Correlations of plasma renin activity and aldosterone concentration with ambulatory blood pressure responses to nebivolol and valsartan, alone and in combination, in hypertension

Abstract

After demonstration of the antihypertensive efficacy of the combination of the beta-blocker nebivolol and the angiotensin receptor blocker valsartan in an 8-week, randomized, placebo-controlled trial (N = 4161), we now report the effects of this treatment on the renin-angiotensin-aldosterone system in a substudy (n = 805). Plasma renin activity increased with valsartan (54%-73%) and decreased with nebivolol (51%-65%) and the combination treatment (17%-39%). Plasma aldosterone decreased with individual treatments (valsartan, 11%-22%; nebivolol, 20%-26%), with the largest reduction (35%) observed with maximum combination dose (20 mg nebivolol/320 mg valsartan). Baseline ln(plasma renin activity) correlated with the 8-week reductions in 24-hour systolic and diastolic BP following treatments with the combination (all doses combined, P = .003 and P < .001) and nebivolol (both, P < .001), but not with valsartan. Baseline ln(aldosterone) correlated with 24-hour systolic and diastolic BP reductions following combination treatment only (P < .001 and P = .005). The implications of the renin-angiotensin-aldosterone system effects of this beta blocker-angiotensin receptor blocker combination should be explored further.

Plasma renin activity in patients with heart failure and reduced ejection fraction on optimal medical therapy

“…Indeed, ACE-i and ARB tend to lower aldosterone concentrations, but increase PRA, while beta-blockers might lower both, and MRA increase both. 31 – 37 Although none of the patients included in this study were taking an angiotensin receptor blocker-neprilysin inhibitor (ARNI), in light of the new HF guidelines it may be interesting to point out that previous studies have demonstrated that the association of sacubitril, a neprilysin inhibitor, does not affect PRA or serum aldosterone concentration. 38 , 39 Hypertensive patients treated with neurohormonal blockers demonstrate increased PRA and plasma aldosterone levels.…”

Rationale for nebivolol/valsartan combination for hypertension

“…A substudy conducted within the NAC-MD-01 trial ( N = 805) examined patients’ BP using ambulatory BP monitoring (ABPM) and their levels of PRA and plasma aldosterone [ 80 ]. Those examinations revealed that at Week 8, the SPC 10/160 was significantly more effective in lowering ABPM than the component monotherapies valsartan 160 (SBP/DBP; P < 0.001, both) and Neb 10 (DBP; P < 0.01); in addition, the SPC 20/320 reduced 24-h DBP and SBP significantly more than valsartan 320 ( P < 0.01, both) but not Neb 40.…”

“…4 b). A post-hoc analysis with pooled active treatment groups demonstrated a significant correlation between 24-h, daytime, and nighttime ABPM reduction and baseline PRA in participants treated with Neb and SPCs, but not with valsartan; baseline aldosterone levels were correlated with 24-h, daytime, and night-time ABPM reduction in those treated with the SPCs, but not with the monotherapies [ 80 ].…”

“…Neb, nebivolol; PRA, plasma renin activity; SPC, single-pill combination; Val, valsartan. Modified with permission from [ 80 ]. ∗ P < 0.05; ∗∗∗ P < 0.001.…”

Efficacy of nebivolol‐valsartan single‐pill combination in obese and nonobese patients with hypertension

“…Despite this aberration, the nebivolol/valsartan SPC was still more effective than placebo in this group . In spite of nominal reductions in aldosterone levels, especially with the SPCs, aldosterone breakthrough—a phenomenon that affects approximately 30% of individuals receiving RAAS inhibitors—could occur with longer nebivolol‐valsartan treatment. The duration of this study did not allow for this assessment.…”