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27-08-2012 | Cardiology | Article

LCZ696 findings of PARAMOUNT importance

medwireNews: A phase II trial of the first-in-class angiotensin receptor neprilysin inhibitor, LCZ696, has shown that the compound may improve treatment of heart failure (HF) patients.

The primary results of the PARAMOUNT study, which involved 301 patients with New York Heart Association (NYHA) class II-III HF, revealed that LCZ696 200 mg twice daily reduced levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), a marker of left ventricular wall stress, to a greater extent at 12 weeks than did valsartan 160 mg twice daily.

Among patients who completed the study, NT-proBNP declined from 783 pg/mL at baseline to 605 pg/mL at 12 weeks in the 134 patients treated with LCZ696, compared with a decline from 862 pg/mL at baseline to 835 pg/mL at 12 weeks in the 132 patients treated with valsartan. This corresponded to a ratio of change with LCZ696/valsartan of 0.77.

However, lead author Scott Solomon (Brigham and Women's Hospital, Boston, Massachusetts, USA), who presented the findings at this year's European Society of Cardiology Annual Congress, warned that the results are hypothesis-generating and do not have clinical implications at this stage.

Speaking to medwireNews, he explained: "This is a phase II proof-of-concept trial that should allow us to have enough confidence to go ahead with an outcomes trial. We need to do an outcomes trial to demonstrate improvements in morbidity and mortality to use this therapy.

"These are very promising results that should point us in the direction of doing a definitive pivotal trial."

Secondary findings included that left atrial volume was significantly reduced by 4.40 ml in the LCZ696 group after 36 weeks of treatment, compared with an increase of 0.25 ml in the valsartan group.

Meanwhile, change in NYHA class did not differ significantly between the groups at 12 weeks. However, at 36 weeks NYHA class had improved in 25% of patients treated with LCZ696, compared with 15% of those treated with valsartan.

The level of NT-proBNP remained reduced at 36 weeks in the LCZ696 group, at 480 pg/mL, but the difference between the treatment groups at this time point was no longer significant.

"The primary endpoint of this trial was actually the earlier endpoint of 12 weeks," commented Solomon in a press briefing ahead of his presentation. "Over time, we saw that the reduction in the NT protein with LCZ696 was sustained. We saw a gradual decline in the NT protein in patients with valsartan so it may be that the mechanism of the onset of action or the speed of action was simply faster in LCZ696.

"However, this appeared to translate into improvement in the other domains: left atrial size and NYHA. So maybe this early reduction has important physiological significance."

Speaking to medwireNews, Richard Pacher, (Medical University of Vienna, Austria), an expert on HF, said: "PARAMOUNT is the first study indicating that this new compound, consisting of an angiotensin-receptor blocker and reinforcing the vasodilating power of natriuretic peptides, shows earlier decrease of NT-proBNP."

The full results of PARAMOUNT were also released online in The Lancet to coincide with their presentation at the Congress.

Conference website http

Lancet 2012; Advance online publication

medwireNews (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012

By Piriya Mahendra, medwireNews Reporter

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