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The recently designated ARNI - angiotensin receptor/neprilysin inhibitor - of sacubitril/valsartan (also known as LCZ696) has already proved its efficacy in heart failure in the PARADIGM trial, reported at last year’s ESC Congress. Now, in a bid to extend its indication, the PARAMETER study has shown that this same combination of sacubitril/valsartan significantly reduced central aortic systolic pressure (CASP) and central aortic pulse pressure (CPP) when compared to the standard ARB olmesartan in elderly patients with hypertension.
‘An important finding of this trial,’ said presenter Bryan Williams from University College, London, ‘is that LCZ696 had an especially powerful effect on reducing night-time blood pressure – a strong predictor of cardiovascular risk.’
Following a wash-out period, 454 elderly hypertensive patients (mean age 68 years) were randomised to sacubitril/valsartan 400 mg qd or olmesartan 40 mg qd at 48 study sites in 12 countries.
Results at 12 weeks showed that LCZ696 reduced systolic blood pressure by 12.6 mmHg compared to 8.9 mmHg for olmesartan (P=0.01). Data further showed that LCZ696 reduced CPP by 6.4 mmHg, while olmesartan reduced it by 4.0 mmHg (P=0.012). The 24-hour ambulatory blood pressure was reduced by an additional 4.1 mmHg for LCZ696 patients, and central systolic blood pressure by an additional 3.3 mmHg (P<0.001 for both).
At 52 weeks no difference was found between the two regimens for central and brachial blood pressure, due to the allowance of add-on therapy. However, while 47% of patients taking olmesartan required add-on medication to achieve blood pressure control, only 32 % receiving LCZ696 did so.
Finally LCZ 696 produced a 34% reduction in background NT-pro BNP (the precursor for BNP in the circulation) compared to 20% for olmesartan. Safety data demonstrated no significant differences in adverse events between the two groups.
The holy grail of systolic hypertension therapy, said Williams, is to achieve a ‘destiffening’ effect. The fact that release of BNP was reduced for LCZ696 provides indirect evidence that this may be occurring. ‘Currently studies are under way using MRI to directly measure changes in arterial distensibility following LCZ696 treatment,’ said Williams.
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