SERELAXIN FOR TREATMENT OF ACUTE HEART FAILURE
WHAT IS SERELAXIN?
Serelaxin(RLX030) is a new drug targeting the relaxin receptor. Serelaxin is a recombinant form of human relaxin-2, which is known to mediate the hemodynamic changes that occur during pregnancy; it is a vasoactive peptide hormone with many biological and haemodynamic effects.
The drug is under development by Novartis for use in acute heart failure.
In a pilot study, Serelaxin was safe and well tolerated with positive clinical outcome signals in patients with acute heart failure.
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Heart failure, promising data for Serelaxin, 2013
The RELAX-AHF trial tested the hypothesis that serelaxin-treated patients would have greater dyspnoea relief compared with patients treated with standard care and placebo.
RELAX-AHF was an international, double-blind, placebo-controlled trial, enrolling patients admitted to hospital for acute heart failure; these patients were randomly assigned (1:1) with a central randomisation scheme to standard care plus 48-hours of intravenous infusion of placebo or serelaxin (30 μg/kg per day) within 16 hours from presentation. All patient had dyspnoea, increased brain natriuretic peptide (BNP), moderate renal insufficiency and systolic blood pressure greater than 125 mm Hg.
Either patients or doctors were masked to treatment assignment.
- Primary endpoint: dyspnoea improvement evaluated using two different means of measure, which are VAS AUC (visual analogue scale under the curve) and Linkert scale;
- Secondary endpoint: reduction of cardiovascular death or readmission to hospital due to heart failure or renal failure.
1161 patients were randomly assigned to serelaxin (n=581) or placebo (n=580).
Serelaxin improved the VAS AUC primary dyspnoea endpoint compared with placebo, but had no significant effect on the other primary endpoint, the Linkert scale.
No significant effects were recorded for the secondary endpoints of cardiovascular death or readmission to hospital for heart failure or renal failure.
Serelaxin treatment was associated with significant reductions of other additional endpoints, including fewer deaths at day 180 (placebo, 65 deaths; serelaxin, 42).
- Hospitalized heart failure patients showed some benefit from taking an investigational drug called serelaxin that helps relax the blood vessels.
- Patients given serelaxin experienced improved symptoms, spent less time in intensive care and had shorter hospital stays than patients given placebo, but did not have fewer hospital readmissions.
- The drug reduced cardiovascular and all-cause death.
Treatment of acute heart failure with serelaxin was associated with dyspnoea relief and improvement in other clinical outcomes, but had no effect on readmission to hospital. Serelaxin treatment was well tolerated and safe, supported by the reduced 180-day mortality.
Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF):a randomised, placebo-contolled trial, 2013
ACUTE HEART FAILURE
Heart failure is a condition in which the heart has lost the ability to pump enough blood to the body's tissues. With too little blood being delivered, the organs and other tissues do not receive enough oxygen and nutrients to function properly.
Heart failure happens when a disease affects the heart's ability to deliver enough blood to the body's tissues.
LEFT SIDED HEART FAILURE
Often, a person with heart failure may have a buildup of fluid in the tissues, called edema.
Heart failure with this kind of fluid buildup is called congestive heart failure. Where edema occurs in the body depends on the part of the heart that is affected by heart failure. Heart failure caused by abnormality of the left ventricle means that the left ventricle cannot pump blood out to the body as fast as it returns from the lungs. Because blood cannot get back to the heart, it begins to back up in the blood vessels of the lungs. Some of the fluid in the blood is forced into the breathing space of the lungs, causing pulmonary edema. A person with pulmonary edema has shortness of breath, which may be acute, severe and life threatening. A person with congestive heart failure feels tired because not enough blood circulates to supply the body's tissues with the oxygen and nutrients they need. Abnormalities of the heart structure and rhythm also can be responsible for left ventricular congestive heart failure.
RIGHT SIDED HEART FAILURE
In right-sided heart failure, the lower right chamber of the heart (right ventricle) cannot pump blood to the lungs as fast as it returns from the body through the veins. Blood then engorges the right side of the heart and the veins. Fluid backed up in the veins is forced out into the tissues, causing swelling (edema), usually in the feet and legs. Congestive heart failure of the right ventricle often is caused by abnormalities of the heart valves and lung disorders.
When the heart cannot pump enough blood, it tries to make up for this by becoming larger. By becoming enlarged (hypertrophic) the ventricle can contract more strongly and pump more blood. When this happens, the heart chamber becomes larger and the muscle in the heart wall becomes thicker.
The heart also compensates by pumping more often to improve blood output and circulation.
The kidneys try to compensate by retaining more salt and water to increase the volume of blood. This extra fluid also can cause edema. Kidneys often weaken under these circumstances, further aggravating the situation and making therapy more difficult.
The most common causes of heart failure are:
- coronary artery disease and heart attack (which may be "silent")
- high blood pressure (hypertension)
- heart valve disease
- congenital heart disease
- alcoholism and drug abuse
The most common cause of heart failure is coronary artery disease. In coronary artery disease, the arteries supplying blood to the heart become narrowed or blocked. When blood flow to an area of the heart is completely blocked, the person has a heart attack. Some heart attacks go unrecognized. The heart muscle suffers damage when its blood supply is reduced or blocked. If the damage affects the heart's ability to pump blood, heart failure develops.
Cardiomyopathy is a general term for disease of the heart muscle. It can weaken the heart, leading to heart failure.
High blood pressure is another common cause of heart failure. High blood pressure makes the heart work harder to pump blood. After a while, the heart cannot keep up and the symptoms of heart failure develop.
Defects of the heart valves, congenital heart diseases, alcoholism, and drug abuse cause damage to the heart that can all lead to heart failure.
A person with heart failure may experience the following:
- shortness of breath
- frequent coughing, especially when lying down
- swollen feet, ankles, and legs
- abdominal swelling and pain
- dizziness or fainting
- sudden death
Medical-dictionary, Heart Failure
VASODILATORS FOR TREATMENT OF AHF: RELAXIN-2
Relaxin-2 belongs to the family of Relaxins.
Novel vasodilators in heart failure, 2013
OTHER TREATMENTS OF AHF
Heart failure usually is treated with lifestyle changes and medicines. Sometimes surgery is needed to correct abnormalities of the heart or heart valves. Heart transplantation is a last resort to be considered in certain cases.
Dietary changes to maintain proper weight and reduce salt intake may be needed. Reducing salt intake helps to lessen swelling in the legs, feet, and abdomen. Appropriate exercise also may be recommended. Walking, bicycling, swimming, or low-impact aerobic exercises may be recommended. There are good heart rehabilitation programs at most larger hospitals.
Other lifestyle changes that may reduce the symptoms of heart failure include stopping smoking or other tobacco use, eliminating or reducing alcohol consumption, and not using harmful drugs.
One or more of the following types of medicines may be prescribed for heart failure:
- beta blockers
- angiotensin converting enzyme inhibitors (ACE inhibitors)
- angiotensin receptor blockers (ARBs)
- calcium channel blockers
Diuretics help eliminate excess salt and water from the kidneys by making patients urinate more often. This helps reduce the swelling caused by fluid buildup in the tissues.
Digitalis helps the heart muscle to have stronger pumping action.
Vasodilators, ACE inhibitors, ARBs, and calcium channel blockers lower blood pressure and expand the blood vessels so blood can move more easily through them. This action makes it easier for the heart to pump blood through the vessels.
Cholesterol-lowering drugs called statins can help prevent death from heart failure.
Surgery is used to correct certain heart conditions that cause heart failure. Congenital heart defects and abnormal heart valves can be repaired with surgery. Blocked coronary arteries usually can be treated with angioplasty or coronary artery bypass surgery.
With severe heart failure, the heart muscle may become so damaged that available treatments do not help. Patients with this stage of heart failure are said to have end-stage heart failure. Heart transplant usually is considered for patients with end-stage heart failure when all other treatments have stopped working.
Novel pharmacologic therapies in development for acute decompensated heart failure, 2013