| Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. | |
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MedLine Citation:
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PMID: 19329177 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Statins lower high-sensitivity C-reactive protein (hsCRP) and cholesterol concentrations, and hypothesis generating analyses suggest that clinical outcomes improve in patients given statins who achieve hsCRP concentrations less than 2 mg/L in addition to LDL cholesterol less than 1.8 mmol/L (<70 mg/dL). However, the benefit of lowering both LDL cholesterol and hsCRP after the start of statin therapy is controversial. We prospectively tested this hypothesis. METHODS: In an analysis of 15 548 initially healthy men and women participating in the JUPITER trial (87% of full cohort), we prospectively assessed the effects of rosuvastatin 20 mg versus placebo on rates of non-fatal myocardial infarction, non-fatal stroke, admission for unstable angina, arterial revascularisation, or cardiovascular death (prespecified endpoints) during a maximum follow-up of 5 years (median 1.9 years), according to on-treatment concentrations of LDL cholesterol (>/=1.8 mmol/L or <1.8 mmol/L) and hsCRP (>/=2 mg/L or <2 mg/L). We included all events occurring after randomisation. This trial is registered with ClinicalTrials.gov, number NCT00239681. FINDINGS: Compared with placebo, participants allocated to rosuvastatin who achieved LDL cholesterol less than 1.8 mmol/L had a 55% reduction in vascular events (event rate 1.11 vs 0.51 per 100 person-years; hazard ratio [HR] 0.45, 95% CI 0.34-0.60, p<0.0001), and those achieving hsCRP less than 2 mg/L a 62% reduction (event rate 0.42 per 100 person-years; HR 0.38, 95% CI 0.26-0.56, p<0.0001). Although LDL cholesterol and hsCRP reductions were only weakly correlated in individual patients (r values <0.15), we recorded a 65% reduction in vascular events in participants allocated to rosuvastatin who achieved both LDL cholesterol less than 1.8 mmol/L and hsCRP less than 2 mg/L (event rate 0.38 per 100 person-years; adjusted HR 0.35, 95% CI 0.23-0.54), versus a 33% reduction in those who achieved one or neither target (event rate 0.74 per 100 person-years; HR 0.67, 95% CI 0.52-0.87) (p across treatment groups <0.0001). In participants who achieved LDL cholesterol less than 1.8 mmol/L and hsCRP less than 1 mg/L, we noted a 79% reduction (event rate 0.24 per 100 person-years; HR 0.21, 95% CI 0.09-0.52). Achieved hsCRP concentrations were predictive of event rates irrespective of the lipid endpoint used, including the apolipoprotein B to apolipoprotein AI ratio. INTERPRETATION: For people choosing to start pharmacological prophylaxis, reduction in both LDL cholesterol and hsCRP are indicators of successful treatment with rosuvastatin. |
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Authors:
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Paul M Ridker; Eleanor Danielson; Francisco Ah Fonseca; Jacques Genest; Antonio M Gotto; John Jp Kastelein; Wolfgang Koenig; Peter Libby; Alberto J Lorenzatti; Jean G Macfadyen; B?rge G Nordestgaard; James Shepherd; James T Willerson; Robert J Glynn; |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2009-03-28 |
Journal Detail:
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Title: Lancet Volume: 373 ISSN: 1474-547X ISO Abbreviation: Lancet Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-04-06 Completed Date: 2009-04-17 Revised Date: 2010-06-14 |
Medline Journal Info:
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Nlm Unique ID: 2985213R Medline TA: Lancet Country: England |
Other Details:
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Languages: eng Pagination: 1175-82 Citation Subset: AIM; IM |
Affiliation:
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Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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ClinicalTrials.gov/NCT00239681 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aged Aged, 80 and over C-Reactive Protein / drug effects, metabolism* Cardiovascular Diseases / epidemiology, metabolism, prevention & control* Cholesterol, LDL / blood*, drug effects Disease-Free Survival Double-Blind Method Female Fluorobenzenes / pharmacology, therapeutic use* Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology, therapeutic use* Incidence Male Middle Aged Proportional Hazards Models Prospective Studies Pyrimidines / pharmacology, therapeutic use* Sensitivity and Specificity Statistics, Nonparametric Sulfonamides / pharmacology, therapeutic use* Treatment Outcome |
| Chemical | |
Reg. No./Substance:
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0/Cholesterol, LDL; 0/Fluorobenzenes; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Pyrimidines; 0/Sulfonamides; 287714-41-4/rosuvastatin; 9007-41-4/C-Reactive Protein |
| Comments/Corrections | |
Comment In:
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Curr Cardiol Rep. 2009 Nov;11(6):401-3
[PMID:
19863863
]
Lancet. 2010 Jun 12;375(9731):2071 [PMID: 20494436 ] Lancet. 2009 Apr 4;373(9670):1147-8 [PMID: 19329179 ] Lancet. 2009 Jul 4;374(9683):26; author reply 26-7 [PMID: 19577691 ] Lancet. 2009 Jul 4;374(9683):24-5; author reply 26-7 [PMID: 19577685 ] Lancet. 2009 Jul 4;374(9683):24; author reply 26-7 [PMID: 19577686 ] Lancet. 2009 Jul 4;374(9683):24; author reply 26-7 [PMID: 19577687 ] Lancet. 2009 Jul 4;374(9683):25; author reply 26-7 [PMID: 19577689 ] Lancet. 2009 Jul 4;374(9683):25; author reply 26-7 [PMID: 19577690 ] Lancet. 2009 Jul 4;374(9683):25-6; author reply 26-7 [PMID: 19577688 ] |
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