New phase III data demonstrated that Pitavastatin ( Livalo ) is non-inferior to Atorvastatin ( Lipitor ) and Simvastatin ( Zocor ) at usual therapeutic doses in patients with primary hypercholesterolemia or combined dyslipidemia, as measured by reduction of low density lipoprotein cholesterol ( LDL-C ) from baseline.

LDL-C target attainment data was similar when comparing Pitavastatin to first-line drugs Atorvastatin and Simvastatin, although Pitavastatin demonstrated significantly higher LDL-C target attainment compared to Simvastatin in the lower dose study-arm ( Pitavastatin 2 mg vs Simvastatin 20 mg ) ( p=0.047 ).
Furthermore, continued gradual increases in high density lipoprotein cholesterol ( HDL-C ) were observed over the long-term, supported by data from a 52 week extension study.
Pitavastatin also demonstrated a favourable safety and tolerability profile to 52 weeks, the latter exemplified by a low rate of discontinuations due to adverse events, which were comparable to those with Simvastatin or Atorvastatin.

The primary objective of the two phase III, double blind, active-controlled studies was to demonstrate non-inferiority of Pitavastatin to Atorvastatin and Simvastatin, as measured by the reduction of LDL-C.
After a 6-8 week wash-out period, patients with primary hypercholesterolemia or combined dyslipidemia who had an average LDL-C > 4.2 mmol/L ( 160 mg/dL ) and > 5.7 mmol/L ( 220 mg/dL ) and a triglycerides ( TG ) level of > 4.6 mmol/L ( 400 mg/dL ) were treated for 12-week duration as follows:

• Study 1: 830 patients ( 46% males; mean 58 years ) were randomised to one of four treatment groups, Pitavastatin 2 mg, Pitavastatin 4 mg, Atorvastatin 10 mg or Atorvastatin 20 mg ( all doses QD ) using up-titration for higher doses.

• Study 2: 857 patients ( 39% males; mean 58 years ) were randomised to one of four treatment groups, Pitavastatin 2 mg, Pitavastatin 4 mg, Simvastatin 20 mg or Simvastatin 40 mg ( all doses QD ) using up-titration for higher doses.

Secondary objectives were to assess National Cholesterol Education Program ( NCEP ) and European Atherosclerosis Society ( EAS ) LDL-C target attainment, other lipid and lipoprotein fractions, safety and tolerability.

A total of 1355 patients ( 42.5% males; mean age 58.6 years ) who completed the two initial studies took part in an open-label extension to assess the long-term safety and tolerability of Pitavastatin 4 mg ( QD ) for up to 52 weeks.
Secondary objectives were to assess NCEP and EAS LDL-C target attainment, other lipid and lipoprotein fractions.

Pitavastatin was well tolerated to 52 weeks; no serious treatment-emergent adverse event ( TEAE ) was related to Pitavastatin, with the most commonly reported TEAEs being increased blood creatinine kinase ( 5.8% ), nasopharyngitis ( 5.4% ) and myalgia ( 4.1% ). Additionally, there were no clinically significant abnormalities in routine laboratory variables, urinalysis, vital signs or 12-lead ECG.

Continued gradual increases in HDL-C were observed over 52 weeks and reductions in LDL-C were sustained over 52 weeks thus demonstrating sustained efficacy of Pitavastatin over the long-term.

Source: European Society of Cardiology ( ESC ) Congress, 2009

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