Journal Article

Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial

Glynn, Robert J, Shepherd, James, Gotto, Antonio M, Kastelein, John JP, Koenig, Wolfgang, Fonseca, Francisco AH, Libby, Peter, Genest, Jacques, Danielson, Eleanor, MacFadyen, Jean G, Willerson, James T, Ridker, Paul M, Nordestgaard, Børge G, Lorenzatti, Alberto J

2009

Overview

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. 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. 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. For people choosing to start pharmacological prophylaxis, reduction in both LDL cholesterol and hsCRP are indicators of successful treatment with rosuvastatin. AstraZeneca.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Aged / Aged, 80 and over / C-Reactive Protein - drug effects / C-Reactive Protein - metabolism / Cardiovascular disease / Cardiovascular Diseases - epidemiology / Cardiovascular Diseases - metabolism / Cardiovascular Diseases - prevention & control / Cholesterol / Cholesterol, LDL - blood / Cholesterol, LDL - drug effects / Clinical outcomes / Data collection / Disease-Free Survival / Double-Blind Method / Female / Fluorobenzenes - pharmacology / Fluorobenzenes - therapeutic use / Heart attacks / Humans / Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology / Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use / Incidence / Internal Medicine / Male / Middle Aged / Myocardial infarction / Prophylaxis / Proportional Hazards Models / Prospective Studies / Pyrimidines - pharmacology / Pyrimidines - therapeutic use / Rosuvastatin Calcium / Sensitivity and Specificity / Statins / Statistics, Nonparametric / Studies / Sulfonamides - pharmacology / Sulfonamides - therapeutic use / Treatment Outcome