Atorvastatin / Q000008:administration & dosage* / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D004338:Drug Combinations; D050171:Dyslipidemias / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006886:Hydroxychloroquine / Q000008:administration & dosage* / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D000069059:Atorvastatin; D002097:C-Reactive Protein; D002784:Cholesterol; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004338:Drug Combinations; D006442:Glycated Hemoglobin; D006886:Hydroxychloroquine; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D014280:Triglycerides
keywords: Atorvastatin; Dyslipidemia; Hydroxychloroquine; Statin-induced diabetes