Laura Mucci, Pharm.D. Candidate Mercer University 2012Preceptor: Dr. RahimiFebruary 2012

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

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

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

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

Intervention: participants randomized to 2 groups in a ratio of 1:1 Crestor (rosuvastatin) 20mg daily Placebo

Follow-up visits at 13 weeks, then 6, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months

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

Secondary end-points Death from any cause Venous thromboembolism Incident diabetes

Safety end-points Incident diabetes Adverse events

Endpoints analyzed with the intention-to-treat 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

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)

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

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)

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

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

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 Identified a population at risk (high CRP)

for stroke and heart disease who benefit from statin use despite low LDL levels

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

Practitioners often see comorbidities and proximity to death as barriers to primary prevention treatment in the older population

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

Large, randomized, blinded, multi-country trial

Average age of participants was 66 years

Results can be applied to our patients

Results were extrapolated from study, more research may be necessary in this population

Funded by Astra-Zeneca, only have evidence for Crestor

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.