LCZ696, a first-in-class compound, may improve treatment outcomes for half of all patients with heart failure, according to a Phase II clinical trial on heart failure patients with preserved ejection fraction; preserved ejection fraction is when all the heart failure signs are present, but the heart’s left ventricle pumps out more blood when it contracts compared to others with heart failure.

Dr Scott Solomon and team, of the Brigham and Women’s Hospital, USA, presented the human study results at the European Society of Cardiology 2012 Annual Congress, in Munich, Germany. Trial results have also been published today in The Lancet.

The trial’s objective was to determine whether LCZ696 might be an effective treatment option for heart failure with preserved ejection fraction. Although half of all heart failures are of this type, there is no available drug today which effectively treats the condition.

As heart failure gets worse, levels of a protein called NT-proBNP rise. Dr Scott explains that NT-proBNP levels were tested, but that patient outcomes were not. The Phase II trial tested whether participants who were administered LCZ696 experienced lower levels of NT-proBNP than those just on valsartan.

The trial demonstrated that:

  • NT-proBNO levels fell – after 12 weeks of LCZ696 treatment, NT-proBNO levels dropped significantly, compared to valsartan treatment. Valsartan is used for lowering blood pressure and is often prescribed for patients with heart failure.
  • Left atrium volume reduced – participants in the LCZ696 group also experienced physiological benefits – there was a reduction in the volume of the left atrium of the heart, which previous studies had linked to better outcomes for patients with heart failure.

Dr. Solomon said:

“LCZ696 might have beneficial effects in patients with heart failure with preserved ejection fraction and further testing of this compound could be warranted in patients with this disorder.

However, it should be noted that the results of this study are based on biomarkers and surrogate endpoints; whether the observed effects will translate into improved clinical outcomes needs prospective testing in an appropriately sized outcomes study.”

Professor John Cleland, of Castle Hill Hospital, Kingston-upon-Hull, UK, said when discussing a linked Comment in The Lancet:

“The positive results from this work will surely trigger a definitive trial. But what will the comparator be? Given that there are no known effective treatments for this type of heart failure, researchers will need to choose very carefully how they assess the efficacy of LCZ696 in treating heart failure with preserved ejection fraction.” (this quote is direct from Professor Cleveland and cannot be found in the Comment’s text)

Swiss pharmaceutical giant, Novartis, says it has not decided yet whether to advance LCZ969 into final-stage trials. Laurie Letvak, who works at the company’s critical care unit, said these results were “a critical first step”.

Novartis’ blood pressure medication, Diovan, is facing generic competition. The company, which is a major player in producing and marketing medications for cardiovascular and heart disease, needs a new replacement top-selling drug.

LCZ696 is an experimental combination medication which is being developed by Novartis. It consists of valsartan and AHU-377; both are blood pressure lowering (antihypertensive) drugs.

LCZ696 is a dual-acting angiotensin receptor-neprilysin inhibitor (ARNi).

Heart failure has nothing to do with a heart attack. Heart failure is a condition in which not enough blood is pumped around the body, because the heart is not pumping efficiently. The patient’s right, left and sometimes both sides may be affected. Heart failure signs and symptoms depend on how severe the condition is and which side is affected.

The signs and symptoms of heart failure might include:

  • Extreme fatigue (tiredness, exhaustion) – this is the most common symptom. As the body is not getting enough blood pumped through it, it focuses on the most vital organs, such as the heart and brain, and diverts blood away from the arm and leg muscles and other less vital parts of the body.
  • When the left side of the body is affected:

    – Dyspnea (breathlessness) – more noticeable when the patient is either lying down or active.
    – Coughing with frothy spit

  • When the right side of the body is affected:

    – The ankles and/or legs swell
    – Enlarged stomach
    – Enlarged liver

  • When both side of the body are affected

    – Confusion
    – Dizziness
    Constipation
    – Nausea
    – Reduced appetite

Written by Christian Nordqvist