Greater reduction of LV mass index with ARNI than with ARB in hypertensive patientsLiterature - Schmieder RE, Wagner F, Mayr M, et al. - Eur Heart J 2017; published online ahead of print
CV remodeling has been associated with increased CV risk, as demonstrated in community-based cohorts and patients with essential hypertension [1,2], and is therefore an important treatment target. The dual-action sacubitril/valsartan, a relatively new drug, inhibits neprilysin and disrupts angiotensin II signaling through blockade of the angiotensin receptor (ARB) [3,4]. This drug has been demonstrated to reduce the risk of the composite end point of CV death, heart failure hospitalization, CV death and death from any cause in patients with heart failure compared to the ACE-inhibitor enalapril .
The effects of sacubitril/valsartan on LV mass and large arteries compared to the ARB olmesartan were studied in a multi-center, randomized, double-blind, double-dummy, active-controlled, parallel group trial in patients with hypertension and elevated pulse pressure (PP). 114 patients were randomized in a 1:1 ratio to receive sacubitril/valsartan (n=57) or olmesartan (n=57) for 52 weeks.
- SBP was decreased in the sacubitril/valsartan group compared to the olmesartan group after 52 weeks of treatment (26.1 mmHg vs 20.8 mmHg, respectively, 95%CI:-9.46 to -0.53, P=0.028], whereas no difference in SBP was observed between the two groups after 12 weeks, nor for levels of DBP after both 12 and 52 weeks.
- No treatment differences were observed for changes from baseline to 12 and 52 weeks in local distensibility of ascending aorta, proximal descending aorta, or distal descending aorta.
- LV mass was decreased in both groups, but a greater reduction was observed in the sacubitril/valsartan group than in the olmesartan group with a treatment difference of 8.0966 g (95% CI:-15.9848 to -0.2084, P=0.049) after 12 weeks and -5.1942 g (95%CI: -10.65 to 0.26, P=0.062) after 52 weeks.
- A greater reduction was observed when LV mass was adjusted for body surface area (LV mass index) in the sacubitril/valsartan group than in the olmesartan group; the treatment difference was -4.05 g/m2 (95% CI: -7.90 to -0.20, P=0.039] from baseline to 12 weeks and -3.27 g/m2 (95% CI: -6.21 to -0.34), P= 0.029) to 52 weeks.
- Adjusting for the changes in SBP at 12 and 52 weeks resulted in treatment differences of LV mass index of -3.57 g/m2 (95% CI: -7.32 to 0.18, P=0.0619) and -2.80 g/m2 (95% CI: -5.63 to 0.04, P=0.0529), respectively, with a greater, but non-significant reduction in the sacubitril/valsartan group than the olmesartan group.
- Central PP was significantly more decreased in the sacubitril/valsartan group compared to the olmesartan group after 52 weeks with a mean difference of -3.50 mmHg (95% CI: -6.15 to -0.85, P=0.010).
In patients with hypertension, treatment with sacubitril/valsartan was associated with superior reductions of LV mass after 12 and 52 weeks and central PP after 52 weeks compared to treatment with olmesartan, suggesting that sacubitril/valsartan may lead to a better cardiovascular prognosis in this patient population than olmesartan.