ISA was singled out in early studies of drug-eluting stents in part over fears that malapposition could affect stent efficacy. By contrast, late ISA hinted that some sort of acute reaction or allergy to the eluted drug was taking place in the tissue. As Degertekin et al explain, other hypotheses have been put forward, including the possibility that ISA is caused by plaque regression, regional positive vascular remodeling, cell necrosis, late dissolution of thrombotic material trapped behind the stent, or cell apoptosis.

"Any dilatation of the vessel lumen raises concern about progressive dilatation over time, aneurysm formation, and ultimately the potential of rupture, as is seen with aortic aneurysms," they note.

In their 13 patients taken from the RAVEL and First-in-Man trials, however, only one patient developed a coronary artery aneurysm (CAA), and the authors believe this single case was in fact a preexisting CAA that had been filled with thrombus at the time of the index procedure that had subsequently resolved. No patients had any symptoms or experienced late thrombotic occlusion, and vessel dimensions and ISA area remained constant over time, with the exception of the one coronary aneurysm.