Rosuvastatin for primary prevention in patients with European systematic coronary risk evaluation risk ≥ 5% or Framingham risk >20%: post hoc analyses of the JUPITER trial requested by European health authorities

Abstract

Aims: On the basis of the JUPITER trial, European health authorities recently approved the use of rosuvastatin to reduce first major cardiovascular events among 'high' global risk primary prevention patients defined either by Framingham risk score >20% or European systematic coronary risk evaluation (SCORE) ≥5%. However, as these are post hoc analyses, data describing these subgroups have not previously been available to the clinical community.

Methods and results: We randomized 17 802 apparently healthy men aged ≥50 and women ≥60 with low-density lipoprotein cholesterol (LDL-C) <3.4 mmol/L, who were at an increased vascular risk due to elevated levels of C-reactive protein measured with a high-sensitivity (hs) assay to rosuvastatin 20 mg daily or placebo. Patients with high global cardiovascular risk at baseline were identified by 10-year Framingham risk score >20% or SCORE risk ≥5%. During 1.8-year median follow-up (maximum 5 years) of patients with Framingham risk >20%, the rate of myocardial infarction/stroke/cardiovascular death was 9.4 and 18.2 per 1000 person-years in rosuvastatin and placebo-allocated patients, respectively [hazard ratio (HR): 0.50, 95% confidence interval (CI): 0.27-0.93, P = 0.028]. Among patients with SCORE risk ≥5%, the corresponding rates were 6.9 and 12.0 using a model extrapolating risk for age ≥65 years (HR: 0.57, 95% CI: 0.43-0.78, P = 0.0003) and rates were 5.9 and 12.7 when risk for age was capped at 65 years (HR: 0.47, 95% CI: 0.32-0.68, P < 0.0001).

Conclusion: In primary prevention patients with elevated hs C-reactive protein who have high global cardiovascular risk (10-year Framingham risk score >20% or SCORE risk ≥5%), but LDL-C levels not requiring pharmacologic treatment, rosuvastatin 20 mg significantly reduced major cardiovascular events.

Trial registration: ClinicalTrials.gov NCT00239681.

Figures

Figure 1

Cumulative incidence of myocardial infarction/stroke/cardiovascular death in high-risk patients. The cumulative incidence of myocardial infarction/stroke/cardiovascular death is shown by the treatment group for patients with a 10-year Framingham risk score >20% (upper panel), 10-year systematic coronary risk evaluation risk ≥5% using the extrapolated model (middle panel), and systematic coronary risk evaluation risk ≥5% using the capped model (lower panel). NNT, number needed to treat.

Figure 2

Cumulative incidence of fatal/non-fatal myocardial infarction and stroke in high-risk patients. The cumulative incidence of fatal/non-fatal myocardial infarction and fatal/non-fatal stroke are shown by the treatment group among patients with a 10-year systematic coronary risk evaluation risk ≥5% using the extrapolated (upper panel) and capped models (lower panel).

Figure 3

Effects of rosuvastatin on myocardial infarction/stroke/cardiovascular death in high-risk patients, according to baseline characteristics. The hazard ratios and 95% confidence intervals for rosuvastatin when compared with placebo are shown for patients with Framingham risk score >20% and systematic coronary risk evaluation risk ≥5% (extrapolated and capped models). Size of the point estimate rectangle is proportional to the number of clinical events. The dashed vertical line indicates the relative risk reduction for the entire trial cohort. Also shown are P-values for the test of an interaction between the composite endpoint and categories within each subgroup.