title: Evaluation of sexual dimorphism in the efficacy and safety of simvastatin/atorvastatin therapy in a southern Brazilian cohort.
abstract: BACKGROUND
  Dyslipidemia is the primary risk factor for cardiovascular disease, and statins have been effective in controlling lipid levels. Sex differences in the pharmacokinetics and pharmacodynamics of statins contribute to interindividual variations in drug efficacy and toxicity.
  
  
  OBJECTIVE
  To evaluate the presence of sexual dimorphism in the efficacy and safety of simvastatin/atorvastatin treatment.
  
  
  METHODS
  Lipid levels of 495 patients (331 women and 164 men) were measured at baseline and after 6 ± 3 months of simvastatin/atorvastatin treatment to assess the efficacy and safety profiles of both drugs.
  
  
  RESULTS
  Women had higher baseline levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) compared with men (p < 0.0001). After treatment, women exhibited a greater decrease in plasma TC and LDL-C levels compared with men. After adjustment for covariates, baseline levels of TC and LDL-C influenced more than 30% of the efficacy of lipid-lowering therapy (p < 0.001), regardless of sex. Myalgia [with or without changes in creatine phosphokinase (CPK) levels] occurred more frequently in women (25.9%; p = 0.002), whereas an increase in CPK and/or abnormal liver function was more frequent in in men (17.9%; p = 0.017).
  
  
  CONCLUSIONS
  Our results show that baseline TC and LDL-C levels are the main predictors of simvastatin/atorvastatin therapy efficacy, regardless of sex. In addition, they suggest the presence of sexual dimorphism in the safety of simvastatin/atorvastatin. The effect of sex differences on receptors, transporter proteins, and gene expression pathways needs to be better evaluated and characterized to confirm these observations.
authors.affiliation: Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Lisiane
authors.initials: L
authors.lastname: Smiderle
authors.affiliation: Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Luciana O
authors.initials: LO
authors.lastname: Lima
authors.affiliation: Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Mara Helena
authors.initials: MH
authors.lastname: Hutz
authors.affiliation: Centro de Diagnóstico Cardiológico, Porto Alegre, RS, Brazil.
authors.forename: Cézar Roberto
authors.initials: CR
authors.lastname: Van der Sand
authors.affiliation: Centro de Diagnóstico Cardiológico, Porto Alegre, RS, Brazil.
authors.forename: Luiz Carlos
authors.initials: LC
authors.lastname: Van der Sand
authors.affiliation: Centro de Diagnóstico Cardiológico, Porto Alegre, RS, Brazil.
authors.forename: Maria Elvira Wagner
authors.initials: ME
authors.lastname: Ferreira
authors.affiliation: Centro de Diagnóstico Cardiológico, Porto Alegre, RS, Brazil.
authors.forename: Renan Canibal
authors.initials: RC
authors.lastname: Pires
authors.affiliation: Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Silvana
authors.initials: S
authors.lastname: Almeida
authors.affiliation: Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Marilu
authors.initials: M
authors.lastname: Fiegenbaum
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000494:pharmacology*; D000069059:Atorvastatin; D001938:Brazil; D002784:Cholesterol / Q000097:blood; D003402:Creatine Kinase / Q000187:drug effects; D005260:Female; D006538:Heptanoic Acids / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D063806:Myalgia / Q000209:etiology; D011446:Prospective Studies; D011758:Pyrroles / Q000009:adverse effects / Q000494:pharmacology*; D012737:Sex Factors; D019821:Simvastatin / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin; D019821:Simvastatin; D003402:Creatine Kinase