JUPITEROVMC LANDMARK TRIALS SERIES

Ridker PM, et al. "Rosuvastatin to prevent vascular events in men and women with elevated C-reactive

protein". The New England Journal of Medicine. 2008. 359(21):2195-2207.

The Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin

(JUPITER)

BACKGROUND High level of inflammatory biomarker C-

reactive protein can predict future vascular events

Statins lower levels of CRP as well as cholesterol

Sometimes cardiovascular events can still occur in patients with normal LDL cholesterol

The JUPITER trial seeks to assess if statin can benefit patients without hyperlipidemia but with elevated CRP levels

CLINICAL QUESTION

In patients with normal LDL and elevated high-sensitivity CRP (HS-CRP), does

rosuvastatin reduce the incidence of major CV events?

DESIGN

Analysis: Intention-to-treat Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial N=17,802 patients with normal LDL and elevated HS-CRP

Rosuvastatin (n=8,901) Placebo (n=8,901)

Setting: 1315 centers in 26 countries Enrollment: 2003-2006 Median follow-up: 1.9 years Primary outcome: Combined endpoint of first major CV event

POPULATION

Inclusion Criteria Men >50 years, or women >60 years LDL <130 mg/dL HS-CRP >2.0 mg/L Triglycerides <500 mg/dL No history of CV disease

Exclusion Criteria Patients who have used any lipid-

lowering Post-menopausal hormone replacement

therapy Diabetes SBP >190 mmHg or DBP >100 mmHg Cancer (except basal or squamous cell

carcinoma of the skin) in the prior 5 years

Recent alcohol or drug abuse Inflammatory conditions (including, but

not limited to, severe arthritis, lupus, IBD)

Use of immunosuppressants

INTERVENTIONS

Randomization: Rosuvastatin 20mg qday Placebo

Four-week placebo-only run-in phase; those who took more than 80% of their tablets were enrolled in the trial

Follow-up visits were scheduled at 13 weeks then every 6 months after randomization until month 60

Some sites performed telephone follow-ups with patient between inperson visits Patients followed up in a close-out visit following cessation of the study

CRITICISMS

Many patients were not on optimal medical therapy for their risk factors (eg, aspirin therapy if high Framingham score)

Trial was truncated at 2 years so possible overestimation of treatment effect Did not include Asian participants, important because this group has distinct

rosuvastatin pharmacokinetics Individuals with normal HS-CRP values (eg, <2 g/L) were not studied Did not adequately address increased risk of new-onset DM

BOTTOM LINE

Rosuvastatin significantly reduces the incidence of major CV events (eg death, MI, stroke) in patients without hyperlipidemia but

elevated high sensitivity CRP.

DISCUSSION QUESTIONS

What did the JUPITER trial suggest about CRP levels and statin use?

According to the JUPITER trial, should patients without hyperlipidemia be treated with statin?

When studying rosuvastatin, why is it recommended to have Asian participants?

DISCUSSION QUESTIONS/ANSWERS

What did the JUPITER trial suggest about hsCRP levels and statin use? ANSWER: There is a strong linear association with elevated hsCRP and ischemic stroke/vascular

mortality. In patients with elevated CRP levels at an increased risk of cardiovascular events, a statin is recommended because statins lower hsCRP level.

According to the JUPITER trial, should patients without hyperlipidemia be treated with statin? ANSWER: In a patient with normal LDL level but elevated high sensitivity CRP with increased risk of

CV events, a statin is recommended When studying rosuvastatin, why is it recommended to have Asian participants?

ANSWER: Asian participants processs Rosuvastatin therapy differently. They are at increased risk of side effects, especially myopathy may be increased. Therefore, half the standard dose may be recommended.

BOARD-LIKE QUESTION

61 yo man is evaluated for annual exam and asks for advise on cardiac risk assessment. He denies any current chest pain, SOB, PND, orthopnea. He runs 4 miles ever 3 days and has never smoked. He has no medical problems and does not take any medications.Cardiovascular risk calculation using Pooled Cohort question is 7% risk of MI or CV event within 10 years.

ADAPTED from MKSAP 17

QUESTIONWhat test should be performed on this patient? A. Cardiac CT angiographyB. Cardiac CathC. Fractionated lipoprotein profileD. High sensitivity CRPE. Stress Echo

BOARD-LIKE QUESTION

Educational Objective: High-sensitivity C-reactive (hsCRP) protein level can guide treatment and cardiac risk stratification in a patient at intermediate risk of cardiovascular disease.

Key Point:- Patients with hsCRP>1 are considered

high risk- hsCRP<1 is considered low risk- There is no role in evaluating lipid

particle size and number for targeting treatment regimen

ANSWERWhat test should be performed on this patient? A. Cardiac CT angiographyB. Cardiac CathC. Fractionated lipoprotein profileD. High sensitivity CRPE. Stress Echo