Nov. 17, 2009 13:00 UTC

   

Higher Dose of Merck’s

    COZAAR^Β® (losartan potassium tablets) Significantly

    Reduced Deaths and Hospitalizations Due to Heart Failure In Investigational

    Study

Results from HEAAL Study Presented as Late-Breaker

    at American Heart Association Scientific Sessions 2009

ORLANDO, Fla.--(BUSINESS WIRE)-- In

    an investigational study, Merck & Co., Inc.'s medicine COZAAR (losartan

    potassium tablets) 150 mg, administered once daily, significantly reduced the

    risk of all-cause death or hospitalization due to heart failure compared to its

    lower 50 mg once daily dose. The Merck & Co Inc.-sponsored study compared

    the safety and efficacy of two doses of COZAAR in patients with chronic heart

    failure and reduced cardiac function (left ventricular ejection fraction) who

    were intolerant of angiotensin-converting enzyme (ACE) inhibitors. The results

    of the study, called HEAAL -- Heart failure Endpoint evaluation of the

    A-II-Antagonist Losartan -- were presented by researchers during a late breaking

    clinical trial session at the American Heart Association (AHA) Scientific

    Sessions 2009.

COZAAR is not approved for use, for any indication, at the 150 mg dose used

    in the HEAAL study. The treatment is an angiotensin II antagonist (AIIA),

    cardiovascular medicine approved in many countries in the European Union for the

    treatment of:

   
• Essential hypertension in adults and in
  
      children and adolescents 6 - 16 years of age at doses of 50 mg to 100 mg once
  
      daily.
  
     
• Renal disease in patients with hypertension and
  
      type 2 diabetes mellitus with proteinuria ≥ 0.5 g/day as part of an
  
      antihypertensive treatment.
  
     
• Chronic heart failure (in patients ≥ 60 years),
  
      when treatment with ACE inhibitors is not considered suitable due to
  
      incompatibility, especially cough, or contraindication at doses of 12.5 mg to 50
  
      mg once daily. Patients with heart failure who have been stabilised with an ACE
  
      inhibitor should not be switched to losartan. The patients should have a left
  
      ventricular ejection fraction ≤ 40% and should be clinically stable and on an
  
      established treatment regimen for chronic heart failure.
  
     
• Reduction in the risk of stroke in hypertensive
  
      patients with left ventricular hypertrophy documented by ECG at doses of 50 mg
  
      to 100 mg once daily. (The data do not support the use of losartan for this
  
      indication in black patients).

“HEAAL is the first study to examine and document the value of a higher dose

    of an angiotensin II antagonist in patients with heart failure," said lead study

    investigator Marvin A. Konstam, M.D., Chief Physician Executive, the

    Cardiovascular Center, Tufts Medical Center, and Professor of Medicine, Tufts

    University School of Medicine.

"HEAAL is another important study in a long-line of large outcomes studies

    that Merck has sponsored and conducted to help the medical community to better

    understand the role of our cardiovascular medicines in improving cardiovascular

    outcomes," said Francis Plat, M.D., Vice President and clinical therapeutic area

    head for Atherosclerosis and Cardiovascular, Merck Research Laboratories. "Like

    SOLV-D, 4S, LIFE and RENAAL, this study, too, advances our understanding of the

    role that pharmaceutical innovations can have and answers an important

    outstanding question as only a clinical outcomes trial can."

About the HEAAL Study

Study results demonstrated losartan administered in a 150 mg once daily dose,

    when compared with 50 mg per day, significantly reduced the risk of the primary

    composite endpoint (all cause death or hospitalization for heart failure) in

    patients with reduced left ventricular ejection fraction (LVEF); and reduced ACE

    inhibitor intolerance (p=0.027).

The multicenter, prospective, randomized, double-blind, event-driven clinical

    trial enrolled 3,834 patients with symptomatic congestive heart failure

    intolerant of ACE inhibitor treatment at 255 sites in 30 countries. Patients

    were randomized to two losartan treatment arms: 150 mg once daily (n=1,921) and

    50 mg once daily (n=1,913). Among these patients, 3,723 completed endpoint

    follow-up with a median follow-up time of 4.7 years. Prior to randomization,

    patients not already receiving an AIIA were titrated onto losartan from 12.5 mg

    daily to 25 mg daily over two weeks. For patients already receiving an AIIA,

    their prescription was discontinued, and investigators had the option of

    initiating open-label losartan 25 mg daily for one week or directly randomizing

    the patient.

The primary composite endpoint of the HEAAL study was all cause death or

    hospitalization for heart failure and the secondary composite endpoint was all

    cause death or cardiovascular hospitalization. Secondary symptom assessments,

    including an increase in left-ventricular ejection fraction (LVEF) function and

    changes in New York Heart Association (NYHA) classification, also were

    completed.

Patients in the 150 mg treatment group had a significantly lower risk of

    hospitalization due to heart failure or cardiovascular hospitalization compared

    to patients in the 50 mg treatment group. 450 patients in the 150 mg treatment

    group (6.0 per 100 patient-years of follow-up) were hospitalized for heart

    failure during the course of the study compared to 503 patients in the 50 mg

    treatment group (7.0 per 100 patient-years of follow-up) (p=0.025). Renal

    impairment, hyperkalameia (p<0.001), ,hypotension (p=0.002) and angioedema

    (p=0.03) as defined by the investigator were more common in the COZAAR 150 mg

    group than in the 50 mg treatment arm. Renal impairment was the adverse event

    which most commonly lead to drug discontinuation in the two groups (0.65 and

    0.49 per 100 patient years respectively) but the number (and rate) of individual

    or total discontinuations were similar for the two treatment groups.

Additional important information about COZAAR (losartan potassium

    tablets)

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, losartan should be discontinued as

    soon as possible.

Losartan is contraindicated in patients who are hypersensitive to any

    component of these products. All patients receiving thiazides should be observed

    for clinical signs of fluid or electrolyte imbalance, including hypokalemia.

   

In patients who are volume-depleted, symptomatic hypotension may occur after

    initiation of therapy. This condition should be corrected prior to

    administration of the drug, or a 25 mg dosage should be used. As with other

    drugs that block angiotensin II or its effects, concomitant use of

    potassium-sparing diuretics, potassium supplements, or salt substitutes

    containing potassium may lead to increases in serum potassium.

In clinical trials for hypertension, the most common adverse events with an

    incidence greater or equal to two percent of patients treated with losartan

    (n=1,075) and occurring more commonly than placebo (n=334) included upper

    respiratory infection (8 percent vs. 7 percent respectively), dizziness (3

    percent vs. 2 percent respectively), nasal congestion (2 percent vs. 1 percent

    respectively), and back pain (2 percent vs. 1 percent respectively).

Dosing and administration

In patients with hypertension, the usual starting dose is 50 mg once daily.

    The maximum daily dose is 100 mg. If the antihypertensive effect measured at

    trough using once-a-day dosing is inadequate, a twice-a-day regimen at the same

    total daily dose or an increase in dose may give a more satisfactory response.

   

In patients with heart failure, the usual initial dose is 12.5 mg once daily.

    The dose should generally be titrated at weekly intervals (i.e. 12.5 mg daily,

    25 mg daily, 50 mg daily) to the usual maintenance dose of 50 mg once daily, as

    tolerated by the patient.

For reduction in the risk of stroke in hypertensive patients with left

    ventricular hypertrophy documented by ECG, the usual starting dose is 50 mg once

    daily. A low dose of hydrochlorothiazide should be added and/or the dose of

    losartan should be increased to 100 mg once daily based on blood pressure

    response.

In patients who are volume-depleted, symptomatic hypotension may occur after

    initiation of the therapy. This condition should be corrected prior to

    administration of the drug, or a dosage of losartan 25 mg should be used. In

    patients with a history of hepatic impairment, a starting dose of 25 mg should

    be used. In hypertensive patients with left ventricular hypertrophy, treatment

    should be initiated with 50 mg once daily.

About Merck

Today's Merck is working to help the world be well. Through our medicines,

    vaccines, biologic therapies, and consumer and animal products, we work with

    customers and operate in more than 140 countries to deliver innovative health

    solutions. We also demonstrate our commitment to increasing access to healthcare

    through far-reaching programs that donate and deliver our products to the people

    who need them. Merck. Be Well. For more information, visit
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Forward Looking Statement

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    Reform Act of 1995. Such statements may include, but are not limited to,

    statements about the benefits of the proposed merger between Merck and

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The following factors, among others, could cause actual results to differ

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    Report on Form 10-K, Schering-Plough’s Quarterly Report on Form 10-Q for the

    quarterly period ended Sept. 30, 2009, the proxy statement filed by Merck on

    June 25, 2009 and each company’s other filings with the Securities and Exchange

    Commission (SEC) available at the SEC’s Internet site (
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COZAAR^Β® is a trademark of Merck Sharp & Dohme

    Corp., a subsidiary of Merck & Co., Inc.

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Merck & Co., Inc.
Media:
Noreen Verbrugge,

    +1-908-423-6301
or
Investor:
Carol Ferguson, +1-908-423-4465

   

Source: Merck & Co., Inc.

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