Achievement of Dual Low-Density Lipoprotein Cholesterol and High-Sensitivity C-Reactive Protein Targets More Frequent With the Addition of Ezetimibe to Simvastatin and Associated With Better Outcomes in IMPROVE-IT

被引:275
作者
Bohula, Erin A. [1 ]
Giugliano, Robert P. [1 ]
Cannon, Christopher P. [1 ]
Zhou, Jing [1 ]
Murphy, Sabina A. [1 ]
White, Jennifer A. [2 ]
Tershakovec, Andrew M. [3 ]
Blazing, Michael A. [2 ]
Braunwald, Eugene [1 ]
机构
[1] Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA
[2] Duke Clin Res Inst, Durham, NC USA
[3] Merck, Kenilworth, NJ USA
关键词
acute coronary syndrome; cholesterol; LDL; C-reactive protein; ezetimibe; hydroxymethylglutaryl-CoA reductase inhibitors; secondary prevention; STATIN THERAPY; EFFICACY; INFLAMMATION; SAFETY; MONOTHERAPY; DISEASE; TRIALS; RISK; PARTICIPANTS; ATORVASTATIN;
D O I
10.1161/CIRCULATIONAHA.115.018381
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Statins lower low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hs-CRP); addition of ezetimibe to statins further reduces LDL-C and hs-CRP. An analysis of the relationship between achieved LDL-C and hs-CRP targets and outcomes for simvastatin and ezetimibe/simvastatin was prespecified in Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT). Methods and Results-The IMPROVE-IT trial randomly assigned 18 144 patients stabilized after acute coronary syndrome to simvastatin or ezetimibe/simvastatin. LDL-C and hs-CRP were measured at baseline and 1 month after randomization. Outcomes were assessed in those achieving one or both of the prespecified targets of LDL-C<70 mg/dL and hs-CRP<2 mg/L versus achieving neither target, adjusting for differences in baseline characteristics. An exploratory analysis examined targets of LDL-C<50 mg/dL and hs-CRP<1 mg/L. Patients meeting both targets at baseline, with no 1-month values, or with end points before 1 month were excluded. Of 15 179 patients, 39% achieved the dual LDL-C (<70 mg/dL) and hs-CRP (<2 mg/L) targets at 1 month, 14% met neither target, 14% met only the hs-CRP target, and 33% met only the LDL-C target. Those achieving dual targets had lower primary end point rates than those meeting neither target (cardiovascular death, major coronary event, or stroke; 38.9% versus 28.0%; adjusted hazard ratio, 0.73; 0.66-0.81; P<0.001). More patients treated with ezetimibe/simvastatin met dual targets than those treated with simvastatin alone (50% versus 29%, P<0.001). The association of dual-target attainment with improved outcomes was similar irrespective of treatment assignment (P-interaction=0.65). Similar findings were observed using the exploratory targets. Conclusions-Significantly more patients treated with ezetimibe/simvastatin met prespecified and exploratory dual LDL-C and hs-CRP targets than patients treated with simvastatin alone. Reaching both LDL-C and hs-CRP targets was associated with improved outcomes after multivariable adjustment.
引用
收藏
页码:1224 / 1233
页数:10
相关论文
共 34 条
[1]   Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials [J].
Baigent, C. ;
Blackwell, L. ;
Emberson, J. ;
Holland, L. E. ;
Reith, C. ;
Bhala, N. ;
Peto, R. ;
Barnes, E. H. ;
Keech, A. ;
Simes, J. ;
Collins, R. .
LANCET, 2010, 376 (9753) :1670-1681
[2]   Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins [J].
Baigent, C ;
Keech, A ;
Kearney, PM ;
Blackwell, L ;
Buck, G ;
Pollicino, C ;
Kirby, A ;
Sourjina, T ;
Peto, R ;
Collins, R ;
Simes, J .
LANCET, 2005, 366 (9493) :1267-1278
[3]   Efficacy and safety of ezetimibe co-administered with simvastatin compared with atorvastatin in adults with hypercholesterolemia [J].
Ballantyne, CM ;
Blazing, MA ;
King, TR ;
Brady, WE ;
Palmisano, J .
AMERICAN JOURNAL OF CARDIOLOGY, 2004, 93 (12) :1487-1494
[4]   Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): Comparison of ezetimbe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes [J].
Cannon, Christopher P. ;
Giugliano, Robert P. ;
Blazing, Michael A. ;
Harrington, Robert A. ;
Peterson, John L. ;
Sisk, Christine McCrary ;
Strony, John ;
Musliner, Thomas A. ;
McCabe, Carolyn H. ;
Veltri, Enrico ;
Braunwald, Eugene ;
Califf, Robert M. .
AMERICAN HEART JOURNAL, 2008, 156 (05) :826-832
[5]   Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes [J].
Cannon, Christopher P. ;
Blazing, Michael A. ;
Giugliano, Robert P. ;
McCagg, Amy ;
White, Jennifer A. ;
Theroux, Pierre ;
Darius, Harald ;
Lewis, Basil S. ;
Ophuis, Ton Oude ;
Jukema, J. Wouter ;
De Ferrari, Gaetano M. ;
Ruzyllo, Witold ;
De Lucca, Paul ;
Im, KyungAh ;
Bohula, Erin A. ;
Reist, Craig ;
Wiviott, Stephen D. ;
Tershakovec, Andrew M. ;
Musliner, Thomas A. ;
Braunwald, Eugene ;
Califf, Robert M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (25) :2387-2397
[6]   Intensive versus moderate lipid lowering with statins after acute coronary syndromes [J].
Cannon, CP ;
Braunwald, E ;
McCabe, CH ;
Rader, DJ ;
Rouleau, JL ;
Belder, R ;
Joyal, SV ;
Hill, KA ;
Pfeffer, MA ;
Skene, AM .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (15) :1495-1504
[7]  
Collins R, 2002, LANCET, V360, P23, DOI 10.1016/S0140-6736(02)09328-5
[8]   Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes - Phase Z of the A to Z trial [J].
de Lemos, JA ;
Blazing, MA ;
Wiviott, SD ;
Lewis, EF ;
Fox, KAA ;
White, HD ;
Rouleau, JL ;
Pedersen, TR ;
Gardner, LH ;
Mukherjee, R ;
Ramsey, KE ;
Palmisano, J ;
Bilheimer, DW ;
Pfeffer, MA ;
Califf, RM ;
Braunwald, E .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2004, 292 (11) :1307-1316
[9]   Genetic Loci Associated With C-Reactive Protein Levels and Risk of Coronary Heart Disease [J].
Elliott, Paul ;
Chambers, John C. ;
Zhang, Weihua ;
Clarke, Robert ;
Hopewell, Jemma C. ;
Peden, John F. ;
Erdmann, Jeanette ;
Braund, Peter ;
Engert, James C. ;
Bennett, Derrick ;
Coin, Lachlan ;
Ashby, Deborah ;
Tzoulaki, Ioanna ;
Brown, Ian J. ;
Mt-Isa, Shahrul ;
McCarthy, Mark I. ;
Peltonen, Leena ;
Freimer, Nelson B. ;
Farrall, Martin ;
Ruokonen, Aimo ;
Hamsten, Anders ;
Lim, Noha ;
Froguel, Philippe ;
Waterworth, Dawn M. ;
Vollenweider, Peter ;
Waeber, Gerard ;
Jarvelin, Marjo-Riitta ;
Mooser, Vincent ;
Scott, James ;
Hall, Alistair S. ;
Schunkert, Heribert ;
Anand, Sonia S. ;
Collins, Rory ;
Samani, Nilesh J. ;
Watkins, Hugh ;
Kooner, Jaspal S. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2009, 302 (01) :37-48
[10]   Simvastatin inhibits the monocyte expression of proinflammatory cytokines in patients with hypercholesterolemia [J].
Ferro, D ;
Parrotto, S ;
Basili, S ;
Alessandri, C ;
Violi, F .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2000, 36 (02) :427-+