JUPITER ACC March 29, 2009 ndomized Trial of Rosuvastatin in the Preven of Venous Thromboembolism: The JUPITER Trial rt Glynn*, Eleanor Danielson, Francisco Fonseca*, Jacques Gen ntonio Gotto*, John Kastelein*, Wolfgang Koenig*, Peter Libby Alberto Lorenzatti*, Jean MacFadyen, Børge Nordestgaard*, James Shepherd*, James Willerson, and Paul Ridker* on behalf of the JUPITER Trial Study Group An Investigator Initiated Trial Funded by AstraZeneca, USA * These authors have received research grant support and/or consultation fees from one or more statin manufacturers, including Astra-Zeneca. Dr Ridker is a co-inventor on patents held by the Brigham and Women’s Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease that have been licensed to Dade-Behring and AstraZeneca.
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JUPITER ACC March 29, 2009 A Randomized Trial of Rosuvastatin in the Prevention of Venous Thromboembolism: The JUPITER Trial Robert Glynn*, Eleanor Danielson,
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JUPITERACC March 29, 2009
A Randomized Trial of Rosuvastatin in the Preventionof Venous Thromboembolism:
The JUPITER Trial
Robert Glynn*, Eleanor Danielson, Francisco Fonseca*, Jacques Genest*,Antonio Gotto*, John Kastelein*, Wolfgang Koenig*, Peter Libby*,
Alberto Lorenzatti*, Jean MacFadyen, Børge Nordestgaard*, James Shepherd*, James Willerson, and Paul Ridker*
on behalf of the JUPITER Trial Study Group
An Investigator Initiated Trial Funded by AstraZeneca, USA
* These authors have received research grant support and/or consultation fees from one or morestatin manufacturers, including Astra-Zeneca. Dr Ridker is a co-inventor on patents held by the
Brigham and Women’s Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease that have been licensed to Dade-Behring and AstraZeneca.
Presenter Disclosure Information
Robert J Glynn, PhD, ScD; Brigham & Women’s Hospital, Boston, MA
The following relationship exists related to this presentation:
Research Grant AstraZeneca Significant Level
The Brigham & Women’s Hospital holds patents related to the use of inflammatory biomarkers in cardiovascular disease that have been licensed to Dade-Bering and AstraZeneca
JUPITERACC March 29, 2009
JUPITER Timeline
First randomization: March 14, 2003
Last randomization: December 15, 2006
Termination for efficacy: March 30, 2008
Last patient visit: August 20, 2008
Trial results:
Primary end point: November 9, 2008
Pre-specified VTE end point: March 29, 2009
hsCRP and LDL reductions and end points: March 30,
Venous and arterial thrombosis are common, serious, age-related events that often co-occur and share some risk factors
Controversies persist regarding the nature and extent of their shared pathways and whether treatments of demonstrated efficacy for one condition have consistent benefits for the primary or secondary prevention of the other
Benefits of statins might accrue not only through effects on lipids but also through influence on thrombosis and inflammation. Specifically, statins downregulate the blood coagulation cascade through decreased tissue factor expression, which leads to reduced thrombin formation*
Observational Evidence: In non-randomized cohort and case-control studies and registries, statins have often, but not always, been associated with reduced risk of VTE.
These studies cannot exclude indication bias. Many included prevalent statin users, and poor health affects the decision to initiate and persist in therapy. They also did not consider the possibility that the reduction in VTE events is secondary to a statin-induced reduction in arterial hospitalizations.
Similar evidence from observational studies indicated benefits for statins on mortality in heart failure, but trials (CORONA, GISSI) refuted this hypothesis
Clear need for a prospective randomized trial
JUPITERInclusion and Exclusion Criteria, Study Flow
89,863 Screened
17,802 Randomized
8,901 Assigned to Rosuvastatin 20 mg
8,901 Assigned toPlacebo
Reason for Exclusion (%)
LDL-C > 130 mg/dL 53hsCRP < 2.0 mg/L 37Withdrew Consent 4Diabetes 1Hypothyroid <1Liver Disease <1TG > 500 mg/dL <1Age out of range <1Current Use of HRT <1Cancer <1Poor Compliance/Other 3
8,600 Completed Study120 Lost to follow-up
8,600 Completed Study120 Lost to follow-up
8,901 Included in Efficacy and Safety Analyses
8,901 Included in Efficacy and Safety Analyses
89,890 Screened
Men > 50 yearsWomen > 60 yearsNo CVD, No DMLDL < 130 mg/dLhsCRP > 2 mg/L
17,802 Randomized
Reason for Exclusion (%)
LDL > 130 mg/dL 52hsCRP < 2.0 mg/L 36Withdrew Consent 5Diabetes 1Hypothyroid <1Liver Disease <1TG > 500 mg/dL <1Age out of range <1Current Use of HRT <1Cancer <1Poor Compliance/Other 3
4 weekPlaceboRun-In
8,857 Completed Study44 Lost to follow-up
8,901 Assigned to Rosuvastatin 20 mg
8,901 Assigned toPlacebo
8,864 Completed Study37 Lost to follow-up
8,901 Included in Efficacy and Safety Analyses
8,901 Included in Efficacy and Safety Analyses
Ridker et al NEJM 2008
JUPITERSymptomatic VTE
Symptomatic venous thromboembolism was a pre-specified secondary end point
Upon identification of a new VTE case, site investigators indicated the source of confirmation (venous ultrasonogram or venogram for DVT; angiogram, CT scan, or ventilation-perfusion scan for PE)
Initiation and indication for anticoagulation therapy also noted
Unprovoked VTE: no trauma, hospitalization, or surgery within 3 months before diagnosis, and no malignancy diagnosed before or up to 3 months after the VTE
Unprovoked and provoked VTE, pulmonary embolism and deep vein thrombosis alone were tertiary end points.
JUPITERVTE analysis
Primary efficacy analyses counted all events diagnosed by March 30, 2008 according to the intention to treat principle
Safety analyses also included additional events before the closeout visit and unblinding
Competing risks analyses compared effects of rosuvastatin on first VTE versus first primary cardiovascular event
Estimates of net clinical benefits considered the impact on the number needed to treat (NNT) of inclusion of VTE in a composite with the primary cardiovascular event, and also with total mortality
JUPITERBaseline Clinical Characteristics
Rosuvastatin Placebo(N = 8901) (n = 8901)
Age, years (IQR) 66 (60-71) 66 (60-71) Female, N (%) 3,426 (38) 3,375 (38)Ethnicity, N (%) Caucasian 6,358 (71) 6,325 (71) Black 1,100 (12) 1,124 (13) Hispanic 1,121 (13) 1,140 (13)Body mass index ≥ 30 kg/m2, N (%) 3,338 (38) 3,336 (38)Waist circumference (cm) ≥100 (men), ≥95 (women), N (%) 4,503 (51) 4,546 (52)Smoker, N (%) 1,400 (16) 1,420 (16)Metabolic Syndrome, N (%) 3,652 (41) 3,723 (42)hsCRP≥5 mg/L, N (%) 3,618 (41) 3,726 (42)LDL>100 mg/dL, N (%) 5,781 (65) 5,747 (65)HDL<40 (men), <50 (women), N (%) 2,833 (32) 2,856 (32)
All values are median (interquartile range) or N (%)