“A new drug believed to cause a 20 per cent reduction in heart failure deaths could present a 'major advance' in treatment,” The Independent reports.
The drug, LCZ696, helps improve blood flow in heart failure patients. Heart failure is a syndrome caused by the heart not working properly, which can make people vulnerable to serious complications.
A new study compared LCZ696 with an existing heart failure drug called enalapril, which is also used to treat high blood pressure.
Researchers found that LCZ696 is better than enalapril for preventing death from cardiovascular causes and for preventing hospitalisation for heart failure. The results were so striking that they decided to halt the trial.
During the 27 months of the study, compared to enalapril, LCZ696:
The makers of LCZ696 must now apply for marketing authorisation before the drug can be sold. A press release from the developer of the drug, Novartis, states that it plans to file the application for marketing authorisation in the European Union in early 2015.
The study was carried out by researchers from the University of Glasgow, the University of Texas Southwestern Medical Center and Novartis Pharmaceuticals, in collaboration with an international team of researchers from other universities and research institutes around the world. It was funded by Novartis, the pharmaceutical company that developed LCZ696.
The results of the research were well covered by the UK media.
This was a randomised controlled trial. It aimed to determine whether the new drug LCZ696 reduced the risk of death from cardiovascular causes or hospitalisation for heart failure in people who had heart failure with reduced ejection fraction, compared to enalapril.
Heart failure is a syndrome caused by the heart not working properly. In heart failure with reduced ejection fraction, less blood than normal is pumped out of the heart with each beat.
Enalapril is a drug already used to treat hypertension (high blood pressure) and heart failure. Enalapril is what is known as an angiotensin-converting enzyme (ACE) inhibitor, which improves heart failure by a number of different mechanisms. It inhibits an enzyme that is part of what is known as the renin-angiotensin-aldosterone system. One of the effects of this is to cause blood vessels to relax and widen.
LCZ696 also inhibits the renin-angiotensin-aldosterone system but also inhibits another enzyme called neprilysin. It was hoped that it would be more effective in treating heart failure.
A randomised controlled trial was deemed the best way of determining whether LCZ696 reduced the risk of death from cardiovascular causes or hospitalisation for heart failure compared to enalapril.
The researchers recruited 8,442 people with heart failure and an ejection fraction of 40% or less into the trial. Ejection fraction is a measure of how well your heart beats. A normal heart pumps a little more than half the heart’s blood volume with each beat. Normal ejection fractions range between 55% and 70%. To be included in the trial, patients had to be able to tolerate both enalapril and LCZ696; this was determined in a run-in phase before people were randomised.
People were randomly assigned to receive LCZ696 (200mg twice daily) or enalapril (at a dose of 10mg twice daily), in addition to recommended therapy.
The researchers monitored how many people died from cardiovascular causes or were hospitalised for heart failure.
The researchers compared outcomes for people receiving LCZ696 with people receiving enalapril.
43 of them were later excluded due to invalid randomisation, or if their hospital site had been closed.
The trial was stopped early because outcomes with LCZ696 were much better than outcomes with enalapril.
After people had been followed for an average of 27 months:
LCZ696 also significantly reduced the symptoms and physical limitations of heart failure.
With regards to adverse effects, more people who received LCZ696 had low blood pressure (hypotension) and non-serious angioedema (swelling of the deeper layers of the skin due to a build up of fluid), but fewer people had kidney (renal) impairment, hyperkalemia (high levels of potassium in the blood) and cough than the people who received enalapril. Overall, fewer people in the LCZ696 group stopped their medication because of an adverse event than in the enalapril group.
The researchers concluded that “LCZ696 was superior to enalapril in reducing the risks of death, and of hospitalisation for heart failure.”
This was a well conducted study that achieved impressive results.
In this 27 month-long randomised controlled trial of 8,442 people with heart failure and an ejection fraction of 40% or less, compared to enalpril, the new drug LCZ696:
Marketing authorisation is now required before it can be sold. The developer of the drug, Novartis, states that they plan to file the application for marketing authorisation in the European Union in early 2015.