ASCOT Trial - Amlodipine Reduces Cardiovascular Mortality
By Pfizer
Sep 8, 2005, 01:05

Results of the landmark Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) showed that patients with high blood pressure and additional cardiovascular risk factors who received a treatment regimen based on Pfizer's calcium channel blocker Norvasc (amlodipine besylate) experienced significant reductions in cardiovascular death, all-cause mortality and total cardiovascular events and procedures, including heart attacks and strokes, compared to patients who received a standard beta-blocker based regimen.

Patients receiving the Norvasc-based regimen experienced a reduction in the primary endpoint (fatal coronary heart disease and non-fatal heart attack) which did not reach statistical significance. The final results of ASCOT confirmed the Data Safety and Monitoring Board decision to stop the trial early.

The results were presented this week at the annual meeting of the European Society of Cardiology in Stockholm, and September 4 online issue of The Lancet.

"The results of ASCOT clearly demonstrate that a Norvasc-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 who had high blood pressure. The trial compared the cardiovascular effects of a Norvasc-based regimen versus a standard beta-blocker based regimen in reducing cardiac events in patients with hypertension and multiple cardiovascular risk factors. In the Norvasc-based regimen, patients received the ACE-inhibitor perindopril and the alpha-blocker 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 a diuretic (thiazide) and Cardura XL (doxazosin GITS), if needed.

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

"We have shown that an effective treatment strategy can provide the optimal benefits for patients and even save lives if physicians focus on early intervention that begins with targeting hypertension along with other cardiovascular risk factors such as lowering cholesterol with Lipitor," said Professor Sever.

In addition to treatment for high blood pressure, 10,000 patients in ASCOT who had normal to mildly elevated cholesterol levels—not typical candidates for lipid-lowering treatment—received Lipitor 10mg (atorvastatin calcium) 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 benefit in the reduction of heart attacks in Lipitor-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 high blood pressure.

"The ASCOT results, including results of the Lipitor arm, play an essential role in effectively reducing cardiovascular events and death in hypertensive patients with additional risk factors," said Dr. Michael Berelowitz, Pfizer's senior vice president of Worldwide Medical and Outcomes Research. "These results imply that physicians may want to consider a more comprehensive approach to managing overall cardiovascular risk which may involve other available therapies such as Caduet, which offers the benefits of Norvasc and Lipitor in a single tablet."

Hypertension is one of the most prevalent risk factors for cardiovascular disease, affecting as many as 800 million people worldwide. It is estimated that at least 80 percent of people with high blood pressure may also have other uncontrolled cardiovascular risk factors with elevated cholesterol being the most common.

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 Norvasc-based regimen.

Caduet is a prescription drug that combines 2 medicines, Norvasc® (amlodipine besylate) and Lipitor® (atorvastatin calcium). It is used to treat both high blood pressure (hypertension) or angina (chest pain) and high cholesterol, or to lower the risk of heart attack in patients with multiple risk factors for heart disease—such as family history of heart disease, high blood pressure, older than 55, low HDL-C, or smoking—along with diet and exercise.

Caduet is not for everyone. It is not for those with liver problems. And it is not for women who are nursing, are pregnant, or may get pregnant. Patients should tell their doctor if they feel any new muscle pain or weakness. This could be a sign of serious side effects. Patients should also tell their doctor about other medicines they are taking. This may help avoid serious drug interactions. The doctor may do blood tests to check liver function before and during treatment. If a patient has any heart problems, they should tell their doctor before taking Caduet. The most common side effects are edema, headache, and dizziness. They tend to be mild and often go away.

Norvasc (amlodipine besylate) is indicated for high blood pressure and angina. In clinical trials, the most common side effects for Norvasc versus placebo were edema (8.3% vs 2.4%), headache (7.3% vs 7.8%), fatigue (4.5% vs 2.8%), and dizziness (3.2% vs 3.4%).

The most common side effects are swelling, headache and dizziness. They tend to be mild and often go away. Patients should talk to their doctor about all medicines they are taking to help avoid serious drug interactions. Doctors may do blood tests to check liver function before and during treatment. Patients treated with Caduet should tell their doctor if they feel any new muscle pain or weakness which could be a sign of serious side effects.

All rights reserved by