Phase III Results Show CRESTOR Has Best-in-Class Potential

New statin demonstrates a dramatic impact on lipid levels, ability to get patients to target cholesterol levels and excellent tolerability ^1,2,3

American College of Cardiology (ACC), Orlando, Florida (March 20, 2001) – Today at ACC, researchers presented the eagerly anticipated Phase III clinical trial results for CRESTOR (rosuvastatin - previously known as ZD4522), AstraZeneca’s new statin. The data show that CRESTOR is superior to the most widely prescribed statins including atorvastatin in terms of lowering LDL cholesterol (often referred to as "bad" cholesterol) and getting more patients to their target lipid levels. It also raises HDL cholesterol (often referred to as "good" cholesterol) significantly more than atorvastatin.

"Heart disease and stroke remain the leading causes of hospitalization and death for both men and women in Canada," says Dr. Lawrence Leiter, Head, Division of Endocrinology and Metabolism, St. Michael’s Hospital, Toronto, Ontario. "Too many Canadians continue to have unacceptably high levels of cholesterol, despite the fact that we know hypercholesterolemia is a major risk factor for cardiovascular disease. The aggressive LDL reductions that can be achieved with drugs like CRESTOR should certainly help bring more patients’ cholesterol to optimal levels."

Superior Efficacy

Data from two head-to-head comparative trials involving over 1,000 patients show a significantly better reduction in LDL cholesterol (a major marker for the development of cardiovascular disease) with CRESTOR, compared to other widely prescribed statins.^1,2 In one study, LDL cholesterol was reduced by 49 per cent with CRESTOR 10 mg compared to 37 per cent with simvastatin 20 mg and 28 per cent with pravastatin 20 mg.² In another study, CRESTOR 10 mg reduced LDL cholesterol by 43 per cent compared to a 35 per cent reduction with atorvastatin 10mg.¹

In addition to LDL cholesterol lowering, CRESTOR 10 mg produced a significantly greater increase in HDL cholesterol compared with atorvastatin 10 mg (12 per cent versus 8 per cent, respectively) and a similar increase compared to simvastatin and pravastatin.^1,2 Triglyceride levels were effectively reduced to the same extent by all the statins. All studies also show that CRESTOR is safe and well tolerated, similar to other statins.^1,2,3

Greater numbers of patients reach target cholesterol levels within guidelines

"A number of recent Canadian research studies have demonstrated that the majority of Canadian patients fail to achieve their LDL cholesterol goals," says Dr. Leiter. "In the studies reported today, a greater proportion of patients treated with rosuvastatin reached their LDL target relative to those treated with comparative statins."

In the comparative trial versus pravastatin and simvastatin, 91 per cent of medium-risk patients attained target LDL-cholesterol goals (as defined by the U.S. National Cholesterol Education Program Expert Panel⁴) with CRESTOR 10 mg compared to 45 per cent of similar patients achieving goal with pravastatin 20 mg, and 68 per cent with simvastatin 20 mg. In the high-risk category, 67 per cent of patients achieved target levels with CRESTOR 10 mg versus only seven per cent with pravastatin 20 mg and 19 per cent with simvastatin 20 mg.²

Similar findings were observed in the comparative trial with atorvastatin. Eighty-seven per cent of medium-risk patients attained target LDL cholesterol goals (as defined by the National Cholesterol Education Program Expert Panel⁴) with CRESTOR 10 mg compared with 72 per cent of similar patients with atorvastatin 10 mg. In the high-risk category, 47 per cent of patients achieved target levels with CRESTOR 10 mg versus only 19 per cent with atorvastatin 10 mg.¹

"These findings are crucial because the majority of patients are initiated and remain on a statin at the lowest available dose, which is why so many currently fail to reach their goal. It is therefore logical to give patients the most effective statin," states Dr. Michael Davidson, President of the Chicago Center for Clinical Research, and Principal Investigator for the study that compared CRESTOR to atorvastatin.

CRESTOR also demonstrated superior efficacy in a trial involving patients with heterozygous familial hypercholesterolemia, which is an inherited disorder characterized by very high levels of cholesterol and can result in premature coronary heart disease and death at a young age. The incidence of this condition is 1 in 500 in the general population, however, in Quebec the incidence is two to three times higher. ⁵

In the trial that involved over 600 patients treated for 18 weeks, CRESTOR 20 mg to 80 mg/day reduced LDL cholesterol by 58 per cent versus 50 per cent with atorvastatin.³ Treatment with CRESTOR also resulted in 24 per cent of patients achieving NCEP target LDL cholesterol goals compared with three per cent with atorvastatin. In addition, CRESTOR increased HDL cholesterol to a significantly greater level than did atorvastatin.³

"These data confirm results from the other two studies showing that CRESTOR brings more patients in all risk categories, to target cholesterol levels, than existing therapies," concludes Dr. Evan Stein, Principal Investigator and President Medical Research Laboratories, Kentucky.

"CRESTOR will provide a tremendous additional weapon in the global fight against coronary heart disease," observes Philip Barter, Professor of Cardiology at the Royal Adelaide Hospital in Australia.

About AstraZeneca Canada Inc.

AstraZeneca is one of the world’s leading pharmaceutical companies with a formidable product portfolio spanning seven major therapeutic areas: cardiovascular, gastrointestinal, oncology, pain control, respiratory, central nervous system and infection. AstraZeneca’s brands include Zomig^®, Accolate^®, Arimidex^®, Atacand^®, Losec^®, Xylocaine^®, Zestril^®, Diprivan^®, and Pulmicort^®. The Canadian headquarters and manufacturing facilities of AstraZeneca Canada Inc. are located in Mississauga, Ontario, with a state-of-the art research centre based in Montreal, Quebec.

Reference:

1. Davidson M et al. ZD4522 is superior to atorvastatin in decreasing low density lipoprotein cholesterol and increasing high density lipoprotein cholesterol in patients with type IIa or Ilb hypercholesterolemia. 50th Annual Scientific Session of the American College of Cardiology, March 2001.
2. Paoletti R et al. ZD4522 is superior to pravastatin and simvastatin in reducing low-density lipoprotein cholesterol, enabling more hypercholesterolemic patients to achieve target low-density lipoprotein cholesterol guidelines. 50th Annual Scientific Session of the American College of Cardiology, March 2001.
3. Stein E et al. ZD4522 is superior to atorvastatin in the treatment of patients with heterozygous familial hypercholesterolemia. 50th Annual Scientific Session of the American College of Cardiology, March 2001.
4. Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. The Expert Panel. Archives of Internal Med 1988;148:36-69
5. Gagne C, Moorjani S, Brun D, Touissant M, Lupien PJ. Heterozygous familial hypercholesterolemia. Atherosclerosis 1979;34:13-24