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Background  In‐stent hyperplasia ( ISH ) may develop in regions of low endothelial shear stress ( ESS ), but the relationship between the magnitude of low  ESS , the extent of  ISH,  and subsequent clinical events has not been investigated.    Methods and Results  We assessed the association of poststent  ESS  with neointimal  ISH  and clinical outcomes in patients treated with percutaneous coronary interventions ( PCI ). Three‐dimensional coronary reconstruction was performed in 374 post‐ PCI  patients at baseline and 6 to 10 months follow‐up as part of the  PREDICTION  Study. Each vessel was divided into 1.5‐mm‐long segments, and we calculated the local  ESS  within each stented segment at baseline. At follow‐up, we assessed  ISH  and the occurrence of a clinically indicated repeat  PCI  for in‐stent restenosis. In 246 total stents (54 overlapping), 100 (40.7%) were bare‐metal stents ( BMS ), 104 (42.3%) sirolimus‐eluting stents, and 42 (17.1%) paclitaxel‐eluting stents. In  BMS , low  ESS  post‐ PCI  at baseline was independently associated with  ISH  (β=1.47 mm 2  per 1‐Pa decrease; 95%  CI , 0.38–2.56;  P <0.01).  ISH  was minimal in drug‐eluting stents. During follow‐up, repeat  PCI  in  BMS  was performed in 21 stents (8.5%). There was no significant association between post‐ PCI ESS  and in‐stent restenosis requiring  PCI .    Conclusions  Low  ESS  after  BMS  implantation is associated with subsequent  ISH .  ISH  is strongly inhibited by drug‐eluting stents. Post‐ PCI ESS  is not associated with in‐stent restenosis requiring repeat  PCI .  ESS  is an important determinant of  ISH  in  BMS , but  ISH  of large magnitude to require  PCI  for in‐stent restenosis is likely attributed to factors other than  ESS  within the stent.

Effects of Low Endothelial Shear Stress After Stent Implantation on Subsequent Neointimal Hyperplasia and Clinical Outcomes in Humans