FDA Approves COZAAR as the First and Only Hypertension Medicine to Help Prevent Stroke in Patients with Hypertension and Left Ventricular Hypertrophy

Business Wire, March 25, 2003

Business Editors/Health/Medical Writers

WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--March 25, 2003

In the landmark LIFE trial, once daily COZAAR significantly

reduced the risk of stroke

Merck & Co., Inc. today announced that the U.S. Food and Drug Administration (FDA) has approved another new indication for Merck's antihypertensive drug COZAAR(R) (losartan potassium tablets).

The new label states that COZAAR is indicated to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy (LVH), but there is evidence that this benefit does not apply to black patients. LVH, a thickening of the heart's main pumping chamber (the left ventricle), is the most common cardiac abnormality associated with longstanding hypertension. No angiotensin II receptor blocker (ARB) other than COZAAR is indicated to reduce the risk of stroke in patients with hypertension and LVH.

The new indication is based on the landmark LIFE (Losartan Intervention for Endpoint Reduction in Hypertension) study published last March in The Lancet. In this 9,193 patient study, treatment with a regimen based on COZAAR significantly reduced the risk of stroke (fatal and nonfatal) by 25 percent in patients with hypertension and LVH versus treatment with a regimen based on the beta-blocker atenolol (p=0.001). There were 232 fatal and nonfatal strokes in the group treated with COZAAR, and 309 in the atenolol group. The LIFE trial, with COZAAR, marks the first time an antihypertensive treatment regimen has demonstrated a reduction in the risk of stroke versus another antihypertensive treatment regimen in hypertensive patients with LVH. Other findings from the LIFE study showed no significant difference between the treatment groups in the risk of heart attack or cardiovascular death.

In the LIFE trial, black patients with hypertension and LVH had a lower risk of stroke on atenolol than on COZAAR. Given the difficulty in interpreting subset differences in large trials, it cannot be known whether the observed difference is the result of chance. However, the LIFE study does not provide evidence that the benefits of COZAAR on reducing the risk of cardiovascular events in hypertensive patients with left ventricular hypertrophy apply to black patients.

Stroke: A pressing national health issue

"Stroke is a leading cause of serious, long-term disability in the United States and for the victims of stroke and their families the impact can be devastating," said Richard B. Devereux, M.D., co-chairman of the LIFE study and professor of medicine at Cornell University in New York City.

According to the 2003 Update of the American Heart Association's Heart Disease and Stroke Statistics, each year an estimated 700,000 Americans experience a new or recurrent stroke. Stroke kills nearly 1 in 4 of those it strikes. Left ventricular hypertrophy is an important predictor of the risk of stroke. Hypertensive patients with LVH have approximately a two-fold increased risk of stroke as compared to hypertensive patients without LVH.

"Stroke is the third leading cause of death in the United States and hypertension is a significant and controllable risk factor for stroke," said Marvin Moser, M.D., clinical professor of medicine at Yale University and editor-in-chief of the Journal of Clinical Hypertension. "This new use for the angiotensin receptor blocker COZAAR, offers physicians an effective treatment for reducing the risk of stroke in the population of patients with hypertension and LVH."

"The new indication for COZAAR shows that it not only matters that you lower blood pressure, but it also matters how you lower blood pressure," said Dr. Devereux.

New indication based on LIFE trial that followed over 9,000 patients for an average of 4.8 years

The LIFE study was a multinational, double-blind trial designed to evaluate whether treatment with a regimen based on COZAAR would reduce the risk of the first occurrence of cardiovascular death, nonfatal stroke or nonfatal myocardial infarction (heart attack) in hypertensive patients with LVH as compared to treatment with a regimen based on atenolol. Patients were randomized to receive once daily COZAAR 50 mg or atenolol 50 mg. If goal blood pressure (Less than 140/90 mmHg) was not reached, hydrochlorothiazide (12.5 mg) was added first and, if needed, the dose of COZAAR or atenolol was then increased to 100 mg once daily. If necessary, other antihypertensive treatments (e.g., increase in dose of hydrochlorothiazide therapy to 25 mg or addition of other diuretic therapy, calcium channel blockers, alpha-blockers, or centrally acting agents, but not ACE inhibitors, angiotensin II antagonists, or beta-blockers) were added to the treatment regimen to reach the goal blood pressure.

Atenolol, a beta-blocker, is indicated in the management of hypertension; atenolol is also indicated for the long-term management of patients with angina pectoris and in the management of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality. There is evidence that atenolol is effective compared to placebo in reducing cardiovascular events, including stroke, in hypertensive patients.