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 .
Anacetrapib as lipid-modifying therapy in patients with heterozygous familial hypercholesterolaemia (REALIZE): a randomised, double-blind, placebo-controlled, phase 3 study
BACKGROUND Present guidelines emphasise the importance of low concentrations of LDL cholesterol ( LDL-C ) in patients with familial hypercholesterolaemia . In most patients with the disease , however , these concentrations are not achieved with present treatments , so additional treatment is therefore warranted . Inhibition of cholesteryl ester transfer protein has been shown to reduce LDL-C concentrations in addition to regular statin treatment in patients with hypercholesterolaemia or at high risk of cardiovascular disease . We aim ed to investigate the safety and efficacy of anacetrapib , a cholesteryl ester transfer protein inhibitor , in patients with heterozygous familial hypercholesterolaemia . METHODS In this multicentre , r and omised , double-blind , placebo-controlled , phase 3 study , patients aged 18 - 80 years with a genotype-confirmed or clinical diagnosis of heterozygous familial hypercholesterolaemia , on optimum lipid-lowering treatment for at least 6 weeks , and with an LDL-C concentration of 2·59 mmol/L or higher without cardiovascular disease or 1·81 mmol/L or higher with cardiovascular disease from 26 lipid clinics across nine countries were eligible . We r and omly allocated participants with a computer-generated allocation schedule ( 2:1 ; block size of six ; no stratification ) to oral anacetrapib 100 mg or placebo for 52 weeks , with a 12 week post-treatment follow-up afterwards . We masked patients , care providers , and those assessing outcomes to treatment groups throughout the study . The primary outcome was percentage change from baseline in LDL-C concentration . We did analysis using a constrained longitudinal repeated measures model . This trial is registered with Clinical Trials.gov , number NCT01524289 . FINDINGS Between Feb 10 , 2012 , and Feb 12 , 2014 , we r and omly allocated 204 patients to anacetrapib and 102 to placebo . One patient in the anacetrapib group did not receive the drug . At week 52 , anacetrapib  reduced mean LDL-C concentration from 3·3 mmol/L ( SD 0·8 ) to 2·1 mmol/L ( 0·8 ; percentage change 36·0 % [ 95 % CI -39·5 to -32·5 ] compared with an increase with placebo from 3·4 mmol/L ( 1·2 ) to 3·5 mmol/L ( 1·6 ; percentage change 3·7 % [ -1·2 to 8·6 ] , with a difference in percentage change between anacetrapib and placebo of -39·7 % ( 95 % CI -45·7 to -33·7 ; p<0·0001 ) . The number of cardiovascular events was increased in patients given anacetrapib compared with those given placebo ( 4 [ 2 % ] of 203 vs none [ 0 % ] of 102 ; p=0·1544 ) , but the proportion with adverse events leading to discontinuation was similar ( 12 [ 6 % ] of 203 vs five [ 5 % ] of 102 ) . INTERPRETATION In patients with heterozygous familial hypercholesterolaemia , treatment with anacetrapib for 1 year was well tolerated and result ed in substantial reductions in LDL-C concentration . Whether this change leads to a reduction of cardiovascular events will be answered in an outcome study . FUNDING Merck & Co ,
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 .