Beneficial effects of antihypertensive therapy on central hemodynamics
Effects of Sacubitril/Valsartan Versus Olmesartan on Central Hemodynamics in the Elderly With Systolic Hypertension. The PARAMETER Study
Background
Systolic hypertension and increased pulse pressure (PP) are indicative of arterial ageing and stiffening, and predict incident cardiovascular disease, stroke, chronic kidney disease, and heart failure [1,2]. Moreover, arterial stiffening causes elevations of the central aortic systolic pressure (CASP) and PP relative to brachial pressures, leading to reduced aortic:brachial pressure pulse amplification [3]. While antihypertensive therapies in elderly patients reduce systolic blood pressure (SBP), cardiovascular morbidity and mortality, they have differential effects on central aortic pressures, despite the similar effects on brachial blood pressure [4,5].
In this study, the short- and long-term effects at 12 and 52 weeks of sacubitril/valsartan in comparison with olmesartan were assessed on CASP and other measures of central hemodynamics and arterial stiffness. This was measured in 367 elderly patients with elevated SBP and increased PP.
Main results
- The mean reductions in CASP after 12 weeks were −12.6 mmHg (95% CI: −14 to −10.1) with sacubitril/valsartan and −8.9 mmHg (95% CI: −11.1 to −6.7) with olmesartan.
- The least squares mean (LSM) reductions in CASP were superior with sacubitril/valsartan versus olmesartan with a between-treatment difference of −3.7 mmHg (95% CI: −6.4 to −0.9 mmHg; P=0.01).
- At 12 weeks, the LSM reductions in central aortic PP (CAPP) were superior with sacubitril/valsartan versus olmesartan with a between-treatment difference of −2.4 mmHg (P=0.01).
- Sacubitril/valsartan lowered mean sitting SBP and mean sitting PP to a greater extent than olmesartan at week 12 (between-treatment difference -3.8 and -2.8, respectively), but not central aortic diastolic pressure or mean sitting DBP.
- The LSM reductions in mean 24-hour ambulatory brachial and central aortic systolic pressures were significantly greater with sacubitril/valsartan versus olmesartan after 12 weeks, with a between-treatment difference of −4.1 mm Hg (P<0.001) for mean ambulatory SBP and −3.4 mmHg (P<0.001) for mean ambulatory CASP.
- Night-time reductions in mean ambulatory CASP (−5.2 mmHg) and mean ambulatory SBP (−5.9 mmHg) were significantly (P<0.001) greater with sacubitril/valsartan compared with olmesartan with the greatest differences in the early morning hours in mean ambulatory CASP (−6.3 mmHg) and mean ambulatory SBP (−6.9 mmHg).
- The requirement of an add-on antihypertensive therapy was significantly lower in patients treated with sacubitril/valsartan versus olmesartan (P<0.002) from weeks 12 to 52.
- The reduction in the geometric mean plasma NT-proBNP from baseline to week 12 was greater in patients treated with sacubitril/valsartan (34%) compared with olmesartan (20%), and this difference was attenuated by week 52.
- Treatments with both sacubitril/valsartan and olmesartan were generally well tolerated and adverse events were balanced between treatment groups.
Conclusion
In elderly patients with elevated SBP and PP, sacubitril/valsartan was superior compared with olmesartan in reducing sitting and ambulatory central aortic and brachial pressures. The greater reduction in NT-proBNP and PP observed with sacubitril/valsartan indicates a de-stiffening effect of sacubitril/valsartan and a reduction in cardiac wall stress. These findings suggest that sacubitril/valsartan provides beneficial effects on central aortic hemodynamics.
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