Beneficial effects on arterial stiffness and pulse-wave reflection of combined enalapril and candesartan in chronic kidney disease--a randomized trial

PLoS One. 2012;7(7):e41757. doi: 10.1371/journal.pone.0041757. Epub 2012 Jul 31.


Background: Cardiovascular disease (CVD) is highly prevalent in patients with chronic kidney disease (CKD). Inhibition of the renin-angiotensinsystem (RAS) in hypertension causes differential effects on central and brachial blood pressure (BP), which has been translated into improved outcome. The objective was to examine if a more complete inhibition of RAS by combining an angiotensin converting enzyme inhibitor (ACEI) and an angiotensin receptor antagonist (ARB) compared to monotherapy has an additive effect on central BP and pulse-wave velocity (PWV), which are known markers of CVD.

Methods: Sixty-seven CKD patients (mean GFR 30, range 13-59 ml/min/1.73 m(2)) participated in an open randomized study of 16 weeks of monotherapy with either enalapril or candesartan followed by 8 weeks of dual blockade aiming at a total dose of 16 mg candesartan and 20 mg enalapril o.d. Pulse-wave measurements were performed at week 0, 8, 16 and 24 by the SphygmoCor device.

Results: Significant additive BP independent reductions were found after dual blockade in aortic PWV (-0.3 m/s, P<0.05) and in augmentation index (-2%, P<0.01) compared to monotherapy. Furthermore pulse pressure amplification was improved (P<0.05) and central systolic BP reduced (-6 mmHg, P<0.01).

Conclusions: Dual blockade of the RAS resulted in an additive BP independent reduction in pulse-wave reflection and arterial stiffness compared to monotherapy in CKD patients.

Trial registration: Clinical NCT00235287.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use*
  • Benzimidazoles / pharmacology
  • Benzimidazoles / therapeutic use*
  • Biphenyl Compounds
  • Blood Pressure / drug effects
  • Cross-Over Studies
  • Drug Therapy, Combination
  • Enalapril / pharmacology
  • Enalapril / therapeutic use*
  • Female
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / etiology
  • Kidney / drug effects
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Pulse Wave Analysis
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / drug therapy*
  • Tetrazoles / pharmacology
  • Tetrazoles / therapeutic use*
  • Vascular Stiffness / drug effects*


  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Benzimidazoles
  • Biphenyl Compounds
  • Tetrazoles
  • Enalapril
  • candesartan

Associated data


Grants and funding

This work is funded by the Danish Kidney Association (Nyreforeningen), the Danish Society of Nephrology, The Danish Heart Association, the Research Council of Herlev Hospital, the Foundations of Augustinus, Hørslev, Aase and Ejnar Danielsen and Aase Bay, Denmark. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.