Rome, Italy - Data from one of the first statin trials in a South Asian population with hypercholesterolemia has shown that both atorvastatin and rosuvastatin, at doses of 10 mg and 20 mg, were well tolerated and had similar safety profiles [1]. Both drugs significantly reduced LDL-cholesterol levels, investigators report, although rosuvastatin 10 mg demonstrated statistically greater reductions in LDL and non-HDL cholesterol compared with atorvastatin 10 mg.

"South Asians have one of the highest risks for coronary heart disease and probably within the next 10 years will account for the majority of patients with heart disease in the world," said lead investigator Dr Prakash Deedwania (University of California, San Francisco). "At the present time, nearly 40 to 50 million Indians in India have coronary heart disease."

Reporting data last week at the International Symposium on Atherosclerosis, Deedwania added that recently published observational data comparing mortality among various age groups and ethnicities, involving more than 350 000 subjects in California, showed that South Asians with coronary artery disease have the highest mortality rates, even at younger ages. South Asians often have extensive disease and more disease in non-infarct-related arteries, he said, which is often coupled with an increased incidence of obesity and diabetes mellitus.

In this six-week, open-label, parallel-group study, 740 South Asian subjects—defined as those individuals from India, Pakistan, Bangladesh, Sri Lanka, Nepal, or Bhutan—with hypercholesterolemia were randomized to rosuvastatin or atorvastatin after a six-week dietary lead-in. Of these subjects, 371 were randomized to rosuvastatin, either to the 10-mg or 20-mg dose, and 369 patients were randomized to atorvastatin, also the 10-mg and 20-mg dose. In addition to elevated cholesterol levels, subjects also had two or more risk factors and a 10-year Framingham risk score >10% for CHD at randomization. Patients with CHD or CHD risk equivalent were also included in the trial.

The different drugs and doses significantly reduced LDL cholesterol as well as increased HDL-cholesterol levels. However, rosuvastatin 10 mg appeared to best atorvastatin in terms of LDL-cholesterol reduction, as well as reductions in non-HDL-cholesterol levels.

Baseline lipid values

Lipid parameter	Rosuvastatin 10 mg (n=183)	Rosuvastatin 20-mg (n=171)	Atorvastatin 10 mg (n=180)	Atorvastatin 20 mg (n=175)
LDL cholesterol (mg/dL)	156.9	153.0	158.5	155.8
HDL cholesterol (mg/dL)	43.9	44.7	43.0	43.8
Triglycerides (mg/dL)	183.7	175.2	195.9	186.6

Change from baseline

Lipid parameter	Rosuvastatin 10 mg	Atorvastatin 10 mg	p (between doses)	Rosuvastatin 20 mg	Atorvastatin 20 mg	p (between doses)
Change in LDL cholesterol (%)	-44.7	-39.6	0.0023	-49.5	-46.8	NS
Change in non-HDL cholesterol (%)	-39.8	-35.9	0.0124	-44.4	-42.1	NS
Change in HDL cholesterol (%)	6.9	6.9	NS	6.6	4.5	NS
Change in triglycerides (%)	-18.5	-19.7	NS	-21.6	-19.3	NS
Change in apolipoprotein A-1 (%)	4.1*	3.1	NS	3.3	0.3*	NS
Patients reaching NCEP ATP treatment target (%)	78.7	76.1	NS	88.9	84.6	NS

Asked by session moderator Dr Heiner Bucher (University Hospital Basel, Switzerland) about the increase in HDL cholesterol as well the increase in apolipoprotein A-1 levels observed with the drugs, Deedwania said those findings are encouraging.

"This is a short-term trial, but given the fact that South Asians have a prevalence of low HDL-cholesterol levels, particularly in the high-risk populations with existing coronary disease, perhaps an agent that would have a beneficial effect on LDL cholesterol and at the same time increase HDL cholesterol might be beneficial," said Deedwania. "Clearly, we have to do the studies to translate this into any practical terms."

Deedwania also noted that while there had been previous concerns about the pharmacokinetic profiles of the statins in an Asian population, there were similarly reported adverse events in all treatment arms. Of these, the frequency of serious adverse events was low in all treatment groups and drug discontinuations due to adverse events were also low. No cases of myopathy, rhabdomyolysis, or hepatic dysfunction were reported.