Crestor (rosuvastatin calcium) shown to significantly reduce major cardiovascular events

New data from the JUPITER study demonstrated that Crestor (rosuvastatin calcium) 20 mg significantly reduced major cardiovascular (CV) events (defined in this study as the combined risk of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from CV causes) by a dramatic 44% compared to placebo (p<0.001) among men and women with elevated hsCRP but low to normal cholesterol levels.

Results also showed that for patients in the trial taking rosuvastatin: -- the combined risk of heart attack, stroke or CV death was reduced by nearly half (47%, p<0.001). -- risk of heart attack was cut by more than half (54%, p<0.001). -- risk of stroke was cut by nearly half (48%, p=0.002). -- total mortality was significantly reduced by 20% (p=0.02).    

These results were accompanied by a median LDL-C reduction of 50% (p<0.001) resulting in an on-treatment median LDL-C of 55 mg/dL.

On the basis of the data, if the results are projected over a period of 5 years, 25 patients would need to be treated to prevent one major cardiovascular event (NNT=25).

The JUPITER results will be presented today at the American Heart Association Scientific Sessions and were simultaneously published online by the New England Journal of Medicine.

"These results provide new information about Crestor's effects on CV risk. The JUPITER trial confirmed that Crestor dramatically reduces LDL-C cholesterol levels and has now demonstrated a nearly 50% reduction in the risk of heart attack and stroke in a population of patients who had elevated hsCRP but low to normal cholesterol levels," said Howard Hutchinson, Chief Medical Officer for AstraZeneca. "As is appropriate, the medical community, regulators, and guideline committees will now carefully consider these data and any implications for treating patients."

As previously guided, AstraZeneca expects to file a regulatory submission including the JUPITER data in the first half of 2009 and if approved, will begin promotional activities within the approved labeling.

Rosuvastatin is not indicated for the prevention of cardiovascular events. Rosuvastatin should be used according to the prescribing information, which contains recommendations for initiating and titrating therapy according to the individual patient profile. In most countries, the usual recommended starting dose of rosuvastatin is 10 mg.

Rosuvastatin 20 mg was well tolerated in nearly 9,000 patients during the course of the study. There was no difference between treatment groups for major adverse events, including cancer or myopathy. There was a small increase in physician reported diabetes consistent with data from other large placebo controlled statin trials.

JUPITER (Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin) was a long-term, randomized, double-blind, placebo-controlled, large-scale study of 17,802 patients designed to determine if rosuvastatin 20 mg decreases the risk of heart attack, stroke and other major cardiovascular events in patients with low to normal LDL-C but at increased cardiovascular risk as identified by elevated high-sensitivity C-reactive protein (hsCRP) and age. The majority of patients had at least one other risk factor including hypertension, low HDL-C, family history of premature coronary heart disease (CHD) or smoking. hsCRP is a recognized marker of inflammation which is associated with an increased risk of atherosclerotic cardiovascular events.

JUPITER is a part of AstraZeneca's extensive GALAXY clinical trials program, designed to address important unanswered questions in statin research. Currently, more than 69,000 patients have been recruited from 55 countries worldwide to participate in the GALAXY Program.

Studies have previously shown that Crestor was the most effective statin at lowering LDL-C, had a significant effect on raising HDL-C and slowed the progression of atherosclerosis, an underlying cause of cardiovascular disease.

Crestor has now received regulatory approval in over 95 countries. Nearly 15 million patients have been prescribed Crestor worldwide. Data from clinical trials and real world use shows that the safety profile for Crestor is in line with other marketed statins.

Crestor is indicated as an adjunct to diet to reduce elevated Total-C, LDL-C, ApoB, non-HDL-C, and TG levels and to increase HDL-C in patients with primary hyperlipidemia and mixed dyslipidemia. Crestor is also indicated as an adjunct to diet 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 not approved to prevent cardiovascular morbidity and mortality.

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 HMG-CoA reductase inhibitors, 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 greater than or equal to 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, or lopinavir/ritonavir.

Therapy with Crestor should be discontinued if markedly elevated CK levels occur or myopathy is diagnosed or suspected. All patients should be advised to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. It is recommended that liver enzyme tests be performed before and at 12 weeks following both the initiation of therapy and any elevation of dose, and periodically (e.g., semiannually) thereafter. Should an increase in ALT or AST of >3 times ULN persist, reduction of dose or withdrawal of Crestor is recommended. Crestor should be used with caution in patients who consume substantial quantities of alcohol.

Crestor 40 mg should be used only for those patients not achieving their LDL-C goal with 20 mg. Patients initiating Crestor therapy or switching from another statin should begin treatment with Crestor at the appropriate starting dose.

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%).

Please see accompanying full Prescribing Information. If you have any questions concerning Crestor, please contact AstraZeneca at 1-800-237-8898. Crestor is a registered trademark of the AstraZeneca group of companies.