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The combination drug valsartan/sacubitril known as LCZ696 significantly reduced aortic systolic blood pressure and pulse pressure compared to the standard angiotensin receptor blocker (ARB) olmesartan in patients with hypertension, according to results of the PARAMETER study.
EMBARGO 31 August 2015 at 09:00 BST
STUDY NAME: The PARAMETER Trial
SESSION NAME: Hot Line IV - Hypertension
The findings, presented today at ESC Congress 2015, show “novel and beneficial effects” of LCZ696 – an angiotensin receptor/neprilysin inhibitor (ARNI) - “that may afford greater protection against heart disease, stroke and heart failure than currently available treatment strategies,” said Bryan Williams, MD, the study’s principal investigator, and Chair of Medicine at University College London, UK.
“An important and unprecedented finding of this trial is that LCZ696 also had an especially powerful effect on reducing night-time blood pressure – which is a strong predictor of cardiovascular risk,” he added.
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, explained Professor Williams.
“As arteries stiffen, the pressure in the aorta (close to the heart) rises faster than the pressure measured in the arm, and that is the reason we were interested to see if LCZ696 was more effective at reducing this pressure compared to an ARB alone.”
Patients were randomised to once daily LCZ696 (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 LCZ696 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 LCZ696 lowering brachial SBP by an additional 4.1 mmHg and central SBP by an additional 3.3 mmHg compared to olmesartan (P<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 LCZ696 group (47% versus 32%), reported Professor Williams.
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 LCZ696-treated patients with the stiffest arteries at baseline.
“This is consistent with our hypothesis that the better reduction in aortic pressure with LCZ696 was related to an improvement in the function of stiffened arteries in older people,” he commented.
“PARAMETER is the first randomized study demonstrating the ability of LCZ696 to significantly reduce central blood pressure and pulse pressure, compared to an ARB, in high-risk older patients with systolic HTN and a wide PP,” concluded Professor Williams.
“These data are important because lowering systolic and pulse pressure in older people with stiffened arteries is an unmet need in our endeavour to reduce the risk of cardiovascular disease and heart failure in older people. Our results suggest that LCZ696 has been able to achieve more in this regard than existing treatments, it is an exciting advance.”
SOURCES OF FUNDING: The study was an investigator-led study funded by Novartis Pharma AG, Basel, Switzerland.
DISCLOSURES: Professor Williams has received honoraria for lectures on hypertension from Novartis Pharma.
ESC Press OfficeFor background information, please contact the ESC Press Office.For independent comment on site, please contact the ESC Spokesperson coordinator: +44 7785 467 947
About the European Society of CardiologyThe European Society of Cardiology (ESC) represents more than 90 000 cardiology professionals across Europe and worldwide. Its mission is to reduce the burden of cardiovascular disease in Europe. About ESC Congress 2015ESC Congress is the world’s largest and most influential cardiovascular event contributing to global awareness of the latest clinical trials and breakthrough discoveries. ESC Congress 2015 takes place 29 August to 2 September at ExCel London in London, UK. Access the scientific programme. More information is available from the ESC Press Office at firstname.lastname@example.org.To access all the scientific resources from the sessions during the congress, visit ESC Congress 365. This press release accompanies both a presentation and an ESC press conference at the ESC Congress 2015. Edited by the ESC from material supplied by the investigators themselves, this press release does not necessarily reflect the opinion of the European Society of Cardiology. The content of the press release has been approved by the presenter.
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