JUPITER: Hoog-risico patiënten hebben baat bij rosuvastatine
JUPITER: High-risk patients benefit from rosuvastatin
November 9, 2010
Eur Heart J 2010; DOI: 10.1093/eurheartj/ehq370.
Treating high-risk primary-prevention patients with LDL-cholesterol levels not reaching the conventional threshold for pharmacologic intervention with rosuvastatin (Crestor, AstraZeneca) results in a significant reduction in the risk of MI, stroke, or cardiovascular death, according to the results of a new study.
The data, a post hoc subgroup analysis from Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER), was requested by the European health authorities and provides support for their modest extension of the rosuvastatin label to primary-prevention patients with low LDL-cholesterol levels but who are considered high risk based on other risk factors.
Published online October 22, 2010 in the European Heart Journal by Dr Wolfgang Koenig (University of Ulm Medical Center, Germany) and Dr Paul Ridker (Brigham and Women's Hospital, Boston), the data showed that patients with a 10-year Framingham risk score >20% or an estimated Systematic Coronary Risk Evaluation (SCORE) risk >5% had statistically significant reductions, 50% and 43%, respectively, in the risk of MI, stroke, or cardiovascular death when treated with rosuvastatin compared with patients treated with placebo.
Koenig said that the European decision differs from the US Food and Drug Administration (FDA) approval made earlier this year. The FDA approved rosuvastatin for reducing the risk of stroke, MI, and revascularization procedures in individuals who have normal LDL levels and no clinically evident coronary heart disease but who do have an increased risk based on age, CRP levels, and the presence of at least one additional CVD risk factor.
"The FDA approval was based on the JUPITER trial taking into account CRP and one additional risk factor," said Koenig. "The European Medicines Agency [EMA] does not take into account elevated CRP levels but just focused on patients who are at high risk based on the available risk scores. From a scientific viewpoint, it's a bit difficult to understand their decision, but by and large what this new analysis tells us is that we see the same results in the high-risk patients as we saw in the overall trial."
Recently, the European health authorities endorsed the use of rosuvastatin in patients with a Framingham risk score >20% or a SCORE risk >5%. The purpose of the latest analysis, explained Koenig, was to provide European doctors with data from JUPITER on the highest-risk patients included in the trial.
Overall, 1558 were considered high risk by having a 10-year Framingham risk score >20%, and 9302 were considered high risk with a SCORE risk >5%. As the SCORE model is designed to assess risk in patients 45 to 64 years of old, the researchers also analyzed the reduction in cardiovascular risk among patients younger than 65 years old with a SCORE risk >5%.
Consistent with the results of the overall trial, there was a significant reduction in the composite end point of MI, stroke, and cardiovascular death among high-risk patients treated with rosuvastatin. The reduction in risk was observed among patients classified high risk by the Framingham and SCORE risk models and was also observed in SCORE patients younger than 65 years old. In terms of the primary end point, there was a trend toward reduced risk in patients considered high risk based on their Framingham risk score, but a significant 39% reduction in risk among patients with SCORE risk >5% and a 44% reduction in risk among SCORE patients younger than 65 years old.
As reported previously the European decision does not accurately represent the patients included in JUPITER. The JUPITER trial included 7340 patients with a Framingham risk score of 11% to 20% and 6091 patients with a Framingham risk score of 5% to 10%, a low- to intermediate-risk cohort. These patients fall outside the European indication for rosuvastatin in the primary-prevention setting but had "substantive absolute-risk and large relative-risk reductions when treated with rosuvastatin," write Koenig and Ridker in the journal.
Koenig called the EMA decision a compromise between scientific evidence and economics, and the primary-prevention label extension of rosuvastatin to only high-risk patients was selected arbitrarily. He noted that the European risk-assessment models do not include high-sensitivity C-reactive protein (hs-CRP), so the agency felt it was unable to make recommendations based on CRP levels.
New Canadian lipid guidelines now recommend the testing of hs-CRP in select patients to help inform treatment decisions. The change came on the heels of JUPITER and recommends that clinicians test for hs-CRP in patients at intermediate risk for cardiovascular events.