JUPITER Analysis: Do Statin Benefits Outweigh Diabetes Risk?

JUPITER Analysis: Do Statin Benefits Outweigh Diabetes Risk?
Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012;380(9841):565-571. 

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The Justification for Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial was the first placebo-controlled statin trial to report an increased risk of developing diabetes (Click here to learn more about the JUPITER trial).1 In the current analysis, investigators examined whether the benefits of statin use outweigh the diabetes risk in primary prevention low-risk patients.  

Subjects enrolled in JUPITER (N=17,802) were healthy men and women with no prior CVD event or diabetes, LDL-C <130 mg/dL, and high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L. Participants were randomized to rosuvastatin 20 mg qd or placebo. For the current analysis, subjects were also stratified on the basis of whether they had 0 or ≥1 of the following diabetes risk factors: metabolic syndrome, impaired fasting glucose, body mass index (BMI) ≥30 kg/m2, or A1C >6%.  

The primary endpoint was a composite of myocardial infarction (MI), stroke, unstable angina hospital admission, arterial revascularization, and CV death over 5 years of follow-up. Secondary endpoints were venous thromboembolism (VTE), all-cause mortality, and incident physician-reported diabetes.  

Results:
Subjects with ≥1 risk factor (n=11,508) were more likely to be female, have hypertension, have higher levels of plasma glucose, triglycerides, and A1C, and lower HDL-C levels at baseline compared with study participants with 0 risk factors (n=6,095).
 

Increased diabetes risk was seen among those with ≥1 diabetes risk factor (metabolic syndrome, impaired fasting glucose, A1C >6%, BMI ≥30 kg/m2) at baseline: 1.88 diabetes incidence rate/100 person-years for those with ≥1 diabetes risk factor compared with 0.18 diabetes incidence rate/100 person-years for those with 0 risk factors; hazard ratio (HR), 10.5 (95% confidence interval [CI], 7.0-15.8); P=0.001. 

 Incident diabetes occurred more frequently among rosuvastatin-treated subjects vs those in the placebo group: 270 reports of diabetes vs 216 reports of diabetes, respectively; HR, 1.25 (95% CI, 1.05-1.49); P=0.01.  

The average time to diabetes diagnosis was 84.3 weeks in the rosvastatin group vs 89.7 weeks in the placebo group. Rosuvastatin use accelerated the average time to diabetes diagnosis by 5.4 weeks. Nearly all excess diabetes risk associated with rosuvastatin use occurred in subjects with baseline evidence of impaired fasting glucose. Risk reduction with rosuvastatin treatment:  

≥1 diabetes risk factor 

Endpoint     Risk reduction   HR (95% CI)   P 
Primary endpoint (composite of MI, stroke, hospital admission due to unstable angina, arterial revascularization, CV death)  -39% reduction  0.61 (0.47-0.79)  0.0001  
VTE  -36% reduction    0.64 (0.39-1.06)   0.08  
Total mortality    -17% reduction   0.83 (0.64-1.07)   0.15  
Diabetes  +28% increase    1.28 (1.07-1.54)   0.01  

In absolute terms for study participants with diabetes risk factors, 134 total CV events or deaths were avoided for every 54 new diabetes diagnoses.  

0 diabetes risk factors 

 

Endpoint     Risk reduction   HR (95% CI)   P 
Primary endpoint (composite of MI, stroke, hospital admission due to unstable angina, arterial revascularization, CV death)  -52% reduction  0.48 (0.33-0.68)  0.0001  
VTE  -53% reduction   0.47 (0.21-1.03)   0.05  
Total mortality    -22% reduction   0.78 (0.59-1.03)   0.08  
Diabetes  0% (no increase)    0.99 (0.45-2.21)   0.99 

 

In absolute terms for study participants without diabetes risk factors, 86 total CV events or deaths were avoided with 0 new diabetes diagnoses.  

When CV risk reduction was examined among subjects in JUPITER who developed diabetes (n=486), 18 primary CV events occurred: 8 CV events among rosuvastatin-treated subjects (n=270) and 10 CV events among subjects in the placebo group (n=216). CV risk reduction seen with rosuvastatin treatment (HR, 0.63 [95% CI, 0.25-1.60]) was consistent with CV risk reduction seen across the entire JUPITER trial (HR, 0.56 [95% CI, 0.46-0.69]).  

1. Ridker PM, Danielson E, Fonseca FA, et al; for the JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195-2207.  

Rosuvastatin is not FDA approved for risk reduction of UA hospital admission, CV death, VTE, all-cause mortality, or diabetes 

 

August 2012 

This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.  

Related content:  

JUPITER: Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-reactive Protein  

JUPITER: Design  

JUPITER Analysis: Do Statin Benefits Outweigh Diabetes Risk?  

JUPITER Analysis: Design  

JUPITER Analysis: Baseline Characteristics 0 or ≥1 Major Diabetes Risk Factor  

JUPITER Analysis: Increased Diabetes Risk With ≥1 Risk Factor* at Baseline  

JUPITER Analysis: Incident Diabetes by Treatment Group  

JUPITER Analysis: Average Time to Diabetes Diagnosis  

JUPITER Analysis: Risk Reduction With Rosuvastatin ≥1 Major Diabetes Risk Factor  

JUPITER Analysis: Risk Reduction With Rosuvastatin No Major Diabetes Risk Factor  

JUPITER Analysis: CV Risk Reduction Among Subjects Who Developed Diabetes  

JUPITER Analysis: Conclusions  

 JUPITER Analysis: Limitations  

JUPITER: Statin Therapy for Primary Prevention of Cardiovascular Disease—Rationale  

JUPITER: Statin Therapy for Primary Prevention of Cardiovascular Disease—Participant Profile  

JUPITER: Study Design  

JUPITER Results: Primary Endpoint  

JUPITER Results: Components of Primary Endpoint  

JUPITER: Lipid and Hs-CRP Levels  

JUPITER Results: Summary  

Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials 

Statin Use and Risk for Diabetes: Design 

Statin Use and Risk for Diabetes: Results 

Last Modified: 11/15/2013