New heart drug beats current gold standard

Clinical trials of a new drug to treat heart failure were brought to an early close after results showed it outperformed the current gold standard. Writing in the New England Journal of Medicine, researchers from the University of Glasgow said: “The trial was stopped early, according to prespecified rules, after a median follow-up of 27 months, because the boundary for an overwhelming benefit with LCZ696 had been crossed.” In a double blind-trial, 8,442 patients with heart failure were given either 200mg of LCZ696 (a angiotensin receptor-neprilysin inhibitor), or 10mg of enalapril – the current recommended treatment – twice daily, in addition to recommended therapy. Researchers compared mortality rates and hospitalisation for heart failure with early results showing 21.8% of patients in the LCZ696 group died of cardiovascular causes versus 26.5% in the enalapril group. A further 17% of patients on the new drug died of other causes, compared with 19.8% in the other group. This 20% reduction in death from cardiovascular causes – and 16% reduction in other causes – is “highly statistically significant and clinically important”. The new drug also reduced hospitalisation for heart failure by 21% and improved the symptoms and physical limitations more than enalapril. But patients given LCZ696 in the Novartis-funded trial did have slightly more hypotension and non-serious angioedema, but less renal impairment, hyperkalemia and cough than the other group. When the heart is damaged, the body lowers the flow of blood by stimulating the production of angiotensin II and noradrenaline, which constrict blood vessels and make it harder for the failing heart to squeeze blood into them. “Enalapril works by blocking or inhibiting these hormones and by doing so slows down or even reverses the progressive worsening of the condition,” said Professor John McMurray who co-led the trial. “What this new drug LCZ696 does is simultaneously inhibit the bad hormones – like enalapril – but in addition boost the production of beneficial hormones.” Several of these beneficial substances stimulate the kidneys to produce more urine, to excrete sodium and water, and act to relax blood vessels. All of these actions unload the failing heart,” he continued. “By having this dual effect LCZ696 had extra beneficial actions compared with enalapril and in this way improved patient outcomes.” Angiotensin-neprilysin inhibition versus enalapril in heart failure