Safety and efficacy of statin therapy in patients switched from cyclosporine a to sirolimus after cardiac transplantation.
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.
Aliabadi
Arezu Z
AZ
Department of Cardiothoracic Surgery, Medical University of Vienna, Währinger Gürtel, Vienna, Austria.
Mahr
Stephane
S
Dunkler
Daniela
D
Grömmer
Martina
M
Zimpfer
Daniel
D
Wolner
Ernst
E
Grimm
Michael
M
Zuckermann
Andreas O
AO
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
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