September 10, 2009 (Barcelona, Spain) — The use of statin therapy in older adults with normal LDL-cholesterol levels but with systemic inflammation assessed by C-reactive protein (CRP) significantly reduces the risk of cardiovascular morbidity and mortality, much as it does in younger patients, a new study has shown.
The analysis, from Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER), showed that adults >70 years of age had smaller reductions in relative risk compared with those younger than 70 years old but larger absolute reductions, resulting in a lower number needed to treat, particularly for more serious adverse events, according to investigators.
"The trial found a huge benefit, and this is focusing on the 32% of the population who were 70 years old and older at randomization," lead investigator Dr Robert Glynn (Brigham and Women's Hospital, Boston, MA) told heartwire . "Those 32% had 49% of the primary end points, because this is a strongly age-related disease. The really interesting thing about this from the observational studies is that while the effect of cholesterol weakens markedly with age, age is the dominant risk factor for cardiovascular disease."
The results of the study were presented here last week at the European Society of Cardiology 2009 Congress.
Dr Gabriel Steg (Centre Hospitalier Bichat-Claude Bernard, Paris, France), the featured discussant during the clinical-trials-update session, said the analysis confirms the result observed in the overall cohort, but more important, provides solid primary-prevention data in an elderly population, including significant reductions in stroke.
"It provides strong evidence for not depriving elderly patients the benefits of statins," said Steg. Still, despite these new data, Steg said certain caveats applied as JUPITER included specific patients, those with low LDL cholesterol and high CRP levels, leaving an unanswered question about whether the findings can be extended to those without high CRP.
The JUPITER Trial
Reported previously by heartwire , JUPITER is a large, multinational, long-term, double-blind, placebo-controlled, randomized clinical trial that included 17 802 healthy men and women assigned to rosuvastatin (Crestor, AstraZeneca) 20 mg or placebo. The study was designed to assess whether statin therapy should be given to apparently healthy individuals with normal LDL cholesterols but with CRP levels >2.0 mg/dL.
Speaking with heartwire , Glynn, as did Steg during his presentation, noted that the relative risks of elevated cholesterol levels decline with increasing age. For example, said Glynn, a recent meta-analysis showed that an approximate 40-mg/dL reduction in LDL cholesterol in a patient 40 years old with heart disease results in roughly a 56% reduction in risk of cardiovascular events, whereas the same LDL reduction in a patient 70 years old results in only a 17% reduction in risk. The Framingham risk score, he noted, accounts for this interaction with age.
In this JUPITER analysis, researchers showed that rosuvastatin reduced LDL-cholesterol levels to the same extent as among the overall cohort, down to approximately 55 mg/dL. Treatment with rosuvastatin 20 mg in the older cohort reduced the primary end point--a composite of nonfatal MI, nonfatal stroke, revascularization, unstable angina, and cardiovascular death--39% compared with those treated with placebo. There were similar reductions in individual end points, including a 45% reduction in stroke.
JUPITER: Primary and individual end points in patients >70 years old
|End point||Hazard ratio (95% CI)|
|Primary end point (nonfatal MI, nonfatal stroke, revascularization, unstable angina, cardiovascular death)||0.61 (0.46–0.82)|
|Revascularization or unstable angina||0.51 (0.33–0.80)|
|MI, stroke, cardiovascular death||0.61 (0.43–0.86)|
|Any death||0.80 (0.62–1.04)|
|Venous thromboembolism (VTE)||0.59 (0.31–1.11)|
|Primary end point and any death||0.69 (0.56–0.85)|
|Primary end point and any death or VTE||0.69 (0.56–0.84)|
These relative reductions in risk were less than those observed in patients younger than 70 years of age, although the absolute reductions in risk were larger. Given the larger absolute reduction in risk, said Glynn, the number needed to treat for five years to prevent one primary end point was just 19 compared with 29 in younger patients. The number needed to treat to prevent one MI, stroke, or cardiovascular death was 29 compared with 55 in those younger than 70 years.
"We now have evidence that therapy driven by CRP is effective in the elderly, but we don't have any randomized evidence that therapy directed by cholesterol is effective in old people," he told heartwire . "So exactly what the indications are for treatment in this population is a good question at this stage, but I think the results cry out for treating old people for primary prevention."
Primary-prevention studies in older adults are scarce, noted Glynn, pointing out that one of the few studies in elderly patients, the PROSPER study, showed that pravastatin reduced the incidence of vascular disease 15%. Among the 56% of individuals without vascular disease, however, there was only a nonsignificant 6% reduction in risk.
Commenting on the study, Steg pointed out that elderly patients in JUPITER were just 74 years old, on average, so there are still some unknowns about how the very elderly, those older than 80 years of age, would benefit from primary prevention with statins.
AstraZeneca sponsored the JUPITER trial. Glynn has received research support and consulting fees from multiple statin manufacturers, including AstraZeneca. Dr Paul Ridker (Brigham and Women's Hospital, Boston, MA), the lead investigators of the JUPITER study, is a coinventor of patents held by the Brigham and Women's Hospital related to the use inflammatory biomarkers, and these have been licensed to Dade-Behring and AstraZeneca.
Heartwire from Medscape © 2009 Medscape, LLC
Cite this: Elderly Patients in JUPITER Benefit From Statin Therapy - Medscape - Sep 10, 2009.