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Independence of the blood pressure lowering effect and efficacy of LCZ696, an angiotensin receptor neprilysin inhibitor, in patients with heart failure with preserved ejection fraction


The first in class angiotensin receptor neprilysin inhibitor, LCZ696 has been shown to reduce levels of N-terminal pro-brain natriuretic peptide ( NT-proBNP ), reduce left atrial size and improve New York Heart Association ( NYHA ) class in patients with heart failure with preserved ejection fraction ( HFpEF ).

Researchers have examined whether the effects of LCZ696 were independent of systolic blood pressure ( SBP ) lowering.

In the PARAMOUNT ( Prospective comparison of ARNi ( angiotensin receptor neprilysin inhibitor ) with ARB ( angiotensin receptor blocker ) on Management Of heart failUre with preserved ejectioN fracTion ) trial 301 patients were randomly assigned to LCZ696 or Valsartan.

The relationship between systolic blood pressure lowering and LCZ696 on NT-proBNP level, left atrial size, NYHA class and estimated glomerular filtration rate (eGFR), was examined.

By 12 weeks blood pressure was reduced by 9 mmHg / 5 mmHg in patients receiving LCZ696 in comparison with 3 mmHg / 2 mmHg in those receiving Valsartan.

The change in NT-proBNP was poorly correlated with change in systolic blood pressure ( LCZ696, r = 0.17, P = 0.06; Valsartan, r = 0.05, P = 0.58 ).
After adjustment for change in systolic blood pressure, the ratio of change in NT-proBNP at 12 weeks for LCZ696 vs. Valsartan was 0.76 ( 95% CI 0.63-0.93, P = 0.008 ), and similar to the ratio not adjusting for systolic blood pressure ( 0.76, 95% CI 0.63-0.92, P = 0.006 ); P for interaction was 0.38 ).

Similarly, reduction in left atrial volume index at 36 weeks, improvement in NYHA class and eGFR were all independent of the change in systolic blood pressure.

In conclusion, in patients with HFpEF, the effect of the angiotensin receptor neprilysin inhibitor LCZ696 on NT-proBNP, left atrial volume, functional class, and eGFR was independent of reduction in systolic blood pressure. ( Xagena )

Jhund PS et al, Eur J Heart Fail 2014;16:671-677

XagenaMedicine_2014



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