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

J Am Soc Hypertens. 2015 Nov;9(11):845-54. doi: 10.1016/j.jash.2015.08.003. Epub 2015 Aug 12.


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.

Keywords: ABPM; Vasodilatory beta-blocker; angiotensin II receptor blocker; biomarkers.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / blood
  • Blood Pressure Monitoring, Ambulatory / methods*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension / blood*
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Male
  • Maximum Tolerated Dose
  • Nebivolol / administration & dosage*
  • Patient Selection
  • Renin / blood
  • Renin-Angiotensin System / drug effects*
  • Risk Assessment
  • Severity of Illness Index
  • Treatment Outcome
  • Valsartan / administration & dosage*


  • Nebivolol
  • Aldosterone
  • Valsartan
  • Renin