TY - JOUR
T1 - Very low levels of atherogenic lipoproteins and the risk for cardiovascular events
T2 - A meta-analysis of statin trials
AU - Boekholdt, S. Matthijs
AU - Hovingh, G. Kees
AU - Mora, Samia
AU - Arsenault, Benoit J.
AU - Amarenco, Pierre
AU - Pedersen, Terje R.
AU - Larosa, John C.
AU - Waters, David D.
AU - Demicco, David A.
AU - Simes, R. John
AU - Keech, Antony C.
AU - Colquhoun, David
AU - Hitman, Graham A.
AU - Betteridge, D. John
AU - Clearfield, Michael B.
AU - Downs, John R.
AU - Colhoun, Helen M.
AU - Gotto, Antonio M.
AU - Ridker, Paul M.
AU - Grundy, Scott M.
AU - Kastelein, John J P
N1 - Funding Information:
This meta-analysis was not supported by any funding. The contributing trials were funded by their respective sponsors and provided the requested data. They did not play any role in the statistical analysis, interpretation of the data, writing of the manuscript, or the decision to submit the manuscript. Dr. Hovingh is funded by a Veni grant (project number 91612122) from the Netherlands Organisation for Scientific Research . Drs. Boekholdt, Hovingh, and Arsenault have received consulting fees from Pfizer Inc. Dr. Hovingh has served on the speakers’ bureaus of Amgen Europe B.V., Genzyme Netherlands, Merck Sharp & Dohme Corporation, Pfizer B.V., Roche Nederland B.V., and Sanofi-Aventis Netherlands B.V. Dr. Mora has received honoraria grants through her institution from Atherotech Diagnostics , AstraZeneca Pharma U.S., Inc. , and the National Heart, Lung, and Blood Institute (HL117861); consulting fees from Cerenis Therapeutics, Genzyme Corporation, Pfizer Inc., and Quest Diagnostics Inc.; and travel accommodations/meeting expenses from Pfizer Inc.; and has served on the speakers' bureaus of Abbott Laboratories and AstraZeneca Pharma U.S., Inc. Dr. Amarenco has served on the speakers’ bureaus of AstraZeneca France, Boehringer Ingelheim France S.A.S., Merck KGaA, Pfizer Inc., Sanofi-Aventis, and the government of France; and has received consulting fees from AstraZeneca France, Bayer S.A.S., Boehringer France S.A.S., Boston Scientific–France, Bristol-Myers Squibb Agen, Daiichi Sankyo France S.A.S., Edwards Lifesciences S.A.S., Kowa Europe GmbH, H. Lundbeck A/S, Merck KGaA, and Pfizer Inc. Dr. LaRosa has received consulting fees from Amgen Inc. and Pfizer Inc.; and travel expenses from Pfizer Inc. Dr. Pedersen has received honoraria grants and/or served on the speakers’ bureaus of AstraZeneca Pharma U.S., Inc., Merck Sharp & Dohme Corporation, Pfizer Inc., and Roche Therapeutics Inc. Dr. Waters has received consulting fees from Anthera Pharmaceuticals Inc., Genentech U.S.A., Inc., Pfizer Inc., Roche Therapeutics Inc., and Laboratoires Servier; has served on the speakers’ bureaus of Pfizer Inc. and Zydus Cadila Healthcare Ltd. (Medica); and has participated in committees of clinical trials sponsored by Aegerion Pharmaceuticals, Inc., BioSante Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., and Sanofi-Aventis. Dr. DeMicco is an employee of, and holds stock options in, Pfizer Inc. Prof. Keech has received honoraria grants from and/or served on the speakers' bureaus and/or advisory boards of Abbott Australasia Pty. Ltd., AstraZeneca Australia, Bristol-Myers Squibb Australia, Eli Lilly Australia, Merck KGaA, Novartis A.G., Pfizer Inc., Roche Products Pty. Ltd., and Solvay Interox Pty. Ltd. Dr. Hitman has received consulting fees from and/or served on the speakers’ bureaus of AstraZeneca, Eli Lilly and Co. Ltd., GlaxoSmithKline plc., Merck Sharp & Dohme Ltd., Novo Nordisk Ltd., OSI Pharmaceuticals Ltd., Pfizer Inc., and Takeda U.K. Ltd.; and has received honoraria grants from Parke-Davis and Eli Lilly and Co., Ltd. Dr. Betteridge has served on the speakers' bureaus and/or advisory boards for Aegerion Pharmaceuticals, Inc., Amgen Europe B.V., AstraZeneca, Janssen Ltd., Kowa Europe GmbH, Merck Sharp & Dohme Ltd., Pfizer Inc., Roche Products Ltd., Sanofi-Synthelabo Ltd., and Takeda U.K. Ltd. Dr. Clearfield has received honoraria for consulting on the advisory boards for AstraZeneca Pharma U.S., Inc., and Merck Sharp & Dohme Corporation. Dr. Colhoun has received honoraria grants through the E.U. Innovative Medicines Initiative from AstraZeneca , Boehringer Ingelheim Ltd. U.K. , Eli Lilly and Co., Ltd. , JRDF , Pfizer Inc. , Roche Products Ltd. , and Sanofi-Aventis ; consulting fees from Eli Lilly and Co., Ltd., Novartis Pharmaceuticals U.K. Ltd., Pfizer Inc., and Sanofi-Aventis; has served on the speakers’ bureaus of, and received travel expenses from, Pfizer Inc.; served on the advisory boards of Eli Lilly and Co., Ltd., Novartis Pharmaceuticals U.K. Ltd., Pfizer Inc., and Sanofi-Aventis; holds stock options in Roche Products Ltd.; and has participated in committees of clinical trials sponsored by Eli Lilly and Co., Ltd., JDRF, Novartis Pharmaceuticals U.K. Ltd., and Sanofi-Aventis. Dr. Gotto has received consulting fees from Roche Products Ltd., Janssen Pharmaceuticals, Inc., Kowa Pharmaceuticals America, Inc., Merck & Co., Inc., and Roche Therapeutics Inc.; has been a member of the boards of directors for Aegerion Pharmaceuticals, Inc. and Arisaph Pharmaceuticals, Inc.; and has been a member of the scientific advisory boards for DuPont, Haptocure Ltd., vascuVis Inc., and Vatera Healthcare Partners. Dr. Ridker has received honoraria grants from AstraZeneca Pharma U.S., Inc., Novartis A.G., and Pfizer Inc.; consulting fees from Abbott Laboratories, Boehringer-Ingelheim Pharmaceuticals, Isis Pharmaceuticals, Inc., Merck Sharp & Dohme Corporation, and Vascular Biogenics Ltd.; has been a member of the scientific advisory board for Boston Heart Diagnostics Corporation, Janssen Pharmaceuticals, Inc., Isis Pharmaceuticals, Inc., Merck Sharp & Dohme Corporation, and Pfizer Inc.; has received honoraria grants to his institution from Amgen Inc.; and is listed as a co-inventor on patents held by the Brigham and Women’s Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease and diabetes and that have been licensed to AstraZeneca Pharma U.S., Inc. and Siemens Corporation. Dr. Kastelein has received honoraria for serving on the speakers’ bureaus of AstraZeneca, Genzyme Australia, Labortoires Isispharma, Kowa Australia Pty. Ltd., Merck Sharp & Dohme Pty. Ltd., Novartis Pharmaceuticals Australia Pty. Ltd., Pfizer Inc., and Roche Products Pty. Ltd. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
PY - 2014/8/5
Y1 - 2014/8/5
N2 - Background Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease risk is not well-documented. Objectives The aim of this meta-analysis was to evaluate: 1) the interindividual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), or apolipoprotein B (apoB) levels achieved with statin therapy; 2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy; and 3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and cardiovascular disease risk. Methods This meta-analysis used individual patient data from 8 randomized controlled statin trials, in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Results Among 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large interindividual variability in the reductions of LDL-C, non-HDL-C, and apoB achieved with a fixed statin dose. More than 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target <70 mg/dl. Compared with patients who achieved an LDL-C >175 mg/dl, those who reached an LDL-C 75 to <100 mg/dl, 50 to <75 mg/dl, and <50 mg/dl had adjusted hazard ratios for major cardiovascular events of 0.56 (95% confidence interval [CI]: 0.46 to 0.67), 0.51 (95% CI: 0.42 to 0.62), and 0.44 (95% CI: 0.35 to 0.55), respectively. Similar associations were observed for non-HDL-C and apoB. Conclusions The reductions of LDL-C, non-HDL-C, and apoB levels achieved with statin therapy displayed large interindividual variation. Among trial participants treated with high-dose statin therapy, >40% did not reach an LDL-C target <70 mg/dl. Patients who achieve very low LDL-C levels have a lower risk for major cardiovascular events than do those achieving moderately low levels.
AB - Background Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease risk is not well-documented. Objectives The aim of this meta-analysis was to evaluate: 1) the interindividual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), or apolipoprotein B (apoB) levels achieved with statin therapy; 2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy; and 3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and cardiovascular disease risk. Methods This meta-analysis used individual patient data from 8 randomized controlled statin trials, in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Results Among 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large interindividual variability in the reductions of LDL-C, non-HDL-C, and apoB achieved with a fixed statin dose. More than 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target <70 mg/dl. Compared with patients who achieved an LDL-C >175 mg/dl, those who reached an LDL-C 75 to <100 mg/dl, 50 to <75 mg/dl, and <50 mg/dl had adjusted hazard ratios for major cardiovascular events of 0.56 (95% confidence interval [CI]: 0.46 to 0.67), 0.51 (95% CI: 0.42 to 0.62), and 0.44 (95% CI: 0.35 to 0.55), respectively. Similar associations were observed for non-HDL-C and apoB. Conclusions The reductions of LDL-C, non-HDL-C, and apoB levels achieved with statin therapy displayed large interindividual variation. Among trial participants treated with high-dose statin therapy, >40% did not reach an LDL-C target <70 mg/dl. Patients who achieve very low LDL-C levels have a lower risk for major cardiovascular events than do those achieving moderately low levels.
KW - apolipoprotein B
KW - LDL-cholesterol
KW - meta-analysis
KW - non-HDL-cholesterol
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U2 - 10.1016/j.jacc.2014.02.615
DO - 10.1016/j.jacc.2014.02.615
M3 - Article
C2 - 25082583
AN - SCOPUS:84905189482
VL - 64
SP - 485
EP - 494
JO - Journal of the American College of Cardiology.
JF - Journal of the American College of Cardiology.
SN - 0735-1097
IS - 5
ER -