Strut position, blood flow, and drug deposition: implications for single and overlapping drug-eluting stents

Circulation. 2005 Jun 7;111(22):2958-65. doi: 10.1161/CIRCULATIONAHA.104.512475. Epub 2005 May 31.

Abstract

Background: The intricacies of stent design, local pharmacology, tissue biology, and rheology preclude an intuitive understanding of drug distribution and deposition from drug-eluting stents (DES).

Methods and results: A coupled computational fluid dynamics and mass transfer model was applied to predict drug deposition for single and overlapping DES. Drug deposition appeared not only beneath regions of arterial contact with the strut but surprisingly also beneath standing drug pools created by strut disruption of flow. These regions correlated with areas of drug-induced fibrin deposition surrounding DES struts in porcine coronary arteries. Fibrin deposition immediately distal to individual isolated drug-eluting struts was twice as great as in the proximal area and for the stent as a whole was greater in distal segments than proximal segments. Adjacent and overlapping stent struts increased computed arterial drug deposition by far less than the sum of their combined drug load. In addition, drug eluted from the abluminal stent strut surface accounted for only 11% of total deposition, whereas, remarkably, drug eluted from the adluminal surface accounted for 43% of total deposition. Thus, local blood flow alterations and location of drug elution on the strut were far more important in determining arterial wall drug deposition and distribution than were drug load or arterial wall contact with coated strut surfaces.

Conclusions: Simulations that coupled strut configurations with flow dynamics correlated with in vivo effects and revealed that drug deposition occurs less via contact between drug coating and the arterial wall than via flow-mediated deposition of blood-solubilized drug.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arteries / metabolism
  • Arteries / physiology
  • Cardiovascular Agents / administration & dosage*
  • Cardiovascular Agents / pharmacokinetics
  • Computer Simulation
  • Equipment Design
  • Fibrin / metabolism
  • Hemorheology
  • Humans
  • Models, Animal
  • Models, Cardiovascular*
  • Paclitaxel / administration & dosage
  • Paclitaxel / pharmacokinetics
  • Regional Blood Flow
  • Stents*
  • Swine

Substances

  • Cardiovascular Agents
  • Fibrin
  • Paclitaxel