Effects of combined treatment with angiotensin II type 1 receptor blocker and statin on stent restenosis

J Cardiovasc Pharmacol. 2009 Feb;53(2):179-86. doi: 10.1097/FJC.0b013e318199f30b.

Abstract

Angiotensin II type I receptor blocker (ARB) or statin has been reported to be effective in preventing stent restenosis, but little is known about the combined effect on stent restenosis. The objective of this study was to determine the effect of combination therapy with ARB and statin on restenosis rate after coronary stenting and on proliferation and migration of and reactive oxygen species (ROS) production by human coronary artery smooth muscle cells (SMCs) in vitro. Clinical data were collected from 330 consecutive patients who underwent coronary stenting for de novo lesions. Six months after stenting, quantitative coronary angiography was performed. Combined therapy with the ARB and statin significantly inhibited stent restenosis (P < 0.05) compared with the effect of the ARB or statin alone. In an in vitro study, platelet-derived growth factor (PDGF)-induced proliferation was significantly inhibited by combined treatment with CV11974, an ARB, and simvastatin (P < 0.01), but the inhibitory effect was not significantly greater than that of simvastatin alone. Migration of human coronary artery SMCs was significantly inhibited by the ARB + statin compared with the effect of the ARB or statin alone (P < 0.01). PDGF-induced production of ROS was also inhibited significantly by the ARB + statin compared with the effect of the ARB or statin alone (P < 0.01). These results indicate that inhibitory effects of combined therapy on PDGF-induced migration of and ROS production by SMCs play an important role in reduction of restenosis rate. Combined treatment with ARB and statin after stenting is useful for preventing stent restenosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Coronary Restenosis / pathology
  • Coronary Restenosis / prevention & control*
  • Coronary Vessels / metabolism
  • Coronary Vessels / pathology
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / pathology
  • Myocytes, Smooth Muscle / physiology
  • Platelet-Derived Growth Factor / metabolism
  • Reactive Oxygen Species / metabolism
  • Retrospective Studies
  • Stents*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Platelet-Derived Growth Factor
  • Reactive Oxygen Species