Conclusions : CETP inhibitors are not associated with an increased risk of MACE or all-cause mortality .
There is a trend towards small reductions in nonfatal MI and cardiovascular death , though the clinical importance of such reductions is likely modest
Background : Cholesteryl ester transfer protein ( CETP ) inhibitors increase serum high-density lipoprotein cholesterol ( HDL-c ) concentration ; however , their impact on cardiovascular outcomes is not clear .
This systematic review examines the effect of CETP inhibitors on serum lipid profiles , cardiovascular events , and all-cause mortality .
Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidaemia (TULIP): a randomised, double-blind, placebo-controlled phase 2 trial
BACKGROUND Dyslipidaemia remains a significant risk factor for cardiovascular disease and additional lipid-modifying treatments are warranted to further decrease the cardiovascular disease burden . We assessed the safety , tolerability and efficacy of a novel cholesterol esterase transfer protein ( CETP ) inhibitor TA-8995 in patients with mild dyslipidaemia . METHODS In this r and omised , double-blind , placebo-controlled , parallel-group phase 2 trial , we recruited patients ( aged 18 - 75 years ) from 17 sites ( hospitals and independent clinical research organisations ) in the Netherl and s and Denmark with fasting LDL cholesterol levels between 2·5 mmol/L and 4·5 mmol/L , HDL cholesterol levels between 0·8 and 1·8 mmol/L and triglyceride levels below 4·5 mmol/L after washout of lipid-lowering treatments . Patients were r and omly allocated ( 1:1 ) by a computer-generated r and omisation schedule to receive one of the following nine treatments : a once a day dose of 1 mg , 2·5 mg , 5 mg , or 10 mg TA-8995 or matching placebo ; 10 mg TA-8995 plus 20 mg atorvastatin ; 10 mg TA-8995 plus 10 mg rosuvastatin or 20 mg atorvastatin or 10 mg rosuvastatin alone . We overencapsulated statins to achieve masking . The primary outcome was percentage change in LDL cholesterol and HDL cholesterol from baseline at week 12 , analysed by intention to treat . This study is registered with Clinical Trials.gov , number NCT01970215 . FINDINGS Between Aug 15 , 2013 , and Jan 10 , 2014 , 364 patients were enrolled . At week 12 , LDL cholesterol levels were reduced by 27·4 % in patients assigned to the 1 mg dose , 32·7 % in patients given the 2·5 mg dose , 45·3 % in those given the 5 mg dose , and 45·3 % in those given the 10 mg dose ( p<0·0001 ) . LDL cholesterol levels were reduced by 68·2 % in patients given 10 mg TA-8995 plus atorvastatin , and by 63·3 % in patients given rosuvastatin plus 10 mg TA-8995 ( p<0·0001 ) . A daily dose of 1 mg TA-8995  increased HDL cholesterol levels by 75·8 % , 2·5 mg by 124·3 % , 5 mg by 157·1 % , and 10 mg dose by 179·0 % ( p<0·0001 ) . In patients receiving 10 mg TA-8995 and 20 mg  atorvastatin HDL cholesterol levels increased by 152·1 % and in patients receiving 10 mg TA-8995 and 10 mg rosuvastatin by 157·5 % . We recorded no serious adverse events or signs of liver or muscle toxic effects . INTERPRETATION TA-8995 , a novel CETP inhibitor , is well tolerated and has beneficial effects on lipids and apolipoproteins in patients with mild dyslipidaemia . A cardiovascular disease outcome trial is needed to translate these effects into a reduction of cardiovascular disease events . FUNDING Dezima
Conclusions : CETP inhibitors are not associated with an increased risk of MACE or all-cause mortality .
There is a trend towards small reductions in nonfatal MI and cardiovascular death , though the clinical importance of such reductions is likely modest
Background : Cholesteryl ester transfer protein ( CETP ) inhibitors increase serum high-density lipoprotein cholesterol ( HDL-c ) concentration ; however , their impact on cardiovascular outcomes is not clear .
This systematic review examines the effect of CETP inhibitors on serum lipid profiles , cardiovascular events , and all-cause mortality .