Transcript Dr. Rahimi February 2012

Laura Mucci, Pharm.D. Candidate
Mercer University 2012
Preceptor: Dr. Rahimi
February 2012
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Limited data available for use of statins for
primary prevention of cardiovascular disease
in older adults
The association between elevated cholesterol
and CV disease weakens with age
 Framingham coronary heart disease risk score for
patients with total cholesterol ≥ 250 mg/dL
 Age 40 years: men 6 points, women 8 points
 Age 75 years: men 1 point, women 2 points
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Age is the dominant risk factor of first
cardiovascular event in people without
diabetes
 Framingham risk score for persons over age 75
▪ Men: 13
▪ Women: 16
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Secondary analysis of the JUPITER trial
 Funded by AstraZeneca, maker of Crestor
 Randomized, double-blind, placebo controlled
trial conducted at 1315 sites in 26 countries
 17,802 total participants
 Analysis focused on participants aged 70 years or
older, which was 5695 participants (32% of total)
 Trial took place between March 2003 – August
2008
 Men age 50 years or older
 Women age 60 years or older
 No prior history of cardiovascular disease or
diabetes
 LDL cholesterol level < 130 mg/dL
 High-sensitivity C-reactive protein level
≥ 2.0 mg/L
 4-week placebo run-in phase to test adherence
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LDL ≥ 130 mg/dL
C-reactive protein level < 2.0 mg/L
Patients with diabetes, prior history of CV
disease, hypothyroid, liver disease,
triglycerides > 500 mg/dL
Lipid lowering therapy within 6 weeks of
randomization
Current use of hormone replacement therapy
Cancer within last 5 years
Poor compliance
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Intervention: participants randomized to 2
groups in a ratio of 1:1
 Crestor (rosuvastatin) 20mg daily
 Placebo
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Follow-up visits at 13 weeks, then 6, 12, 18,
24, 30, 36, 42, 48, 54, and 60 months
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Primary end-point: occurrence of first
cardiovascular event
 Myocardial infarction (non-fatal)
 Stroke (non-fatal)
 Arterial revascularization
 Hospitalization for unstable angina
 Death from cardiovascular causes
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Secondary end-points
 Death from any cause
 Venous thromboembolism
 Incident diabetes
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Safety end-points
 Incident diabetes
 Adverse events
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Endpoints analyzed with the intention-totreat principle
Cox proportional hazards model used to
estimate treatment effects by age group
Likelihood ratio test of age groups by
treatment interaction evaluated possible
heterogeneity in the treatment effect by age
Number needed to treat to prevent 1 event
based on Kaplan-Meier estimates of
cumulative risk at 4 years
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Median LDL cholesterol in the rosuvastatin
group (54 mg/dL) was half that of the placebo
group
Median C-reactive protein in the rosuvastatin
group (2.3 mg/L) was 36% lower than the
placebo group
For all ages, rosuvastatin was associated with
a 44% reduction in the primary endpoint
(95% CI 0.46-0.69, P<0.001)
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32% of trial participants were aged 70 or older
They comprised 49% (194 of 393) of the total
primary cardiovascular endpoints
Absolute reduction in the incidence of
primary endpoints was 0.77 events per 100
person-years
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Number of adults ≥ 70 years needed to treat
for 4 years to prevent 1 primary end point was
24 (95% CI: 15-57)
Number of adults < 70 years needed to treat
for 4 years to prevent 1 primary end point was
36 ( 95% CI: 23-77)
To prevent secondary endpoints: NNT was 17
in those aged ≥ 70 and 27 in those < 70 years
(95% CI: 12-33, 17-57, respectively)
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Clear treatment benefit was seen in older adults
with hypertension and those with a Framingham
risk > 10%
Older participants assigned to placebo had
higher rates of serious adverse events
Older participants in the rosuvastatin group had
higher incidences of muscle weakness, stiffness
or pain, renal disorder, bleeding, GI disorder,
hepatic disorder, and incident diabetes, but
none were statistically significant
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Rosuvastatin substantially reduced the
incidence of major cardiovascular events
Benefits of rosuvastatin emerged shortly
after initiation in older adults
Treatment effects in older adults were
consistent with effects in younger adults, but
absolute event rates and treatment benefits
were greater in older adults
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JUPITER trial differed from previous studies
of statins
 Enrolled older population
 Included stroke in primary endpoints
 Participants had normal LDL levels
 Participants had higher C-reactive protein levels
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Identified a population at risk (high CRP) for
stroke and heart disease who benefit from
statin use despite low LDL levels
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JUPITER also shows a need to include stroke
prevention in evaluations of cost
effectiveness
 Stroke causes a high personal and financial impact
and an increased percentage of total
cardiovascular events with age
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Practitioners often see comorbidities and
proximity to death as barriers to primary
prevention treatment in the older population
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JUPITER shows that benefit emerges quickly
and absolute risk is high in older adults
Fewer older patients need to be treated to
prevent one event
Rosuvastatin was associated with a
significant risk reduction in first CV event
Absolute treatment benefit is greater in older
adults than younger ones
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Large, randomized, blinded, multi-country
trial
Average age of participants was 66 years
Results can be applied to our patients
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Results were extrapolated from study, more
research may be necessary in this population
Funded by Astra-Zeneca, only have evidence
for Crestor
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Glynn RJ, Koenig W, Nordestgaard BG, et al.
Rosuvastatin for primary prevention in older
individuals with high C-reactive protein and
low LDL levels: exploratory analysis of a
randomized trial. Ann Intern Med.
2010;152:488-496.