title: Safety and efficacy of statin therapy in patients switched from cyclosporine a to sirolimus after cardiac transplantation.
abstract: BACKGROUND
  Statins are an established therapy after cardiac transplantation. Sirolimus (Srl) has been used successfully in cardiac transplant patients. However, potential side effects are hyperlipidemia and interactions with statins. The aim of the study was to evaluate the safety and efficacy of statin therapy after switch to a Srl-based immunosuppression.
  
  
  METHODS
  Ninety-eight long-term patients were switched from Cyclosporine A to Srl. Also all patients received mycophenolate mofetil alone or mycophenolate mofetil plus steroid therapy. Reasons for switch were renal dysfunction, graftvasculopathy, or skin cancer. Patients were switched 7.8+/-4.7 years after transplant. Total observation period was 12 months before and after switch, respectively. Safety evaluation consisted of regular measurements of CPK and liver enzymes to evaluate the incidence myopathy and hepatoxicity. Efficacy analysis was performed by serial blood lipid assessments (low-density lipoprotein, high-density lipoprotein, total cholesterol, and triglycerides).
  
  
  RESULTS
  Forty-three percentage of patients received atorvastatin, 38% pravastatin, and 18% other drugs or therapy changes. Most lipid blood levels increased significantly after switch (cholesterol: 192.9+/-38.6 mg/dL vs. 221.8+/-49.2 mg/dL, P<0.0001; low-density lipoprotein: 108.0+/-35.6 mg/dL vs. 123.8+/-37.9 mg/dL, P<0.0001; and triglycerides: 178.3+/-88.2 mg/dL vs. 225.5+/-139.1 mg/dL, P<0.0001). Blood lipid levels after switch were not associated with statin type. Overall safety was acceptable, although incidence of myopathy doubled after switch (n=20 vs. 40; P<0.01). However, most cases were asymptomatic CPK elevations in the pravastatin group. Hepatotoxicity rate was 4% and only temporary.
  
  
  CONCLUSIONS
  Statin therapy after switch from cyclosporine A to Srl in long-term cardiac transplant patients is safe. However, regular testing of blood lipids and CPK should be mandatory.
authors.affiliation: Department of Cardiothoracic Surgery, Medical University of Vienna, Währinger Gürtel, Vienna, Austria.
authors.forename: Arezu Z
authors.initials: AZ
authors.lastname: Aliabadi
authors.forename: Stephane
authors.initials: S
authors.lastname: Mahr
authors.forename: Daniela
authors.initials: D
authors.lastname: Dunkler
authors.forename: Martina
authors.initials: M
authors.lastname: Grömmer
authors.forename: Daniel
authors.initials: D
authors.lastname: Zimpfer
authors.forename: Ernst
authors.initials: E
authors.lastname: Wolner
authors.forename: Michael
authors.initials: M
authors.lastname: Grimm
authors.forename: Andreas O
authors.initials: AO
authors.lastname: Zuckermann
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000368:Aged; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use*; D050171:Dyslipidemias / Q000453:epidemiology / Q000517:prevention & control; D005260:Female; D016027:Heart Transplantation / Q000276:immunology* / Q000502:physiology*; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000453:epidemiology / Q000517:prevention & control; D017035:Pravastatin / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D012449:Safety; D020123:Sirolimus / Q000627:therapeutic use*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D000305:Adrenal Cortex Hormones; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D011758:Pyrroles; D014280:Triglycerides; D016572:Cyclosporine; D002784:Cholesterol; D000069059:Atorvastatin; D017035:Pravastatin; D020123:Sirolimus