LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, may be more effective in lowering central aortic systolic pressure and central aortic pulse pressure than the angiotensin receptor blocker (ARB) olmesartan in elderly patients with hypertension, according to results from the PARAMETER study presented Aug. 31 during ESC Congress 2015 in London.

The 52-week multi-center study randomized 454 patients with hypertension aged ≥60 years with a mean sitting systolic blood pressure (SBP) of ≥150 to <180 and a pulse pressure of >60 mm Hg to once daily LCZ696 (200 mg) or olmesartan (20 mg) for four weeks, followed by a forced-titration to double the initial doses for the next eight weeks. At 12–24 weeks, if the BP target had not been attained, amlodipine (2.5–5 mg) and subsequently hydrochlorothiazide (6.25–25 mg) were added. The primary and secondary endpoints were changes from baseline in central aortic systolic pressure and central aortic pulse pressure at week 12, respectively.

Results showed that after 12 weeks, patients treated with LCZ696 had a 3.77 mmHg greater reduction in central aortic systolic pressure and a 2.4 mmHg greater reduction in central aortic pulse pressure from baseline compared to patients treated with olmesartan. Additionally, 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. This finding was most pronounced during the nighttime.

In other findings, a greater percentage of patients treated with olmesartan (47 percent) required additional hypertension medication at weeks 12–24 compared to patients in the LCZ696 group (32 percent). Investigators also noted that an exploratory analysis of the carotid-to-femoral pulse wave velocity – indicated a trend toward greater improvement in a subgroup of LCZ696-treated patients with the stiffest arteries at baseline.

"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 hypertension and a wide pulse pressure," said lead investigator Bryan Williams, MD, from University College London. "These data are important because lowering systolic and pulse pressure in older people with stiffened arteries is an unmet need in our endeavor 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."

Keywords: ESC Congress, Amlodipine, Aged, Aminobutyrates, Angiotensin Receptor Antagonists, Arteries, Blood Pressure, Heart Failure, Hypertension, Hydrochlorothiazide, Hypertension, Imidazoles, Neprilysin, Pulse Wave Analysis, Receptors, Angiotensin, Tetrazoles

< Back to Listings