Saphenous vein grafts (SVGs) have high rates of in-stent restenosis (ISR). We compared the baseline clinical and angiographic characteristics of patients and lesions that did develop ISR with those who did not develop ISR during a median follow-up of 2.7 years in the DIVA study (NCT01121224). We also examined the ISR types using the Mehran classification. ISR developed in 119 out of the 575 DIVA patients (21%), with similar incidence among patients with drug-eluting stents and bare-metal stents (BMS) (21% vs 21%, p = 0.957). Patients in the ISR group were younger (67 ± 7 vs 69 ± 8 years, p = 0.04) and less likely to have heart failure (27% vs 38%, p = 0.03) and SVG lesions with Thrombolysis In Myocardial Infarction 3 flow before the intervention (77% vs 83%, p <0.01), but had a higher number of target SVG lesions (1.33 ± 0.64 vs 1.16 ± 0.42, p <0.01), more stents implanted in the target SVG lesions (1.52 ± 0.80 vs 1.31 ± 0.66, p <0.01), and longer total stent length (31.37 ± 22.11 vs 25.64 ± 17.42 mm, p = 0.01). The incidence of diffuse ISR was similar in patients who received drug-eluting-stents and BMS (57% vs 54%, p = 0.94), but BMS patients were more likely to develop occlusive restenosis (17% vs 33%, p = 0.05).
Drug-eluting stents (DES) reduced the risk of in-stent restenosis (ISR) in native coronary artery lesions compared with bare-metal stents (BMS), yet their role in saphenous vein graft (SVG) percutaneous coronary intervention (PCI) has been controversial. Randomized trials that mandated 6- to 12-month angiographic follow-up showed that BMS had higher rates of angiographic ISR. , However, during long-term follow-up, the 2 largest studies showed no difference in clinical events between DES and BMS, , and another study showed worse outcomes with DES. We compared the clinical, angiographic, and procedural characteristics of patients who did with those who did not develop ISR in the Drug-Eluting Stents in Saphenous Vein Graft Angioplasty (DIVA trial, NCT01121224), a randomized controlled trial conducted at 25 US Department of Veterans Affairs centers. Moreover, we compared the incidence and ISR pattern after DES versus BMS implantation.
DIVA was a prospective, double-blind trial that randomized patients with de novo SVG lesions (50% to 99% stenosis of a 2.25 to 4.5 mm diameter) in a 1:1 ratio to receive either DES or BMS. The vast majority of DES were second generation (88%). The full study protocol and primary results have been published; , patients receiving DES and BMS had similar incidence of the primary endpoint of target vessel failure during a median follow-up of 2.7 years. Nearly all study patients (>99%) were men.
We compared the clinical, angiographic, and procedural characteristics of patients who did with those who did not develop ISR in the DIVA trial. We performed a second analysis comparing the angiographic types of ISR as described by Mehran et al: type IA: lesion ≤10 mm in length at the unscaffolded segment (articulation or gap), type IB: lesion ≤10 mm in length at the proximal or distal margin (but not both), type IC: lesion ≤10 mm in length at the body of the stent, type ID: lesion ≤10 mm in length to both margins (proximal and distal), type II: lesion >10 mm confined to the stent, type III: lesion >10 mm in length that extends beyond the margins of the stent, type IV: total occlusion. Focal ISR includes types IA, IB, IC, and ID, and diffuse ISR includes types II, III, and IV. Repeat angiography was driven by clinical symptoms, and the presence of ISR was indicated by the interventional cardiologist/primary investigator of each center and adjudicated by the core laboratory. Binary ISR was defined as ≥50% angiographic reduction in lumen diameter after stent implantation. Quantitative coronary analysis was performed using the Cardiovascular Angiography Analysis System (version 8.1, Pie Medical Imaging, Maastricht, The Netherlands).
Categorical variables were expressed as percentages and compared using Pearson’s chi-square test or 2-tail Fisher’s exact test. Continuous variables were presented as mean ± SD or median (interquartile range) and were compared using t test or Wilcoxon rank-sum test, as appropriate. Time to event analysis was used to examine the association between use of DES and ISR after adjusting for confounding variables selected on univariable association (p <0.1). SAS 9.2 (TS2M3; SAS Institute, Cary, North Carolina) and R version 3.4.4 were used for the analyses. A two-sided p value of 0.05 was considered statistically significant.
Of the 575 patients who underwent stenting of de novo SVG lesions in the DIVA trial, 119 (21%) developed ISR during a median follow-up of 2.7 years (126 restenotic lesions in 119 grafts, out of 688 treated lesions in 597 grafts). Of note, 58 of 279 patients (21%) with DES and 61 of 296 patients (21%) with BMS developed ISR during the follow-up period (p = 0.89) ( Figure 1 ).
The clinical characteristics of the study patients are summarized in Table 1 . There was no difference in the prevalence of cardiovascular risk factors; however, patients without ISR were more likely to have heart failure. The SVG age was older in the DES group (14.19 ± 6.77 vs 11.56 ± 5.97 years, p = 0.02).
| Variables | Total(N = 688 lesions, 597 grafts, 575 subjects) | No SVG in-stent restenosis(N = 462 lesions, 478 grafts, 456 subjects) | SVG in-stent restenosis(N = 126 lesions, 119 grafts, 119 subjects) | p Value |
|---|---|---|---|---|
| Age * (years) | 68.60 ± 7.56 | 68.93 ± 7.63 | 67.30 ± 7.18 | 0.04 |
| Men | 573 (100%) | 454 (100%) | 119 (100%) | 1.00 |
| White | 498 (89%) | 395 (90%) | 103 (88%) | 0.63 |
| Black | 46 (9%) | 37 (10%) | 9 (8%) | 0.68 |
| Hispanic | 30 (5%) | 24 (5%) | 6 (5%) | 1.00 |
| Body mass index (kg/m 2 ) | 30.51 ± 5.5 | 30.28 ± 5.36 | 31.42 ± 5.96 | 0.13 |
| Years since most recent coronary artery bypass graft surgery | 13.36 ± 6.74 | 13.5 ± 6.81 | 12.84 ± 6.48 | 0.41 |
| Number of narrowed coronary vessels | 0.51 | |||
| 1 | 11 (2%) | 10 (2%) | 1 (1%) | |
| 2 | 54 (9%) | 41 (9%) | 13 (11%) | |
| 3 | 495 (86%) | 391 (86%) | 104 (87%) | |
| First stage chest pain indication for PCI | 0.83 | |||
| Stable angina pectoris | 217 (38%) | 176 (39%) | 41 (34%) | |
| Unstable angina pectoris | 177 (31%) | 140 (31%) | 37 (31%) | |
| Non-STEMI | 135 (23%) | 104 (23%) | 31 (26%) | |
| Other | 46 (8%) | 36 (8%) | 10 (8%) | |
| Hypertension | 553 (96%) | 439 (96%) | 114 (96%) | 0.79 |
| Hyperlipidemia | 559 (97%) | 443 (97%) | 116 (97%) | 1.00 |
| Diabetes mellitus | 345 (60%) | 271 (59%) | 74 (62%) | 0.58 |
| Current smoker | 129 (22%) | 99 (22%) | 30 (25%) | 0.42 |
| Prior myocardial infarction | 304 (53%) | 240 (53%) | 64 (54%) | 0.82 |
| History of atrial fibrillation | 105 (18%) | 85 (19%) | 20 (17%) | 0.64 |
| Congestive heart failure | 204 (35%) | 172 (38%) | 32 (27%) | 0.03 |
| Ejection fraction * | 49.49 ± 13.32 | 48.90 ± 13.52 | 51.87 ± 12.29 | 0.12 |
| Peripheral arterial disease | 103 (18%) | 81 (18%) | 22 (18%) | 0.85 |
The most common target graft recipient vessel was the circumflex/obtuse marginal for both groups (41% vs 40% for no SVG ISR group and SVG ISR group, respectively), followed by the right coronary artery/posterior descending artery (37% vs 34%) and the left anterior descending/diagonal artery (22% vs 25%, p = 0.67 for all comparisons). Furthermore, the location of the SVG target lesion was similar in the no SVG ISR group and the SVG ISR group (21% vs 27%, 70% vs 65% and 9% vs 8% for aortic/ostial, body and coronary anastomosis, p = 0.30 for all comparisons). Lesions in the ISR group patients were less likely to have Thrombolysis In Myocardial Infarction (TIMI) 3 flow before the intervention (83% vs 77%, p <0.01), whereas there was no difference in poststenting TIMI flow between the 2 groups (TIMI 3 flow 98% vs 100%, p = 0.26).
The procedural characteristics of the index procedure are outlined in Table 2 . The ISR group had more target SVG lesions, more stents implanted in target SVG lesions, and longer total stent length. The median highest inflation pressure for the largest balloon in target lesions was similar between the no-ISR and the ISR group (14 [4, 28] vs 12 [5, 24] atmospheres, p = 0.45). On multivariable analysis, only total stent length of all subjects’ target lesions was independently associated with the development of ISR ( Table 3 ).
| Index procedure characteristics | Total(N = 688 lesions, 597 grafts, 575 subjects) | No SVG in-stent restenosis(N = 462 lesions, 478 grafts, 456 subjects) | SVG in-stent restenosis(N = 126 lesions, 119 grafts, 119 subjects) | p Value |
|---|---|---|---|---|
| Arterial access | ||||
| Femoral | 529 (92%) | 419 (92%) | 110 (92%) | 0.87 |
| Radial | 42 (7%) | 33 (7%) | 9 (8%) | |
| Other | 4 (1%) | 4 (1%) | 0 (0%) | |
| Anticoagulant | ||||
| Unfractionated heparin | 332 (58%) | 259 (57%) | 73 (61%) | 0.37 |
| Bivalirudin | 251 (44%) | 200 (44%) | 51 (43%) | 0.84 |
| Glycoprotein IIb/IIIa inhibitor | 84 (15%) | 62 (14%) | 22 (18%) | 0.18 |
| Staged PCI | 64 (11%) | 48 (11%) | 16 (13%) | 0.37 |
| Hemodynamic support During PCI | 4 (1%) | 4 (1%) | 0 (0%) | 0.59 |
| Embolic protection device used in at least 1 target lesion | 410 (71%) | 325 (71%) | 85 (71%) | 0.97 |
| Number of target SVGs intervened per subject * | 1.04 ± 0.19 | 1.04 ± 0.18 | 1.05 ± 0.22 | 0.44 |
| Number of subjects who underwent PCI of more than 1 target SVG lesion | 96 (17%) | 67 (15%) | 29 (24%) | 0.01 |
| Number of target SVG lesions intervened per subject * | 1.20 ± 0.48 | 1.16 ± 0.42 | 1.33 ± 0.64 | <0.01 |
| Number of stents inserted in target SVG lesions per subject * | 1.36 ± 0.70 | 1.31 ± 0.66 | 1.52 ± 0.80 | <0.01 |
| Number of non-target SVG lesions intervened per subject * | 1.37 ± 0.65 | 1.40 ± 0.69 | 1.29 ± 0.46 | 0.72 |
| Type of DES used in target lesions | ||||
| First generation | 23 (4%) | 15 (3%) | 8 (7%) | 0.11 |
| Second generation | 265 (46%) | 210 (46%) | 55 (46%) | 0.97 |
| Total length of stents inserted in target lesions per subject * (mm) | 26.83 ± 18.62 | 25.64 ± 17.42 | 31.37 ± 22.11 | 0.01 |
| Target lesion stent diameter * (mm) | 3.40 ± 0.53 | 3.40 ± 0.53 | 3.37 ± 0.52 | 0.43 |
| Angiographic success | 685 (100%) | 559 (99%) | 126 (100%) | 1.00 |
| Intravascular imaging utilization | ||||
| Intravascular ultrasound | 116 (20%) | 87 (19%) | 29 (24%) | 0.20 |
| Optical coherence tomography | 9 (2%) | 8 (2%) | 1 (1%) | 0.69 |
| Any procedural complication | 31 (5%) | 25 (5%) | 6 (5%) | 0.85 |
| Periprocedural myocardial infarction, n (%) | 28 (5%) | 21 (5%) | 7 (6%) | 0.56 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
