Document Detail


Effects of statin therapy according to plasma high-sensitivity C-reactive protein concentration in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA): a retrospective analysis.
MedLine Citation:
PMID:  19917888     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: We examined whether the antiinflammatory action of statins may be of benefit in heart failure, a state characterized by inflammation in which low cholesterol is associated with worse outcomes.
METHODS AND RESULTS: We compared 10 mg rosuvastatin daily with placebo in patients with ischemic systolic heart failure according to baseline high sensitivity-C reactive protein (hs-CRP) <2.0 mg/L (placebo, n=779; rosuvastatin, n=777) or > or = 2.0 mg/L (placebo, n=1694; rosuvastatin, n=1711). The primary outcome was cardiovascular death, myocardial infarction, or stroke. Baseline low-density lipoprotein was the same, and rosuvastatin reduced low-density lipoprotein by 47% in both hs-CRP groups. Median hs-CRP was 1.10 mg/L in the lower and 5.60 mg/L in the higher hs-CRP group, with higher hs-CRP associated with worse outcomes. The change in hs-CRP with rosuvastatin from baseline to 3 months was -6% in the low hs-CRP group (27% with placebo) and -33.3% in the high hs-CRP group (-11.1% with placebo). In the high hs-CRP group, 548 placebo-treated (14.0 per 100 patient-years of follow-up) and 498 rosuvastatin-treated (12.2 per 100 patient-years of follow-up) patients had a primary end point (hazard ratio of placebo to rosuvastatin, 0.87; 95% confidence interval, 0.77 to 0.98; P=0.024). In the low hs-CRP group, 175 placebo-treated (8.9 per 100 patient-years of follow-up) and 188 rosuvastatin-treated (9.8 per 100 patient-years of follow-up) patients experienced this outcome (hazard ratio, 1.09; 95% confidence interval, 0.89 to 1.34; P>0.2; P for interaction=0.062). The numbers of deaths were as follows: 581 placebo-treated (14.1 per 100 patient-years of follow-up) and 532 rosuvastatin-treated (12.6 per 100 patient-years) patients in the high hs-CRP group (hazard ratio, 0.89; 95% confidence interval, 0.79 to 1.00; P=0.050) and 170 placebo-treated (8.3 per 100 patient-years) and 192 rosuvastatin-treated (9.7 per 100 patient-years) patients in the low hs-CRP group (hazard ratio, 1.17; 95% confidence interval, 0.95 to 1.43; P=0.14; P for interaction=0.026).
CONCLUSIONS: In this retrospective hypothesis-generating study, we found a significant interaction between hs-CRP and the effect of rosuvastatin for most end points whereby rosuvastatin treatment was associated with better outcomes in patients with hs-CRP > or = 2.0 mg/L.
CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00206310.
Authors:
John J V McMurray; John Kjekshus; Lars Gullestad; Peter Dunselman; Ake Hjalmarson; Hans Wedel; Magnus Lindberg; Finn Waagstein; Peer Grande; Jaromir Hradec; Gabriel Kamenský; Jerzy Korewicki; Timo Kuusi; François Mach; Naresh Ranjith; John Wikstrand;
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-16
Journal Detail:
Title:  Circulation     Volume:  120     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-01     Completed Date:  2010-01-05     Revised Date:  2012-09-10    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2188-96     Citation Subset:  AIM; IM    
Affiliation:
British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, UK. j.mcmurray@bio.gla.ac.uk
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00206310
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
C-Reactive Protein / metabolism*
Cholesterol, HDL / blood
Cholesterol, LDL / blood
Female
Fluorobenzenes / therapeutic use*
Heart Failure, Systolic* / blood,  drug therapy,  mortality
Hospitalization / statistics & numerical data
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
Kaplan-Meier Estimate
Male
Multicenter Studies as Topic
Pyrimidines / therapeutic use*
Randomized Controlled Trials as Topic
Retrospective Studies
Risk Factors
Sulfonamides / therapeutic use*
Triglycerides / blood
Chemical
Reg. No./Substance:
0/Cholesterol, HDL; 0/Cholesterol, LDL; 0/Fluorobenzenes; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Pyrimidines; 0/Sulfonamides; 0/Triglycerides; 287714-41-4/rosuvastatin; 9007-41-4/C-Reactive Protein
Investigator
Investigator/Affiliation:
Malin Blideskog / ; Peter Dunselman / ; Ake Hjalmarson / ; John Kjekshus / ; John McMurray / ; Finn Waagstein / ; Hans Wedel / ; Peter Wessman / ; John Wikstrand / ; Eduard Apetrei / ; Vivencio Barrios / ; Michael Böhm / ; John Cleland / ; Jan Cornel / ; Candida Fonseca / ; Assen Goudev / ; Peer Grande / ; Lars Gullestad / ; Jaromir Hradec / ; András Jánosi / ; Gabriel Kamenský / ; Michel Komajda / ; Jerzy Korewicki / ; Timo Kuusi / ; François Mach / ; Vyacheslav Mareev / ; Maria Schaufelberger / ; Johan Vanhaecke / ; Dirk van Veldhuisen / ; Mark Arnold / ; Margrethe Tvedegaard / ; Lubica Cernakova / ; Anne Compagnon / ; Ruth Coy / ; Beatrice Costea / ; Stephanie Detert / ; Judit Farkas / ; Georgi Georgiev / ; Juha Halme / ; Arild Hildebrandt / ; Pernilla Isberg / ; Melanie LaVita / ; Katrin Leichner / ; Katarzyna Milczarek / ; Larisa Plekhova / ; Edel Shaw / ; Arlette Sijbers / ; Philippe Spinewine / ; Lucia Szaboova / ; Nadine Schwarzmann / ; Bengt-Olov Fredlund / ; Mikael Holmberg / ; Katarina Saldeen / ; Ola Samuelsson / ; Karl Swedberg /
Comments/Corrections
Erratum In:
Circulation. 2010 Jun 29;121(25):e461

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