Healthcare Blog

FDA Approves HYZAAR(R) as First/Only Fixed-Dose Combination Hypertension Medicine to Help Prevent Stroke in Patients

August 12, 2017

Merck & Co, Inc announced that the US Food and Drug Administration (FDA) has approved another new indication for HYZAAR(R), Merck's fixed-dose combination antihypertensive drug (losartan potassium-hydrochlorothiazide tablets). HYZAAR is now 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.

The new indication for reduction in stroke is based on the landmark LIFE (Losartan Intervention for Endpoint Reduction in Hypertension) study. In March 2003, the FDA approved the same indication for Merck's antihypertensive drug COZAAR(R) (losartan potassium tablets). HYZAAR and COZAAR are the only angiotensin II receptor blockers (ARBs) to be indicated to reduce the risk of stroke in patients with hypertension and LVH. HYZAAR is the fixed dose combination of COZAAR (losartan potassium) and hydrochlorothiazide. The FDA approved this indication for HYZAAR based on:

1) the utilization of COZAAR and hydrochlorothiazide in the study - the patients in both arms were coadministered hydrochlorothiazide the majority of time they were on study drug (73.9% and 72.4% of days in the COZAAR and atenolol arms, respectively) and; 2) demonstration by Merck that the losartan and hydrochlorothiazide tablets used in the LIFE study were bioequivalent to the marketed HYZAAR tablets.

In the 9,193-patient LIFE study, treatment with a regimen based on losartan (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 losartan, and 309 in the atenolol group. Other findings from the LIFE study showed no significant difference between the treatment groups in the risk of heart attack or cardiovascular death.

"The LIFE study, for the first time, showed that a losartan-based regimen was more effective than an atenolol-based regimen at reducing the risk of stroke in patients with hypertension and LVH, despite similar blood pressure reductions in the treatment groups," said George L. Bakris, M.D., F.A.C.P., F.C.P., director, Hypertension/Clinical Research Center, Rush University Medical Center in Chicago. Blood pressure reduction measured at trough was similar for both treatment groups. At the end of the study or at the last visit before a primary endpoint, the mean blood pressures were 144.1/81.3 mmHg for the losartan-based group and 145.4/80.9 mmHg for the atenolol-based group. The difference in systolic blood pressure of 1.3 mmHg was significant (p The impact of stroke

According to the 2005 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 is the third leading cause of death and a leading cause of severe, long-term disability in the United States. Left ventricular hypertrophy, a thickening of the heart's main pumping chamber (the left ventricle), is the most common cardiac abnormality associated with longstanding hypertension and is an important predictor of the risk of stroke. Not all patients with stroke have both hypertension and LVH.

"High blood pressure is the most important risk factor for stroke," said Dr. Bakris. "Widely used guidelines state that more than two-thirds of patients with hypertension require two or more therapies to reach their blood pressure goal, one of which should usually be a thiazide-type diuretic. HYZAAR, in addition to effective blood pressure lowering, now also offers physicians an effective treatment for reducing the risk of stroke in those appropriate patients with hypertension and LVH."

New indication for HYZAAR based on LIFE trial

In the LIFE trial, 4,605 patients were randomized to receive once daily losartan 50 mg and 4,588 patients to receive once daily atenolol 50 mg. If goal blood pressure (110mmHg confirmed on two separate occasions off all antihypertensive therapy).

Selected important information about HYZAAR and COZAAR

When used in pregnancy during the second or third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, COZAAR and HYZAAR should be discontinued as soon as possible.

COZAAR and HYZAAR are contraindicated in patients who are hypersensitive to any component of these products. Because of the hydrochlorothiazide component, HYZAAR is also contraindicated in patients with anuria (absence of urine formation) or hypersensitivity to other sulfonamide-derived drugs.

HYZAAR is not recommended for patients with severe renal impairment (creatinine clearance 0.5 mg/dL) in the groups treated with HYZAAR and COZAAR, respectively, during the same time period.

About Merck

Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck discovers, develops, manufactures and markets vaccines and medicines in more than 20 therapeutic categories. The company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit merck.

Forward-Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the cautionary statements in Item 1 of Merck's Form 10-K for the year ended Dec. 31, 2004, and in its periodic reports on Form 10-Q and Form 8-K, which the company incorporates by reference.

HYZAAR(R) and COZAAR(R) are registered trademarks of E.I. du Pont de Nemours & Co., Inc., Wilmington, DE, USA.