The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: A phase 2 double-blind randomised controlled trial

Scott D. Solomon, Michael Zile, Burkert Pieske, Adriaan Voors, Amil Shah, Elisabeth Kraigher-Krainer, Victor Shi, Toni Bransford, Madoka Takeuchi, Jianjian Gong, Martin Lefkowitz, Milton Packer, John J. McMurray

Research output: Contribution to journalArticle

635 Scopus citations

Abstract

Background: Heart failure with preserved ejection fraction is associated with substantial morbidity and mortality, but effective treatments are lacking. We assessed the efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor (ARNI), in patients with this disorder. Methods: PARAMOUNT was a phase 2, randomised, parallel-group, double-blind multicentre trial in patients with New York Heart Association (NYHA) class II-III heart failure, left ventricular ejection fraction 45 or higher, and NT-proBNP greater than 400 pg/mL. Participants were randomly assigned (1:1) by central interactive voice response system to LCZ696 titrated to 200 mg twice daily or valsartan titrated to 160 mg twice daily, and treated for 36 weeks. Investigators and participants were masked to treatment assignment. The primary endpoint was change in NT-proBNP, a marker of left ventricular wall stress, from baseline to 12 weeks; analysis included all patients randomly assigned to treatment groups who had a baseline and at least one postbaseline assessment. This trial is registered at Clinicaltrials.gov, number NCT00887588. Findings: 149 patients were randomly assigned to LCZ696 and 152 to valsartan; 134 in the LCZ696 group and 132 in the valsartan group were included in analysis of the primary endpoint. NT-proBNP was significantly reduced at 12 weeks in the LCZ696 group compared with the valsartan group (LCZ696: baseline, 783 pg/mL [95 CI 670-914], 12 weeks, 605 pg/mL [512-714]; valsartan: baseline, 862 pg/mL [733-1012], 12 weeks, 835 [710-981]; ratio LCZ696/valsartan, 0·77, 95 CI 0·64-0·92, p=0·005). LCZ696 was well tolerated with adverse effects similar to those of valsartan; 22 patients (15) on LCZ696 and 30 (20) on valsartan had one or more serious adverse event. Interpretation: In patients with heart failure with preserved ejection fraction, LCZ696 reduced NT-proBNP to a greater extent than did valsartan at 12 weeks and was well tolerated. Whether these effects would translate into improved outcomes needs to be tested prospectively. Funding: Novartis.

Original languageEnglish (US)
Pages (from-to)1387-1395
Number of pages9
JournalThe Lancet
Volume380
Issue number9851
DOIs
StatePublished - Oct 1 2012

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: A phase 2 double-blind randomised controlled trial'. Together they form a unique fingerprint.

  • Cite this

    Solomon, S. D., Zile, M., Pieske, B., Voors, A., Shah, A., Kraigher-Krainer, E., Shi, V., Bransford, T., Takeuchi, M., Gong, J., Lefkowitz, M., Packer, M., & McMurray, J. J. (2012). The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: A phase 2 double-blind randomised controlled trial. The Lancet, 380(9851), 1387-1395. https://doi.org/10.1016/S0140-6736(12)61227-6