Clinically significant, rapid reductions in plasma low-density lipoprotein (LDL-C), as well as increases in high-density lipoprotein (HDL-C), were seen when patients with mild to moderate hypercholesterolaemia were treated with ZD4522. At six weeks, the average reduction in LDL-C was greater than 50% in patients receiving a once daily 10 mg dose of ZD4522, and 65% in patients receiving a daily dose of 80mg. This surpasses the maximal reductions previously reported for all other statins when used as monotherapy  [2]. Furthermore, approximately 90% of LDL-C reduction occurred within the first two weeks of treatment with ZD4522, indicating that ZD4522 has a rapid onset of efficacy.

"The improvement in lipid profiles of patients treated with ZD4522 shows real promise," said Professor Anders Olsson, trial principal investigator. "The data for this new statin are revealing that it has the potential to be superior to currently available statins and thus to offer a valuable addition to the fight against coronary heart disease."

Elevated LDL-C is one of the most significant contributory factors to atherosclerosis, which is a common cause of cardiovascular disease, the world's leading cause of death  [3].

Statins are the first line treatment for patients with elevated LDL-C. However, despite significant therapeutic advances, there remains a need for more aggressive LDL-C lowering which would enable more patients to reach their target LDL-C levels, (as recommended in international guidelines for the treatment of hypercholesterolaemia.  [4],  [5]) - in many cases, without requiring titration from the initial start-dose. Efficacy such as that demonstrated by ZD4522, may help to achieve this.

Over 6 weeks, all doses (1, 2.5, 5, 10, 20, 40, 80mg) of ZD4522 produced statistically significant greater reductions in LDL-C compared with placebo, as well as demonstrating improvements in other important lipid parameters, including a reduction in triglycerides (TG) - 10-35% - and an increase in HDL-C - 9-14%

Some patients were randomised to receive open-label atorvastatin to benchmark the responses of the trial population, but no statistical comparisons were made between ZD4522 and atorvastatin. Data from direct statistical comparisons between ZD4522 and currently available statins will be available from the Phase III programme.

The safety profile of ZD4522 was comparable to that of atorvastatin and of placebo. Over the six week treatment period, ZD4522 was well tolerated across all doses up to 80 mg/day. The adverse events most commonly reported during treatment with ZD4522 (not related to dose or necessarily ascribed by the investigator to ZD4522) were typical of statin therapy, namely symptoms of gastrointestinal, upper respiratory disease and headache.

AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of ethical (prescription) pharmaceuticals and the supply of healthcare services. It is one of the top five pharmaceutical companies in the world with healthcare sales of over $15 billion and leading positions in sales of gastrointestinal, oncology, anaesthesia including pain management, cardiovascular, central nervous system (CNS) and respiratory products.