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Back: JUPITER Lights Up the Statin Universe

Jeff Unger Picture

 

   Jeff Unger, MD
   PCMG Steering Committee Member
   Charlotte, North Carolina 
   Associate Director for Metabolic Studies
   Catalina Research Institute
   Chino, Californina



The Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin, “JUPITER,” has just been reported in the New England Journal of Medicine (Ridker, et al. NEJM.  2008. 359:2195-2207).  JUPITER evaluated patients having normal LDL-cholesterol levels (< 130 mg/dL), but elevated high-sensitivity c-reactive protein levels (hs-CRP) defined as >2 mg/dL, who took either rosuvastatin (Crestor) 20 mg daily  or placebo. JUPITER was a multinational, double-blind, placebo-controlled, randomized study that included 17,802 healthy men and women assigned to take either rosuvastatin 20 mg daily or placebo. The primary end point of the study—a composite of nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for unstable angina, revascularization and confirmed death from cardiovascular causes—was reduced by 44 % in subjects taking rosuvastatin compared with those on placebo.  


JUPITER was designed as a four year study but was terminated after only 1.9 years based on recommendations from an independent data monitoring board and the JUPITER steering committee. On March 29, 2008, the steering committee reported unequivocal evidence of a reduction in cardiovascular morbidity and mortality among patients treated with rosuvastatin compared with those placed on placebo.


After 1.9 years of follow-up, treatment with rosuvastatin significantly reduced the primary composite end point 44 % compared with placebo. Rosuvastatin patients showed a 48 % reduction in the risk of nonfatal stroke and a 47 % reduction in the risk of MI and death from all cardiovascular causes compared with placebo.


Over 48 months the rosuvastatin subjects lowered their composite LDL-cholesterol from a baseline of
108 mg/dL to 55 mg/dL. The placebo group showed no reduction in their baseline LDL-cholesterol (108mg/dL) over 48 months. Rosuvastatin patients also noted a significant composite reduction in their baseline hs-CRP from 4.2 mg/dL to 1.8 mg/dL vs 4.3 mg/dL to 3.3 mg/dL for placebo.


What can be learned from JUPITER and what questions remain unanswered:

1.      Approximately 50 % of Americans, or 25-30 million people in the US have “normal LDL-cholesterol” values of < 130 mg/dL, yet have hs-CRP > 2 mg/dL. Half of all vascular events occur among patients with these typical lipid and inflammatory marker characteristics. Perhaps aggressive statin therapy may help prevent cardiovascular risk in these individuals.

2.      Do the benefits of rosuvastatin lie in the drug’s ability to significantly lower LDL-cholesterol, hs-CRP, or both? This hypothesis will require testing of agents with targeted vascular anti-inflammatory effects that lack proven beneficial effects on reducing lipids.

3.      How should the hs-CRP be used in clinical practice? In JUPITER, no comparison was made between subjects with and without elevations of hs-CRP, nor were other markers of cardiovascular risk (e.g., cell adhesion molecules, cytokines, pro-atherogenic enzymes) evaluated. The measurement of hs-CRP has been shown to improve the estimation of the risk of acute coronary events.  Perhaps statins not only reduce hs-CRP levels, but those other inflammatory markers as well. JUPITER did NOT address whether patients having a hs-CRP < 2.0 mg/dL would benefit from rosuvastatin therapy.

4.      There is a cost factor that needs to be addressed, as rosuvastatin costs $3.45/d versus considerably lower costs for generic statins (e.g., $.85/d for generic simvastatin). Is there a class effect on reducing hs-CRP and other inflammatory cardiovascular markers?

5.      Who might benefit from JUPITER? Asymptomatic patients who have an intermediate level of risk as estimated on the basis of standard clinical risk markers may benefit. If their LDL-cholesterol levels are < 130 mg/dL hs-CRP levels should be obtained. If the level is > 2.0 mg/dL patients should be started on rosuvastatin 20 mg daily. Lipids and hs-CRP levels should be obtained every 12 months for 4 years. (The target LDL-cholesterol is < 70 mg/dL and the target hs-CRP is < 2 mg/dL). Patients with low cardiovascular risk, normal LDL-cholesterol and hs-CRP levels should probably not be treated with a statin.


Questions for our readers:

1.      Do you normally obtain hs-CRP levels on your asymptomatic patients with normal LDL-cholesterol levels?

2.      Do you plan to switch any of your patients from their current statin therapy to rosuvastatin? If so, why?

3.      What other cardiovascular inflammatory markers are you currently screening for in your intermediate and high risk patient populations?

4.      How are the pharmaceutical representatives in your area for Merck and Pfizer handling the news about JUPITER?

5.      Are any of your patients coming to you and specifically asking you, as their physician, to place them on Crestor, based upon the results of JUPITER?


Visit the PCMG Blog at: http://pcmg2.blogspot.com
to share your thoughts on these questions.


Jeff Unger, MD