Effects of Statin Therapy According to Plasma High-Sensitivity C-Reactive Protein Concentration in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA)

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) Ͻ2.0 mg/L (placebo, nϭ779; rosuvastatin, nϭ777) or Ն2.0 mg/L (placebo, nϭ1694; rosuvastatin, nϭ1711). 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 Ϫ6% in the low hs-CRP group (27% with placebo) and Ϫ33.3% in the high hs-CRP group (Ϫ11.1% 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 rosuvastatin to placebo, 0.87; 95% confidence interval, 0.77 to 0.98; Pϭ0.024). 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; PϾ0.2; P for interactionϭ0.062). 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; Pϭ0.050) 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; Pϭ0.14; P for interactionϭ0.026). Conclusion-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 Ն2.0 mg/L. Clinical Trial Registration Information-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00206310.

Effects of Statins on Serum Inflammatory Markers: The U.S. National Health and Nutrition Examination Survey 1999-2004

“…It appears that Pravastatin, in addition to having a beneficial effect on the lipid profile, reduces CRP in these patients and has its greatest benefit in patients with the highest CRP levels. These results may imply that inflammation and total cholesterol levels are equally important in atherogenesis 14,24,[26][27][28] . New guidelines from the American Heart Association and the Centers for Disease Control and Prevention (2003) advised doctors to consider testing Americans at moderate risk of heart disease for signs of inflammation in the bloodstream 29) .…”

Atorvastatin modulates constitutive and lipopolysaccharide induced IL-6 secretion in precursors of human skeletal muscle

“…In patients with chronic heart failure, the statins can improve endothelial function by inducing constitutive nitric oxide synthase (cNOS) gene transcription (von Haehling et al, 2003) and reduce CRP levels (Kjekshus et al, 2007). McMurray et al (2009) showed in the CORONA study that treatment with rosuvastatin led to better outcome in a subgroup of patients with elevated CRP. Clinical benefits of statin therapy have also been found in patients with chronic inflammation.…”

Heart Failure After Myocardial Infarction: Clinical Implications and Treatment

“…In fact, 10 mg rosuvastatin daily, in patients with ischemic systolic heart failure, reduced cardiovascular death, myocardial infarction, and stroke mainly in patients with high sensitivity-C reactive protein ≥ 2.0 mg/L. 33 However, further studies are required to recommend routine use of statins in HF after MI. 30 Implantable Cardioverter Defibrillators: Patients with left ventricular dysfunction after myocardial infarction have an increased risk of sudden death due to lethal arrhythmias.…”