Conclusions Fibrates have a significantly greater effect in reducing plasma Lp(a ) concentrations than statins .
Addition of fibrates to statins can enhance the Lp(a)-lowering effect of statins
Background Raised plasma lipoprotein(a ) ( Lp(a ) ) concentration is an independent and causal risk factor for atherosclerotic cardiovascular disease .
Several types of pharmacological approaches are under evaluation for their potential to reduce plasma Lp(a ) levels .
There is suggestive evidence that statins and fibrates , two frequently employed lipid-lowering drugs , can lower plasma Lp(a ) .
The present study aims to compare the efficacy of fibrates and statins in reducing plasma concentrations of Lp(a ) using a meta- analysis of r and omized head-to-head trials .
Genetically elevated lipoprotein(a) and increased risk of myocardial infarction.
CONTEXT High levels of lipoprotein(a ) are associated with increased risk of myocardial infa rct ion ( MI ) . OBJECTIVE To assess whether genetic data are consistent with this association being causal . DESIGN , SETTING , AND PARTICIPANTS Three studies of white individuals from Copenhagen , Denmark , were used : the Copenhagen City Heart Study ( CCHS ) , a prospect i ve general population study with 16 years of follow-up ( 1991 - 2007 , n = 8637 , 599 MI events ) ; the Copenhagen General Population Study ( CGPS ) , a cross-sectional general population study ( 2003 - 2006 , n = 29 388 , 994 MI events ) ; and the Copenhagen Ischemic Heart Disease Study ( CIHDS ) , a case-control study ( 1991 - 2004 , n = 2461 , 1231 MI events ) . MAIN OUTCOME MEASURES Plasma lipoprotein(a ) levels , lipoprotein(a ) kringle IV type 2 ( KIV-2 ) size polymorphism genotype , and MIs recorded from 1976 through July 2007 for all participants . RESULTS In the CCHS , multivariable-adjusted hazard ratios ( HRs ) for MI for elevated lipoprotein(a ) levels were 1.2 ( 95 % confidence interval [ CI ] , 0.9 - 1.6 ; events/10,000 person-years , 59 ) for levels between the 22nd and 66th percentile , 1.6 ( 95 % CI , 1.1 - 2.2 ; events/10,000 person-years , 75 ) for the 67th to 89th percentile , 1.9 ( 95 % CI , 1.2 - 3.0 ; events/10,000 person-years , 84 ) for the 90th to 95th percentile , and 2.6 ( 95 % CI , 1.6 - 4.1 ; events/10,000 person-years , 108 ) for levels greater than the 95th percentile , respectively , vs levels less than the 22nd percentile ( events/10,000 person-years , 55 ) ( trend P < .001 ) . Numbers of KIV-2 repeats ( sum of repeats on both alleles ) ranged from 6 to 99 and on analysis of variance explained 21 % and 27 % of all variation in plasma lipoprotein(a ) levels in the CCHS and CGPS , respectively . Mean lipoprotein(a ) levels were 56 , 31 , 20 , and 15 mg/dL for the first , second , third , and fourth quartiles of KIV-2 repeats in the CCHS , respectively ( trend P < .001 ) ; corresponding values in the CGPS were 60 , 34 , 22 , and 19 mg/dL ( trend P < .001 ) . In the CCHS , multivariable-adjusted HRs for MI were 1.5 ( 95 % CI , 1.2 - 1.9 ; events/10,000 person-years , 75 ) , 1.3 ( 95 % CI , 1.0 - 1.6 ; events/10,000 person-years , 66 ) , and 1.1 ( 95 % CI , 0.9 - 1.4 ; events/10,000 person-years , 57 ) for individuals in the first , second , and third quartiles , respectively , as compared with individuals in the fourth quartile of KIV-2 repeats ( events/10,000 person-years , 51 ) ( trend P < .001 ) . Corresponding odds ratios were 1.3 ( 95 % CI , 1.1 - 1.5 ) , 1.1 ( 95 % CI , 0.9 - 1.3 ) , and 0.9 ( 95 % CI , 0.8 - 1.1 ) in the CGPS ( trend P = .005 ) , and 1.4 ( 95 % CI , 1.1 - 1.7 ) , 1.2 ( 95 % CI , 1.0 - 1.6 ) , and 1.3 ( 95 % CI , 1.0 - 1.6 ) in the CIHDS ( trend P = .01 ) . Genetically elevated lipoprotein(a ) was associated with an HR of 1.22 ( 95 % CI , 1.09 - 1.37 ) per doubling of lipoprotein(a ) level on instrumental variable analysis , while the corresponding value for plasma lipoprotein(a ) levels on Cox regression was 1.08 ( 95 % CI , 1.03 - 1.12 ) . CONCLUSION These data are consistent with a causal association between elevated lipoprotein(a ) levels and increased risk of MI
Conclusions Fibrates have a significantly greater effect in reducing plasma Lp(a ) concentrations than statins .
Addition of fibrates to statins can enhance the Lp(a)-lowering effect of statins
Background Raised plasma lipoprotein(a ) ( Lp(a ) ) concentration is an independent and causal risk factor for atherosclerotic cardiovascular disease .
Several types of pharmacological approaches are under evaluation for their potential to reduce plasma Lp(a ) levels .
There is suggestive evidence that statins and fibrates , two frequently employed lipid-lowering drugs , can lower plasma Lp(a ) .
The present study aims to compare the efficacy of fibrates and statins in reducing plasma concentrations of Lp(a ) using a meta- analysis of r and omized head-to-head trials .