Patients with hypertension and other cardiovascular risk factors treated with an amlodipine besylate-based regimen have significant reductions in cardiovascular mortality, all-cause mortality, and total cardiovascular events and procedures compared with patients treated with a standard beta-blocker-based regimen, according to a study presented at the annual meeting of the European Society of Cardiology and published simultaneously online by Lancet.

Results of the landmark Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) showed that patients who received treatment based on amlodipine besylate did not have a statistically significant reduction in the primary endpoint of fatal coronary heart disease and nonfatal myocardial infarction, but the overall final results of the trial confirmed the decision by the Data Safety and Monitoring Board to stop the trial early.

"The results of ASCOT clearly demonstrate that a Norvasc (amlodipine)-based antihypertensive regimen can reduce the risk of cardiovascular death and a broad range of cardiovascular events in patients with hypertension who have additional risk factors," said Professor Peter Sever, ASCOT principle investigator, clinical pharmacology and therapeutics, International Centre for Circulatory Health at London's Imperial College.

The five-year ASCOT Study, which was one of the largest hypertension trials ever conducted, involved over 19,000 patients in Europe. In the amlodipine-based regimen, patients received perindopril and Cardura XL (doxazosin GITS) as add-on therapy if additional blood pressure control was needed. Patients receiving the beta-blocker-based regimen of atenolol received thiazide and Cardura XL if needed as add-on therapy.

The final ASCOT results showed an 11-percent reduction in total mortality in patients taking the amlodipine-based regimen compared with patients taking the beta-blocker-based regimen. Amlodipine patients also experienced a 23-percent reduction in fatal and non-fatal strokes and a 24-percent reduction in cardiovascular mortality compared with patients taking the beta-blocker-based regimen. In addition, amlodipine patients had a 10-percent reduction in the primary endpoint of fatal coronary heart disease and non-fatal heart attack, a difference that did not reach statistical significance.

In addition to treatment for hypertension, 10,000 patients in ASCOT who had normal to mildly elevated cholesterol levels-- not typical candidates for lipid-lowering treatment--received atorvastatin 10mg or placebo to evaluate the cardiovascular benefits of lipid-lowering therapy. In October 2002, the lipid-lowering arm of ASCOT was stopped earlier than expected due to a significant reduction in myocardial infarctions in statin-treated patients.

The results of the lipid lowering arm of ASCOT provided critical information in the development of national guidelines including the National Cholesterol Education Program and the Joint European Guidelines, which now call for more aggressive lipid lowering in patients who have elevated cardiovascular risk, including patients with hypertension.

Funded by Pfizer, ASCOT was an investigator-led trial coordinated by an independent steering committee. The study began in 1998 and enrolled patients in the United Kingdom, Ireland, Sweden, Norway, Denmark, Finland and Iceland. In December 2004, the ASCOT steering committee endorsed the recommendation of the Data and Safety Monitoring Board to stop the trial early due to favorable benefits, including mortality, demonstrated in patients who received the amlodipine-based regimen.