TY - JOUR
T1 - Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin
T2 - a prospective study of the JUPITER trial
AU - Ridker, Paul M.
AU - Danielson, Eleanor
AU - Fonseca, Francisco AH
AU - Genest, Jacques
AU - Gotto, Antonio M.
AU - Kastelein, John JP
AU - Koenig, Wolfgang
AU - Libby, Peter
AU - Lorenzatti, Alberto J.
AU - MacFadyen, Jean G.
AU - Nordestgaard, Børge G.
AU - Shepherd, James
AU - Willerson, James T.
AU - Glynn, Robert J.
PY - 2009
Y1 - 2009
N2 - 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. Funding: AstraZeneca.
AB - 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. Funding: AstraZeneca.
UR - http://www.scopus.com/inward/record.url?scp=63649095045&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=63649095045&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(09)60447-5
DO - 10.1016/S0140-6736(09)60447-5
M3 - Article
C2 - 19329177
AN - SCOPUS:63649095045
VL - 373
SP - 1175
EP - 1182
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 9670
ER -