JUPITER: Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluatin

1
JUPITER Justification for the Use of statins in
Primary prevention an Intervention Trial
Evaluating Rosuvastatin

• Purpose
• To evaluate whether people with low to normal
  levels of low-density lipoprotein cholesterol
  (LDL-C) and elevated levels of high-sensitivity
  C-reactive protein (hsCRP) would benefit from
  statin (rosuvastatin) treatment in terms of
  reducing major cardiovascular events.
• Reference
• Ridker PM, Danielson E, Fonseca FAH 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
  200835921952207.

2
JUPITER Justification for the Use of statins in
Primary prevention an Intervention Trial
Evaluating Rosuvastatin - TRIAL DESIGN -

• Design
• Multicenter, multinational, randomized,
  double-blind, placebo-controlled trial.
• Patients
• 17,802 individuals with LDL-C levels of lt130
  mg/dL (3.4 mmol/L) and hsCRP levels of 2.0 mg/L.
  Individuals with a history of cardiovascular
  disease were excluded, as were those who had
  previously used lipid-lowering drugs.
• Follow-up and primary endpoint
• Combined primary endpoint of non-fatal
  myocardial infarction, non-fatal stroke, arterial
  revascularization, hospitalization for unstable
  angina, or death from cardiovascular causes.
• Treatment
• Rosuvastatin 20 mg daily or placebo.

3
JUPITER Justification for the Use of statins in
Primary prevention an Intervention Trial
Evaluating Rosuvastatin - TRIAL DESIGN continued
-

Baseline characteristics
Rosuvastatin
Placebo
(n8901)
(n8901)
Median age (years)
66
66
Female sex ()
39
38
Body mass index - median
28
28
hsCRP(mg/L) - median
4.2
4.3
Median lipid values mg/dL (mmol/L)
Total cholesterol
186
(4.8)
185
(4.8)
LDL cholesterol
108
(2.8)
108
(2.8)
HDL cholesterol
49
(1.3)
49
(1.3)
Triglycerides
118
(1.3)
118
(1.3)
Metabolic syndrome ()
41
42
Ridker et al. N Eng J Med 200835921952207.
4
JUPITER Justification for the Use of statins in
Primary prevention an Intervention Trial
Evaluating Rosuvastatin - RESULTS -

• Primary endpoint and follow-up
• Upon the recommendations of an independent
  data-monitoring committee and the JUPITER
  steering committee, the trial was stopped
  prematurely after a median follow-up of 1.9 years
  (maximum of 5 years). At this point, there had
  been a significant reduction in the combined
  primary endpoint of major cardiovascular events
  among patients who had received rosuvastatin in
  comparison with those who had received placebo.
• Other endpoints
• There were significant reductions in the
  following outcomes
• Fatal or non-fatal myocardial infarction
• Fatal or non-fatal stroke
• Arterial revascularization or unstable angina
• Myocardial infarction, stroke or CV death
• All-cause mortality
• Other results
• Rosuvastatin showed consistent benefit in all
  subgroups, according to age, race or ethnic
  group, region of origin, risk factor status and
  Framingham risk score, and it showed the first
  demonstrated benefit in women without established
  CHD. Relative risk reductions in the rosuvastatin
  group were similar for women (46) and men (42).
  The number of serious adverse events was similar
  between the two groups.
• There was no difference between treatment groups
  for muscle weakness, cancer, hematological
  disorders, gastrointestinal, hepatic or renal
  systems. However, there was a small but
  significant increase in investigator-reported
  diabetes in patients treated with rosuvastatin.

5
JUPITER Justification for the Use of statins in
Primary prevention an Intervention Trial
Evaluating Rosuvastatin - RESULTS -

Primary endpoint and composite endpoints
Placebo
Rosuvastatin
Hazard ratio
(n8901)
(n8901)
p value
(95 CI)
(n)
(n)
Primary endpoint
Major cardiovascular events
251
142
0.56 (0.460.69)
lt0.00001
Other endpoints
Any myocardial infarction
68
31
0.46 (0.300.70)
0.0002




Any stroke
64
33
0.52 (0.340.79)
0.002
Arterial revascularization orhospitalization for
unstable angina
143
76
0.53 (0.400.70)
lt0.00001
Hospitalization for unstable angina
27
16
0.59 (0.321.10)
0.09




Death from CV causes
157
83
0.53 (0.400.69)
lt0.00001
All-cause mortality
247
198
0.80 (0.670.97)
0.02
Ridker et al. N Eng J Med 200835921952207.
6
JUPITER Justification for the Use of statins in
Primary prevention an Intervention Trial
Evaluating Rosuvastatin - RESULTS continued -
No. at risk Rosuvastatin Placebo
Ridker et al. N Eng J Med 200835921952207.
7
JUPITER Justification for the Use of statins in
Primary prevention an Intervention Trial
Evaluating Rosuvastatin - RESULTS continued -

Rosuvastatin better
30.0
Ridker et al. N Eng J Med 200835921952207.
8
JUPITER Justification for the Use of statins in
Primary prevention an Intervention Trial
Evaluating Rosuvastatin - SUMMARY -

• In individuals with low to normal levels of
  LDL-C and elevated levels of hsCRP, treatment
  with rosuvastatin significantly reduced the
  primary endpoint of major cardiovascular events.
• There was a 44 reduction in the primary
  endpoint of major cardiovascular events (a
  composite of CV death, MI, stroke, unstable
  angina, arterial revascularisation) in patients
  who received rosuvastatin 20 mg compared with
  those who received placebo (plt0.00001).
• A 20 reduction in total mortality was observed
  in patients who received rosuvastatin 20 mg
  compared with placebo (p0.02).
• The number needed to treat with rosuvastatin for
  two years to prevent one primary endpoint is 95.
• Although there was no difference between
  treatment groups for muscle weakness, cancer,
  hematological disorders, gastrointestinal,
  hepatic or renal systems, there was a higher
  incidence of physician-reported diabetes in
  rosuvastatin treated patients.