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Title

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

Authors
McMurray, John J. V.
Kjekshus, John
Gullestad, Lars
Dunselman, Peter
Hjalmarson, Ake
Wedel, Hans
Lindberg, Magnus
Waagstein, Finn
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Published in Circulation. 2009, vol. 120, no. 22, p. 2188-2196
Abstract 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 ≥ 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 ≥ 2.0 mg/L. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00206310.
Keywords AgedAged, 80 and overC-Reactive Protein/*metabolismCholesterol, HDL/bloodCholesterol, LDL/bloodFemaleFluorobenzenes/*therapeutic use*Heart Failure, Systolic/blood/drug therapy/mortalityHospitalization/statistics & numerical dataHumansHydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic useKaplan-Meier EstimateMaleMulticenter Studies as TopicPyrimidines/*therapeutic useRandomized Controlled Trials as TopicRetrospective StudiesRisk FactorsSulfonamides/*therapeutic useTriglycerides/blood
Identifiers
PMID: 19917888
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Research groups Biologie du myocarde (22)
L'athérosclérose et ses complications cliniques (591)
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MCMURRAY, John J. V. et al. 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. In: Circulation, 2009, vol. 120, n° 22, p. 2188-2196. https://archive-ouverte.unige.ch/unige:19949

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Deposited on : 2012-04-23

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