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JUPITER: Statine therapie effectief in intermediate-risico, hoog-CRP patiënten

Nieuws - Aug. 25, 2010

JUPITER: Statin therapy effective in intermediate-risk, high-CRP patients


Boston, MA - An analysis of patients in the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial stratified by their underlying level of absolute risk suggests that intermediate-risk patients with elevated C-reactive protein (CRP), including those with a 5% to 10% 10-year risk of cardiovascular disease, benefit from statin therapy. [1]
 

Published online August 24, 2010 in Circulation: Cardiovascular Quality and Outcomes, the JUPITER investigators, led by Dr Paul Ridker (Brigham and Women's Hospital, Boston, MA), show that rosuvastatin (Crestor, AstraZeneca) 20 mg reduced major cardiovascular events among men and women with normal LDL-cholesterol levels, elevated CRP levels, and a 5% to 10% or 10% to 20% 10-year risk of cardiovascular events based on the Framingham and Reynolds risk scores.

To heartwire, Ridker said the data showing the benefits of statin therapy in the JUPITER patients with varying levels of absolute risk provide evidence supporting the 2009 Canadian guidelines recommending the use of CRP to determine statin eligibility among patients considered "intermediate risk." The data, he said, show that the Canadian model "works very well and is a cost-effective, evidence-based approach to primary prevention, an issue of importance as new US guidelines are being considered."


Intermediate-risk patients, not low risk

In this new analysis, Ridker and colleagues assessed the treatment benefit in JUPITER patients with different baseline absolute risks, including those considered low risk, intermediate risk, and high risk. JUPITER, as Ridker has repeatedly pointed out, was not a study of low-risk patients, despite their low baseline LDL-cholesterol levels.  As he told heartwire previously, the event rate in the placebo group was substantially higher than in AFCAPS/TexCAPS, and most patients, more than 13 000, had a 10-year Framingham risk score between 5% and 20%.

In stratifying patients based on underlying risk, treatment with rosuvastatin 20 mg reduced the primary end point—a composite of nonfatal MI, nonfatal stroke, hospitalization for unstable angina, arterial revascularization, or confirmed cardiovascular death—in individuals with a 10-year Framingham risk between 5% and 10% and in those with a 10-year risk between 11% and 20%. Similar reductions were observed when risk was classified using a risk estimate based on the Reynolds risk score.

No benefit was observed in low-risk patients, and none observed in the highest-risk patients when the Framingham risk score was used. Using the Reynolds risk score, however, those at highest risk benefited from statin therapy, a finding that reinforces the utility of CRP, because Reynolds incorporates the biomarker into its risk estimate, said Ridker.
 

JUPITER: Event rates and hazard ratios for the primary end point according to baseline levels of estimated 10-year Framingham and Reynolds risk score

Risk category

Event rate per 100-person years, rosuvastatin 20 mg

Event rate per 100-person years, placebo

Hazard ratio (95% CI)

Framingham 10-year risk
 
     
<5% (n=2791)
0.22
0.34
0.64 (0.23-1.81)
5%-10% (n=6091)
0.50
0.92
0.55 (0.36-0.84)
11%-20% (n=7340)
0.95
1.84
0.51 (0.39-0.68)
>20% (n=1555)
1.72
2.41
0.70 (0.43-1.14)
Reynolds 10-year risk
     
<5% (n=3583)
0.26
0.41
0.62 (0.27-1.43)
5%-10% (n=6436)
0.44
1.00
0.45 (0.29-0.68)
11%-20% (n=5040)
1.07
1.65
0.65 (0.47-0.90)
>20% (n=2651)
1.55
2.84
0.55 (0.38-0.80)

 


Ridker noted that intermediate risk is usually defined as a 10-year Framingham risk of 10% to 20%, and most guidelines adhere to that approach. However, there are a number of men and women who are at increased cardiovascular risk if they have a 5% to 10% Framingham risk and an elevated CRP, he said. Women, he pointed out, have typically been excluded from prior clinical guidelines because they often do not have 10-year Framingham risk scores >10%, much less >20%.
 

"This is important, as JUPITER included nearly 7000 women who had relative benefits of rosuvastatin just as large as that of the men, but almost none of these women would qualify for treatment under current guidelines," said Ridker, citing an analysis reported previously by heartwire.
 

Based on current US guidelines, few intermediate-risk patients with low levels of LDL cholesterol receive statins. Ridker praised the Canadian guidelines, which recommend statins as an adjunctive therapy to lifestyle interventions in those with elevated CRP and a 10-year Framingham risk between 10% and 20%.
 

"My only concern about the Canadian approach is that by not expanding 'intermediate risk' to include those at 5% to 10% risk with elevated CRP, women will still be undertreated," he told heartwire. "That being said, the Canadian approach is a major step in the right direction for having evidence-based and easily followed guidelines. Ironically, right now prevention is simply more aggressive in Canada than in the US, but we have the ability to fix that in the coming year."
 

Above all, however, Ridker stressed that diet, exercise, and smoking cessation form the cornerstone of primary prevention and that statins are not a substitute for good primary care.
 

The JUPITER trial was sponsored by AstraZeneca. Ridker has received grant support and consulting fees from AstraZeneca and is listed as a coinventor on patents held by the Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease and have been licensed to Siemens and AstraZeneca.

Ridker PM, MacFayden JG, Nordestgaard BG, et al. Rosuvastatin for primary prevention among individuals with elevated high-sensitivity C-reactive protein and 5% to 10% and 10% to 20% 10-year risk. Circ Cardiovasc Qual Outcomes 2010; DOI: 10.1161/circoutcomes.110938118.

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