In the present study, we showed that the incidence of ISR after DES implantation in HD patients was 22.4%. Furthermore, a small minimal lumen diameter before DES implantation, a longer lesion length before DES implantation and the use of rotational atherectomy were independent predictors of ISR after DES implantation in patients on HD. PCI is widely performed in HD patients with coronary artery disease4,11). In addition, current guidelines recommend the use of DESs in HD patients7). Since previous studies reported the ISR rate in HD patients in relatively small number of lesions12–20), our present study represents an important contribution to the literature on the angiographic outcomes of PCI in HD patients.
Compared with previous studies in non-HD patients8), we found that the incidence of ISR and MACEs was high in HD patients. In previous reports on ISR rate in HD patients 12–20), the incidence of ISR was 21.2%-39.5% for SES, 13.6% for PES, and 8.7%-16.0% for EES12–20). In the present study, the incidence of ISR for all DESs was 22.4%, which was slightly higher than that reported in previous reports. Although the reasons for the higher rate of restenosis in this study are not clear, the relatively frequent use of rotational atherectomy (31%) and longer lesion length (25.6 ± 13.3 mm) may be involved.
Although this study was not designed to elucidate the mechanisms underlying the high rate of ISR in HD patients, we propose several possible explanations. First, stents in severely calcified lesions are frequently underexpanded and malapposed, which are well-known risk factors for ISR21). Second, calcification and vascular stiffness may cause stent edge dissections and increase the degree of vascular injury, thereby predisposing the lesions to restenosis22). Third, both the number and function of endothelial progenitor cells (EPCs) are reduced in patients with chronic renal failure compared with healthy patients23,24). Furthermore, HD patients tend to have traditional risk factors for coronary arteriosclerosis, such as diabetes and hyperlipidemia. These risk factors also deplete the circulating EPCs and inhibit their functions23,25,26). Because EPCs play a key role in the maintenance of vascular integrity and act as repair cells in response to endothelial injury, reduced number and function of EPCs in HD patients may contribute to higher rate of ISR. Fourth, the activation of the coagulation system, increased platelet aggregability, and the release of oxidant free radicals during dialysis sessions may contribute to the growth of neointimal hyperplasia27).
Predictors for ISR in HD patients at follow-up in this study were a small minimal lumen diameter before DES implantation, a longer lesion length before DES implantation, and the use of rotational atherectomy. These predictors of ISR differ from those in patients with normal renal function. Indeed, the typical risk factors such as diabetes, hypertension, small vessel size, or AHA/ACC type B2/C lesions showed no significant correlation with ISR in this study. A previous study reported that coronary calcification and the use of rotational atherectomy, but not a small minimal lumen diameter or long lesion length before DES implantation, were predictors of target-vessel revascularization19).
The second-generation DESs may be associated with a reduced incidence of ISR compared with the first-generation DESs, as the second-generation DESs have newer polymer coatings and thinner struts. However, in previous studies28,29,30), the incidence of ISR was not significantly different between the first- and the second-generation DESs in non-HD patients. Consistent with those studies, we found that the incidence of ISR was similar between lesions treated with the first-generation DESs (25.8%) and the second-generation DESs (20.4%) in HD patients. Although different types of stents were used in different numbers of lesion in this study, the incidence of ISR was comparable among different stents. Future studies with larger number of lesions will be needed to define the incidence of ISR in different stent types.
Study limitations
Several limitations associated with the present study warrant mention. First, the study was limited by its small sample size, its retrospective nature, and its nonrandomized fashion. Second, all patients were Japanese. A previous study reported that Japanese patients have a better prognosis than subjects in other countries31). This racial prognostic difference should be considered when interpreting our results. Third, this study analyzed lesions with QCA but not with intravascular ultrasound. Although intravascular ultrasound was performed in all patients in this study, the measurements and the actual cross-sectional area obtained on intravascular ultrasound were not considered.