The Gore TAG Pivotal Trial Results
Repair of descending thoracic aneurysm with the TAG device has shown improved short- and midterm results compared to open repair.
The Gore TAG endoprosthesis (Gore & Associates, Flagstaff, AZ) is the only thoracic endoprosthesis that has gained FDA approval (March 2005) for commercial use for the treatment of descending thoracic aortic aneurysms (Figure 1). Through clinical trials, the safety and efficacy of the TAG endoprosthesis were proven and the midterm results were shown to be superior to those of open repair.
THE GORE TAG DEVICE
The TAG endoprosthesis is made of three layers of expanded polytetrafluoroethylene (ePTFE). It is externally reinforced with ePTFE/FEP (fluorinated ethylene propylene) film and a nitinol self-expanding stent that is fixed with ePTFE/FEP tape to the external surface of the graft. An ePTFE sealing cuff at both ends helps with sealing of the device to the aortic wall. Two radiopaque gold bands at the base of the flares serve as a marker during deployment and in surveillance.
The devices are available in diameters of 26 mm to 40 mm that accommodate aortic diameters between 23 mm and 37 mm. The introducer sheaths that are required are 20 F to 24 F, depending on the device diameter.
US TAG PIVOTAL TRIAL
After device safety was demonstrated with the feasibility study, the pivotal (phase II) trial was undertaken to determine the safety and efficacy of the device for the treatment of descending thoracic aortic aneurysms in comparison with open surgical repair.1,2 The primary efficacy hypothesis was that freedom from any major device-related events at
1 year will be >80% after TAG repair. The efficacy for the open repair was assumed at 100%. The primary endpoint was the percentage of patients free from major device-related events through 1-year follow-up for the TAG group. The secondary endpoints were the operative blood loss, intensive care unit and hospital stay, and recovery-to-baseline activities.
This was a prospective, nonrandomized, controlled study conducted at 17 sites in the US. One hundred forty study patients (140 in the pivotal trial and two in extended access) and 94 control subjects were recruited between September 1999 and May 2001. The surgical control group consisted of two cohorts: 44 prospectively acquired patients and 50 historically acquired patients selected in reverse chronological order. Table 1 shows the inclusion and exclusion criteria.
All patients are to be followed for 5 years with physical examinations and radiological imaging studies consisting of plain films and CT scans at 1-, 6-, and 12-month intervals, and yearly thereafter. Those with primary endoleaks were evaluated at the 3-month visit with a CT scan. A core laboratory reviewed all imaging studies. Clinical data were submitted by individual sites and monitored by sponsor representatives. A clinical events committee adjudicated major adverse events, defined as those that resulted in additional, unintended therapy, increased hospital stay, permanent adversity, or death.3
All major demographic and clinical variables were similar between the two groups. The average age in the TAG group was 71 years, and males constituted 57% of the patients, not unlike those in the control group, whose average age was 68 years and was composed of 51% males. With an exception of higher prevalence of symptomatic aneurysm in the control group, the comorbidities were equivalent between the groups (Table 2). There were no differences in the risk classifications as per American Society of Anesthesiologists classification and the Society for Vascular Surgery risk scores.
Technical success with TAG implantation was achieved in 98% (139 of 142) of the patients. Poor access accounted for all three failures. Conduits were constructed in 21 (15%) patients to provide access. Prophylactic revascularization of the left subclavian artery was performed in 28 (20%) patients who had proximal aneurysms that required coverage of the vessel with the device to ensure proper sealing. One subclavian and one visceral artery were covered unintentionally in one patient each. The latter patient was converted to an open explantation of the device and redeployment of another endograft without an adverse event.
Overall early results were significantly better with TAG repair than with the open repair. Operative mortality (death within 30 days of the procedure or during the same hospitalization) occurred in three patients (2.1%) in the TAG group. A postoperative stroke and a cardiac event accounted for two early deaths. The cause of death in the third patient, who also had an anoxic brain injury from a respiratory arrest, was sepsis from aortoesophageal fistula after 7 months of hospitalization. The mortality rate in the open surgical group was significantly higher at 11.7% (11 of 94; P<.001).
The incidence rates of stroke were similar between the two groups (3.5% TAG vs 4.3% surgical controls; one resulted in death, three were right hemispheric). Notably, in the TAG group, four of the five strokes occurred in patients who had prophylactic left subclavian artery revascularization (four of 28; 14%). This is a significantly higher rate than that observed in those who did not have prophylactic left subclavian artery revascularization (one of 113; 1%; P<.001).
Spinal chord ischemia (SCI), manifested by paraplegia and paraparesis, developed in four patients (2.8%) after TAG repair; in one, paraplegia and paraparesis was immediate and permanent despite all supportive measures. The remaining three cases had delayed onset; all regained motor function (one complete and two partial) and were ambulatory at last follow-up. A significantly higher incidence rate of SCI (13.8%; 13 of 94) was noted in the control group compared to that of the TAG group (P<.001). A history of abdominal aortic aneurysm (AAA) repair did not contribute to an increased incidence of SCI: 4.7% with the history versus 2% without the history. It should be noted that cerebrospinal fluid drainage was not routinely used in either group.
Only intraoperative vascular complication occurred more commonly in the TAG group (14% TAG vs 4% controls). This was caused by passing a large sheath through the iliac arteries. Other common major adverse events (MAEs) were bleeding and cardiopulmonary events, both of which were significantly more frequent in the control group.
A significantly shorter average length of stay in the intensive care unit was noted in the TAG group as compared to the control group (2.6 ± 14.6 days vs 5.2 ± 7.2 days; P<.001). Similarly, the total length of hospital stay was shorter after TAG repair than with open repair
(7.4 ± 17.7 days vs 14.4 ± 12.8 days; P<.001).
Two-year all-cause mortality was 24% in the TAG group and 26% in the surgical control group (Figure 2). The causes of death were commensurate with comorbidities present in this elderly population. There have been no reported ruptures.
Aneurysm-related mortality occurred in one patient with aortoesophageal fistula 2 months after a TAG repair. The patient presented with a graft infection and aneurysm sac enlargement. During open conversion, aortoesophageal fistula was noted, and the endograft was removed followed by an extra-anatomic bypass grafting. Postoperatively, the patient developed respiratory failure and anoxic brain injury and died 1 day later. In the control group, three additional deaths were reported during the first 6 months. No deaths occurred after the first year in either group. Kaplan-Meier estimates of the probability of freedom from aneurysm-related death showed a significant advantage for the TAG group compared with the surgical controls (97% vs 90%; P=.024) at 3 years (Figure 3).
A majority (70%) of the MAEs occurred within 30 days of the original procedure (Table 3). At 1 year, the incidence of MAEs was significantly lower after TAG repair (42%) than after open surgical repair (77%). The same effects were seen through 3-year follow-up. The Kaplan-Meier estimates of the probability of freedom from MAEs at 3 years were 48% in the TAG group and 20% in the surgical control group (Figure 4).
No device-related deaths were noted through 3 years. Stent fractures were reported in 19 patients. Only one patient had an adverse effect (a type II endoleak), which was treated by placement of an additional endograft. Device migrations (three proximal and four components) were noted at a 2-year follow-up without clinical sequelae. At 3-year follow-up, five patients underwent secondary endovascular interventions, and one patient underwent surgical conversion. Sac shrinkage of >5 mm was noted in 38% (24 of 64) of patients, and sac expansion was noted in 17% (11 of 64) of patients. The probability of freedom from device-related events was 94% at 2 years after TAG repair, which is higher than the predefined limit of 80%.
The results of the Gore TAG trials have shown that endovascular treatment of descending thoracic aortic aneurysms is superior to open surgical repair with respect to both short- and midterm results. Operative mortality and morbidity, including the incidence rates of SCI, were lower than those observed with conventional repairs. Device-related complications, aneurysm-related deaths, and major adverse events were all lower than those observed with open repair.
With that said, the device still requires close, life-long surveillance to ensure best long-term outcome, as several limitations have been noted. Aneurysm sac shrinkage, the only surrogate marker for successful repair of aneurysm, is not uniformly achieved.1,4,5 This is not unlike what has been learned from experiences with endovascular repair of AAAs.6,7
Although the incidence rate of spinal cord ischemic injury was lower with repair using the TAG device, it remains a potential source of major morbidity and mortality. Although the Gore pivotal trial did not identify it as a risk factor, previous AAA repair and extensive exclusion of the thoracic aorta portend this devastating complication.8-10
The fact that the strokes were multicentric and right-hemispheric suggests that they were embolic in nature. This reflects potentially dangerous consequences of instrumentation of the aortic arch. This is particularly the case when the aneurysm extends proximally and requires coverage of the left subclavian artery to secure adequate sealing. Planned left subclavian coverage has served as a prognostic indicator for stroke in the pivotal trial, although European experience has suggested no such hazard with it.11
The device still requires a relatively large delivery system, and consequently may cause vascular trauma. This is of particular concern because women comprise approximately 50% of the descending thoracic aorta population. To prevent this problem, conduits should be used as a prophylactic measure rather than as a bail-out procedure. A smaller delivery system would also help reduce this complication.
The Gore TAG US trials have shown safety and efficacy with improved midterm results compared to open surgical repair. Long-term effects are essential to ensure the best outcome. The applicability of this technology to other aortic pathology such as aortic rupture, dissection, and traumatic transection await the results of a high-risk trial that is currently in progress.
Jae-Sung Cho, MD, is Assistant Professor of Surgery, Division of Vascular Surgery at the University of Pittsburgh School of Medicine. He has disclosed that he holds no financial interest in any product or manufacturer mentioned herein. Dr. Cho may be reached at (412) 802-3333; firstname.lastname@example.org.
Michel Makaroun, MD, is Professor and Chief, Division of Vascular Surgery at the University of Pittsburgh School of Medicine. He has disclosed that he serves as a consultant for and receives research support from Gore & Associates. Dr. Makaroun may be reached at (412) 802-3333; email@example.com.
1. Makaroun MS, Dillavou ED, Kee ST, et al. Endovascular treatment of thoracic aortic aneurysms: results of the phase II multicenter trial of the GORE TAG thoracic endoprosthesis. J Vasc Surg. 2005;41:1-9.
2. Cho JS, Haider S, Makaroun MS. US multi-center trials of endoprostheses for the endovascular treatment of descending thoracic aneurysms (DTA). J Vasc Surg. 2006. In press.
3. Sacks D, Marinelli DL, Martin LG, et al. Reporting standards for clinical evaluation of new peripheral arterial revascularization devices. Technology Assessment Committee. J Vasc Interven Radiol. 1997;8(1 Pt 1):137-149.
4. Greenberg RK, O'Neill S, Walker E, et al. Endovascular repair of thoracic aortic lesions with the Zenith TX1 and TX2 thoracic grafts: intermediate-term results. J Vasc Surg. 2005;41:589-596.
5. Ellozy SH, Carroccio A, Minor M, et al. Challenges of endovascular tube graft repair of thoracic aortic aneurysm: midterm follow-up and lessons learned. J Vasc Surg . 2003;38:676-683.
6. Cho JS, Dillavou ED, Rhee RY, et al. Late abdominal aortic aneurysm enlargement after endovascular repair with the Excluder device. J Vasc Surg. 2004;39:1236-1241.
7. Bertges DJ, Chow K, Wyers MC, et al. Abdominal aortic aneurysm size regression after endovascular repair is endograft dependent. J Vasc Surg. 2003;37:716-723.
8. Gravereaux EC, Faries PL, Burks JA, et al. Risk of spinal cord ischemia after endograft repair of thoracic aortic aneurysms. J Vasc Surg. 2001;34:997-1003.
9. Greenberg RK, Resch T, Nyman U, et al. Endovascular repair of descending thoracic aortic aneurysms: an early experience with intermediate-term follow-up. J Vasc Surg. 2000;31:147-156.
10. Moon MR, Mitchell RS, Dake MD, et al. Simultaneous abdominal aortic replacement and thoracic stent-graft placement for multilevel aortic disease. J Vasc Surg. 1997;25:332-340.
11. Gorich J, Asquan Y, Seifarth H, et al. Initial experience with intentional stent-graft coverage of the subclavian artery during endovascular thoracic aortic repairs. J Endovasc Ther. 2002;9(SII):39-43.