LCZ696 could be of PARAMOUNT importance in heart failure

Aug 31 2012

By medwireNews Reporters

The first-in-class angiotensin receptor neprilysin inhibitor LCZ696 could improve treatment of heart failure (HF), report researchers who conducted a phase II trial of the drug and found it had superior results to an alternative therapy already in use.

Primary results from 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 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 a significant 4.40 mL decrease in left atrial volume in the LCZ696 group after 36 weeks of treatment, compared with an increase of 0.25 mL in the valsartan group.

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

NT-proBNP levels 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.

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."

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