Slowing Atherosclerosis Progression

As an adjunct to diet for your adult patients with hyperlipidemia, CRESTOR® (rosuvastatin calcium) is indicated to slow the progression of atherosclerosis at any stage of the disease.1

The progression of atherosclerosis can be accelerated by LDL-C and impacted by additional risk factors, including2-4

  1. Diabetes
  2. Family history of early CHD
  3. Smoking
  4. Dyslipidemia

5.  Lack of physical activity

6.  Hypertension

7.  High-fat diet

Plaque progression in arteries

For illustration only: Represents potential long-term plaque buildup in the artery.

In this section, you can review results from the METEOR trial, which demonstrated the effectiveness of CRESTOR in slowing the progression of atherosclerosis.

  • Are your hyperlipidemic increased-risk patients at goal?

    In high-risk patients in the ECLIPSE trial, CRESTOR helped more patients achieve LDL-C goal than Lipitor® (atorvastatin calcium).7

    View the data

Address plaque head-on

CRESTOR was proven to slow plaque progression in a 2-year study1,5

In the METEOR trial in patients with hyperlipidemia

Annualized rate of change in maximum CIMT1,5

chart shows the METEOR trial, carotid intima-media thickness (CIMT) increased in the placebo group but did not change in the CRESTOR group

Estimated change in maximum CIMT plotted over 2 years5,6

Change in CIMT over time, CRESTOR vs placebo

In the METEOR trial, carotid intima-media thickness (CIMT) increased in the placebo group but did not change in the CRESTOR group (Figure 1). The rates of change shown in Figure 1 are plotted over time in Figure 2.

Compared to baseline, overall, no significant progression of atherosclerosis was observed with CRESTOR, while significant disease progression was observed with placebo.*1,5

*P<.0001 with placebo.

P=.32 with CRESTOR.

 

  • The most common adverse reactions (%) in the METEOR trial for CRESTOR vs placebo, respectively, were myalgia (12.7 vs 12.1), arthralgia (10.1 vs 7.1), headache (6.4 vs 5.3), dizziness (4.0 vs 2.8), increased CPK (2.6 vs 0.7), abdominal pain (2.4 vs 1.8), and ALT >3x ULN (2.2 vs 0.7)1

  • CRESTOR 40 mg should be used only for those patients not achieving their LDL-C goal with 20 mg

 

TRIAL DESCRIPTION:

Adapted from the METEOR trial.1,5 METEOR was a randomized, double-blind, placebo-controlled trial comparing the effect of CRESTOR 40 mg with placebo on the progression of atherosclerosis over 2 years in 984 low-risk patients (defined as Framingham risk score of <10% over 10 years) with hypercholesterolemia (mean LDL-C of 155 mg/dL) and subclinical atherosclerosis as detected by CIMT for 12 carotid artery sites and assessed via B-mode ultrasound. The primary end point was the annualized rate of change in maximum CIMT for 12 carotid artery sites.

3143524-3097604 Last Updated 7/15

Important Safety Information for CRESTOR Tablets

  • CRESTOR is contraindicated in patients with a known hypersensitivity to any component of this product, in patients with active liver disease, which may include unexplained persistent elevations of hepatic transaminase levels, in women who are pregnant or may become pregnant, and in nursing mothers
  • Cases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with statins, including CRESTOR. These risks can occur at any dose level, but are increased at the highest dose (40 mg)
  • CRESTOR should be prescribed with caution in patients with predisposing factors for myopathy (eg, age ≥65 years, inadequately treated hypothyroidism, renal impairment). The risk of myopathy during treatment with CRESTOR may be increased with concurrent administration of some other lipid-lowering therapies (fibrates or niacin), gemfibrozil, cyclosporine, lopinavir/ritonavir, atazanavir/ritonavir, or simeprevir
  • Therapy with CRESTOR should be discontinued if markedly elevated CK levels occur or myopathy is diagnosed or suspected. There have been rare reports of immune-mediated necrotizing myopathy associated with statin use. All patients should be advised to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever, and if muscle signs and symptoms persist after discontinuing CRESTOR
  • It is recommended that liver enzyme tests be performed before the initiation of CRESTOR and if signs or symptoms of liver injury occur. All patients treated with CRESTOR should be advised to promptly report any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including CRESTOR. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with CRESTOR, promptly interrupt therapy. If an alternate etiology is not found, do not restart CRESTOR
  • CRESTOR should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of chronic liver disease
  • CRESTOR significantly increased INR in patients receiving coumarin anticoagulants. In patients taking coumarin anticoagulants and CRESTOR concomitantly, INR should be determined before starting CRESTOR and frequently enough during early therapy to ensure that no significant alteration of INR occurs
  • Dipstick-positive proteinuria and microscopic hematuria were observed among patients treated with CRESTOR. These findings were more frequent in patients taking CRESTOR 40 mg, though it was generally transient and was not associated with worsening renal function. Although the clinical significance of this finding is unknown, dose reduction should be considered for patients on CRESTOR therapy with unexplained persistent proteinuria and/or hematuria during routine urinalysis testing
  • Increases in HbA1c and fasting serum glucose levels have been reported with statins, including CRESTOR. Based on clinical trial data with CRESTOR, in some instances these increases may exceed the threshold for the diagnosis of diabetes mellitus
  • In the controlled clinical trials database, the most common adverse reactions were headache (3.7%), myalgia (3.1%), abdominal pain (2.6%), asthenia (2.5%), and nausea (2.2%)#,‡‡
  • Rare postmarketing reports of cognitive impairment (eg, memory loss, forgetfulness, amnesia, memory impairment, confusion) have been associated with statin use, including CRESTOR. These reports are generally nonserious and reversible upon statin discontinuation
  • CRESTOR 40 mg should be used only for those patients not achieving their LDL-C goal with 20 mg

Important Safety Information from the JUPITER Study

  • A higher percentage of rosuvastatin-treated patients vs placebo-treated patients (6.6% and 6.2%, respectively) discontinued study medication due to an adverse event, irrespective of treatment causality. Myalgia was the most common adverse reaction that led to treatment discontinuation
  • In JUPITER, there was a significantly higher frequency of diabetes mellitus reported in patients taking rosuvastatin (2.8%) vs patients taking placebo (2.3%). Mean HbA1c was significantly increased by 0.1% in rosuvastatin-treated patients compared to placebo-treated patients. The number of patients with HbA1c >6.5% at the end of the trial was significantly higher in rosuvastatin-treated patients vs placebo-treated patients
  • The most common adverse reactions reported were myalgia (7.6% vs 6.6%), arthralgia (3.8% vs 3.2%), constipation (3.3% vs 3.0%), and nausea (2.4% vs 2.3%) for CRESTOR vs placebo, respectively

Indications

  • CRESTOR is indicated as an adjunct to diet to reduce elevated Total-C, LDL-C, ApoB, non-HDL-C, and triglycerides, and to increase HDL-C in adult patients with primary hyperlipidemia or mixed dyslipidemia, and to slow the progression of atherosclerosis in adult patients as part of a treatment strategy to lower Total-C and LDL-C to target levels
  • CRESTOR is indicated to reduce the risk of myocardial infarction, stroke, and arterial revascularization procedures in patients without clinically evident coronary heart disease but with an increased risk of cardiovascular disease (CVD) based on age (men ≥50 and women ≥60), high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L, and the presence of at least one additional CVD risk factor, such as hypertension, low HDL-C, smoking, or a family history of premature coronary heart disease

Read full Prescribing Information (PDF - 152k) 

#Prescribing Information for CRESTOR. AstraZeneca Pharmaceuticals LP, Wilmington, DE.

‡‡Data on File, 268255, AstraZeneca Pharmaceuticals LP.

References:

  1. Prescribing Information for CRESTOR. AstraZeneca Pharmaceuticals LP, Wilmington, DE.

  2. Naghavi M, Falk E, Hecht HS, et al, for SHAPE Task Force. From vulnerable plaque to vulnerable patient-part III: executive summary of the Screening for Heart Attack Prevention and Education (SHAPE) task force. Am J Cardiol. 2006;98(suppl):2H-15H.
  3. Falk E. Pathogenesis of atherosclerosis. J Am Coll Cardiol. 2006;47(suppl):C7-C12.
  4. Lusis AJ. Atherosclerosis. Nature. 2000;407:233-241.
  5. Crouse JR III, Raichlen JS, Riley WA, et al; METEOR Study Group. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR Trial. JAMA. 2007;297(12):1344-1353.
  6. Data on File, 267039, AstraZeneca Pharmaceuticals LP.
  7. Faergeman O, Hill L, Windler E, et al; on behalf of the ECLIPSE Study Investigators. Efficacy and tolerability of rosuvastatin and atorvastatin when force-titrated in patients with primary hypercholesterolemia. Cardiology. 2008;111(4):219-228.

LIPITOR is a registered trademark of Pfizer Inc.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.