Cardiology Xagena

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Patients with heart failure: effects of LCZ696, an angiotensin II-receptor and neprilysin inhibitor, on blood pressure

The effect of LCZ696 on blood pressure was evaluated in patients with heart failure with preserved ejection fraction ( HFpEF ) in the PARAMOUNT ( Prospective comparison of ARNI with ARB on Management Of heart failUre with preserved ejectioN fracTion ) trial.

This was a phase II, randomized, parallel-group, double-blind, multicentre trial in patients with HFpEF.
Participants were randomly assigned to LCZ696 titrated to 200 mg twice daily or Valsartan titrated to 160 mg twice daily.

The PARAMOUNT trial reported blood pressure changes in both arms at 12 and 36 weeks as one of the secondary outcomes.
The trial involved 301 patients with HFpEF of which about 93% had hypertension.

After 12 weeks of treatment, blood pressure was reduced by −9.3 mmHg systolic and −4.9 mmHg diastolic in the LCZ696 group. In the Valsartan group, the systolic blood pressure was reduced by −2.9 mmHg while the diastolic blood pressure was reduced by −2.1 mmHg ( P = 0.001 for systolic and P = 0.09 for diastolic blood pressure differences ).

The significant higher reduction in blood pressure by LCZ696 when compared with Valsartan persisted at 36 weeks.

While all the previous trials provided insights into the short term antihypertensive efficacy of LCZ696, the recently published PARADIGM-HF ( Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial ) provided some data on the long-term effects of LCZ696 in patients with chronic heart failure and a reduced ejection fraction ( HFrEF ).
The trial involved 8442 HFrEF patients with 71% patients having history of hypertension.

LCZ696 ( 200 mg twice daily ) was superior to Enalapril ( 10 mg twice daily ) in reducing the risks of death and heart failure hospitalization.

In the Supplementary material published with the study results, LCZ696 showed a significant reduction in systolic blood pressure when compared with Enalapril [ mean difference −2.7 ( −3.07 to −2.34 mmHg, P less than 0.001 ) ] over a period of 3 years.

It is unclear whether the favourable effects of LCZ696 on death and heart failure hospitalization is mediated primarily by reduction in blood pressure or is independent of changes in blood pressure. ( Xagena )

Bavishi C et al, Eur Heart J 2015; First published online