Combined vascular effects of HMG-CoA reductase inhibitor and angiotensin receptor blocker in non-diabetic patients undergoing peritoneal dialysis

Nephrol Dial Transplant. 2011 Nov;26(11):3722-8. doi: 10.1093/ndt/gfr108. Epub 2011 Mar 8.

Abstract

Background: Statins and angiotensin receptor blockers (ARBs) are known to improve vascular dysfunction in patients with chronic kidney disease. However, these effects have been inconsistent in dialysis patients. Moreover, it is currently unknown whether adding statins to ARBs improves vascular dysfunction better than ARB monotherapy in these patients.

Methods: We conducted a prospective open randomized trial to investigate the effects of statin add-on to ARB on vascular protection in 124 nondiabetic patients undergoing peritoneal dialysis (PD). Initially, all patients received 80 mg/day of valsartan for 6 months. Excluding 10 patients who dropped out during this period, patients were randomly assigned to continue ARB treatment alone (n = 57) or to receive 10 mg/day of rosuvastatin (n = 57) added to ARB for the next 6 months. To assess vascular function, endothelium-dependent vasodilation and arterial stiffness were determined by brachial artery flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (baPWV), respectively.

Results: Compared to baseline values, ARB treatment for the first 6 months significantly improved FMD% (2.97 ± 2.64 to 3.57 ± 2.58 %, P < 0.001). In addition, there was a small but significant decrease in baPWV during this period (1691.5 ± 276.3 to 1635.0 ± 278.6 cm/s, P = 0.048). After randomization, add-on treatment further improved FMD% (3.57 ± 2.73 to 4.24 ± 2.77 %, P = 0.003), whereas ARB monotherapy did not (P = 0.02 for between-group difference). Further slight improvement in baPWV (1617.0 ± 280.9 to 1528.9 ± 266.8 cm/s, P = 0.021) was observed only in the combined treatment group (P = 0.28 for between-group difference).

Conclusions: Adding a statin to the ARB was of some help in improving vascular dysfunction more effectively than ARB monotherapy in nondiabetic PD patients. However, whether such limited improvements can lead to better clinical outcomes requires further investigation.

Publication types

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

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Brachial Artery / drug effects*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Peritoneal Dialysis / adverse effects*
  • Prognosis
  • Prospective Studies
  • Tetrazoles / therapeutic use
  • Valine / analogs & derivatives
  • Valine / therapeutic use
  • Valsartan
  • Vascular Resistance / drug effects*
  • Vascular Stiffness / drug effects*
  • Vasodilation / drug effects*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Tetrazoles
  • Valsartan
  • Valine