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Hypertension: Valsartan / Sacubitril reduces aortic systolic blood pressure and pulse pressure compared to the standard angiotensin receptor blocker

The combination drug Valsartan / Sacubitril known as LCZ696 ( Entresto ) significantly reduced aortic systolic blood pressure and pulse pressure compared to the standard angiotensin receptor blocker ( ARB; sartan ) Olmesartan ( Benicar ) in patients with hypertension, according to results of the PARAMETER study.

The findings have shown novel and beneficial effects of the combination drug Valsartan / Sacubitril, an angiotensin receptor / neprilysin inhibitor ( ARNI ), that may afford greater protection against heart disease, stroke and heart failure than currently available treatment strategies.

An important and unprecedented finding of this trial is that Valsartan / Sacubitril also had an especially powerful effect on reducing night-time blood pressure, which is a strong predictor of cardiovascular risk.

The PARAMETER study included 454 older patients ( mean age 68 years ) at high risk of heart failure because of systolic hypertension ( HTN ) and a wide pulse pressure ( PP ), which is the difference between the systolic and diastolic pressure readings.
Wide PP is associated with age-related stiffening of the arteries.

As arteries stiffen, the pressure in the aorta rises faster than the pressure measured in the arm.

Patients were randomised to once daily Valsartan / Sacubitril ( 200 mg ) or Olmesartan ( 20 mg ) for 4 weeks, followed by a forced-titration to double the initial doses for the next 8 weeks.

The primary outcome of the study was reduction from baseline to week 12 in central aortic systolic pressure ( CASP ), with secondary outcomes including reduction from baseline to week 12 in central aortic pulse pressure ( CPP ) and 24-hour ambulatory brachial and central systolic blood pressure ( SBP ).

After 12 weeks, patients treated with Valsartan / Sacubitril had a 3.77 mmHg greater reduction in CASP and a 2.4 mmHg greater reduction in CPP from baseline compared to patients treated with Olmersartan ( P=0.01 and P=0.012 respectively ).

The 24-hour ambulatory brachial and central SBPs were significantly reduced from baseline to 12 weeks in both treatment arms, with Valsartan / Sacubitril lowering brachial SBP by an additional 4.1 mmHg and central SBP by an additional 3.3 mmHg compared to Olmesartan ( P less than 0.001 for both ).
This finding was most pronounced during the night-time period.

Add-on hypertension medication was allowed at 12–24 weeks if adequate blood pressure control had not been attained, and a higher percentage of patients treated with Olmesartan required add-on medication to improve their blood pressure when compared to patients in the Valsartan / Sacubitril group ( 47% versus 32% ).

Finally, in an exploratory analysis of the carotid-to-femoral pulse wave velocity, a measure of arterial stiffness, the researchers noted a trend toward greater improvement in a subgroup of Valsartan / Sacubitril-treated patients with the stiffest arteries at baseline.

This is consistent with the hypothesis that the better reduction in aortic pressure with Valsartan / Sacubitril was related to an improvement in the function of stiffened arteries in older people.

PARAMETER is the first randomized study demonstrating the ability of Valsartan / Sacubitril to significantly reduce central blood pressure and pulse pressure, compared to a sartan, in high-risk older patients with systolic hypertension and a wide pulse pressure.
These data are important because lowering systolic and pulse pressure in older people with stiffened arteries is an unmet need in endeavour to reduce the risk of cardiovascular disease and heart failure in older people. ( Xagena )

Source: European Society of Cardiology ( ESC ) Meeting, 2015