Diagnosis and treatment of ischemia-producing coronary stenoses improves 5-year survival of patients undergoing major vascular surgery.

OBJECTIVE: Patients undergoing vascular surgery procedures have poor long-term survival due to coexisting coronary artery disease (CAD), which is often asymptomatic, undiagnosed, and undertreated. We sought to determine whether preoperative diagnosis of asymptomatic (silent) coronary ischemia using coronary computed tomography (CT)-derived fractional flow reserve (FFRCT) together with postoperative ischemia-targeted coronary revascularization can reduce adverse cardiac events and improve long-term survival following major vascular surgery METHODS: In this observational cohort study of 522 patients with no known CAD undergoing elective carotid, peripheral, or aneurysm surgery we compared two groups of patients. Group I included 288 patients enrolled in a prospective Institutional Review Board-approved study of preoperative coronary CT angiography (CTA) and FFRCT testing to detect silent coronary ischemia with selective postoperative coronary revascularization in addition to best medical therapy (BMT) (FFRCT guided), and Group II included 234 matched controls with standard preoperative cardiac evaluation and postoperative BMT alone with no elective coronary revascularization (Usual Care). In the FFRCT group, lesion-specific coronary ischemia was defined as FFRCT ≤0.80 distal to a coronary stenosis, with severe ischemia defined as FFRCT ≤0.75. Results were available for patient management decisions. Endpoints included all-cause death, cardiovascular death, myocardial infarction (MI), and major adverse cardiovascular events (MACE [death, MI, or stroke]) during 5-year follow-up. RESULTS: The two groups were similar in age, gender, and comorbidities. In FFRCT, 65% of patients had asymptomatic lesion-specific coronary ischemia, with severe ischemia in 52%, multivessel ischemia in 36% and left main ischemia in 8%. The status of coronary ischemia was unknown in Usual Care. Vascular surgery was performed as planned in both cohorts with no difference in 30-day mortality. In FFRCT, elective ischemia-targeted coronary revascularization was performed in 103 patients 1 to 3 months following surgery. Usual Care had no elective postoperative coronary revascularizations. At 5 years, compared with Usual Care, FFRCT guided had fewer all-cause deaths (16% vs 36%; hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.22-0.60; P < .001), fewer cardiovascular deaths (4% vs 21%; HR, 0.11; 95% CI, 0.04-0.33; P < .001), fewer MIs (4% vs 24%; HR, 0.13; 95% CI, 0.05-0.33; P < .001), and fewer MACE (20% vs 47%; HR, 0.36; 95% CI, 0.23-0.56; P < .001). Five-year survival was 84% in FFRCT compared with 64% in Usual Care (P < .001). CONCLUSIONS: Diagnosis of silent coronary ischemia with ischemia-targeted coronary revascularization in addition to BMT following major vascular surgery was associated with fewer adverse cardiovascular events and improved 5-year survival compared with patients treated with BMT alone as per current guidelines.

Percutaneous Femoropopliteal Bypass: 2-Year Results of the DETOUR System.

PURPOSE: This study investigated the 2-year safety and effectiveness of the PQ Bypass DETOUR system as a percutaneous femoropopliteal bypass. MATERIALS AND METHODS: Seventy-eight patients with 82 long-segment femoropopliteal lesions were enrolled in this prospective, single-arm, multicenter study. The DETOUR system deployed Torus stent grafts directed through a transvenous route. Eligible patients included those with lesions of >10 cm and average of 371±55 mm. Key safety endpoints included major adverse events (MAEs) and symptomatic deep venous thrombosis in the target limb. Effectiveness endpoints included primary patency defined as freedom from ≥50% stenosis, occlusion, or clinically-driven target vessel revascularization (CD-TVR), primary assisted, and secondary patency. RESULTS: Chronic total occlusions and severe calcium occurred in 96% and 67% of lesions, respectively. Core laboratory-assessed total lesion length averaged 371±51 mm with a mean occlusion length of 159±88 mm. The rates of technical and procedural success were 96%, with satisfactory delivery and deployment of the device without in-hospital MAEs in 79/82 limbs. The MAE rate was 22.0%, with 3 unrelated deaths (4%), 12 CD-TVRs (16%), and 1 major amputation (1%). Deep venous thrombosis developed in 2.8% of target limbs, and there were no reported pulmonary emboli. Primary, assisted primary, and secondary patency rates by the Kaplan-Meier analysis were 79±5%, 79±5%, and 86±4%, respectively. CONCLUSIONS: The PQ Bypass DETOUR system is a safe and effective percutaneous alternative to femoropopliteal open bypass with favorable results through 2 years. The DETOUR system provides a durable alternative to conventional endovascular modalities and open surgery for patients with long, severely calcified, or occluded femoropopliteal lesions.

Low-dose rivaroxaban plus aspirin in older patients with peripheral artery disease undergoing acute limb revascularization: insights from the VOYAGER PAD trial.

AIMS: In this secondary analysis of the VOYAGER trial, rivaroxaban 2.5 mg twice/day plus aspirin 100 mg/day was assessed in older adults. Advanced age is associated with elevated bleeding risk and unfavourable net benefit for dual antiplatelet therapy in chronic coronary artery disease. The risk-benefit of low-dose rivaroxaban in patients ≥75 years with peripheral artery disease (PAD) after lower extremity revascularization (LER) has not been described. METHODS AND RESULTS: The primary endpoint was a composite of acute limb ischaemia, major amputation, myocardial infarction, ischaemic stroke, or cardiovascular death. The principal safety outcome was thrombolysis in myocardial infarction (TIMI) major bleeding analysed by the pre-specified age cut-off of 75 years. Of 6564 patients randomized, 1330 (20%) were >75 years. Absolute 3-year Kaplan-Meier cumulative incidence rates for primary efficacy (23.4% vs. 19.0%) and safety (3.5% vs. 1.5%) endpoints were higher in elderly vs. non-elderly patients. Efficacy of rivaroxaban (P-interaction 0.83) and safety (P-interaction 0.38) was consistent irrespective of age. The combination of intracranial and fatal bleeding was not increased in patients >75 years (2 rivaroxaban vs. 8 placebo). Overall, benefits (absolute risk reduction 3.8%, number needed to treat 26 for the primary endpoint) exceeded risks (absolute risk increase 0.81%, number needed to harm 123 for TIMI major bleeding). CONCLUSION: Patients ≥75 years with PAD are at both heightened ischaemic and bleeding risk after LER. No excess harm with respect to major, intracranial or fatal bleeding was seen in older patients yet numerically greater absolute benefits were observed. This suggests that low-dose rivaroxaban combined with aspirin should be considered in PAD after LER regardless of age.

Venous outcomes at 1 year after using the femoral vein as a conduit for passage of percutaneous femoropopliteal bypass.

OBJECTIVE: The DETOUR 1 study was performed to assess the safety of the femoral vein as a "pass through" conduit for covered stent placement during fully percutaneous femoropopliteal bypass, also known as the DETOUR procedure. METHODS: At eight participating centers in this prospective, single-arm, international trial, 78 patients (82 femoropopliteal lesions) were enrolled. All patients had patent femoral veins measuring ≥10 mm in diameter at baseline. The DETOUR procedure involved delivery of a series of TORUS stent grafts, deployed from contralateral common femoral artery access, to the ipsilateral proximal superficial femoral artery, with entry into the femoral vein and re-entry into the arterial vasculature at the above-the-knee popliteal artery. The TORUS stent grafts are deployed in an overlapping configuration as an arterial-arterial conduit. Due to this novel transvenous approach, we assessed specific considerations related to the venous system to analyze the risk of risk of venous thromboembolic complications. Symptomatic deep vein thrombosis, nonocclusive material associated with the graft such as benign endovenous graft-associated material, pulmonary embolism, Venous Clinical Severity Score (VCSS) and Villalta scores, and luminal occupancy by the stent graft were assessed as the ratio of cross-sectional areas of the stent graft to the native vein at baseline and 1 year after the procedure. RESULTS: A duplicate femoral vein was present in 20.7% of cases. The majority of patients (86.8%) had a femoral vein luminal area preservation of ≥55%. Thirty-two patients experienced an increase in the vein diameter over time after the procedure, but this pattern of venous remodeling was not uniform. The patients who had a compensatory increase in the vein diameter had a smaller average baseline vein diameter compared with the patients who did not have a compensatory increase in vein diameter (P = .0414). Only two patients (2.4%) developed ipsilateral symptomatic deep vein thrombosis) through 1 year of follow-up. There were no pulmonary embolism in any patient in the series. The overall VCSS and Villata scores did not change during follow-up. Mean VCSS and Villata were 0.8 ± 1.4 and 0.5 ± 1.1 at 1 year, compared with 0.6 ± 1.0 and 0.4 ± 0.9 at baseline, respectively. CONCLUSIONS: As a percutaneous alternative to open surgical bypass for complex femoropopliteal peripheral arterial disease, the transvenous bypass has a low rate of deep venous thrombotic and obstructive complications. Cross-sectional vein area is preserved, and in some patients, the compensatory vein diameter increases with time, supporting the feasibility and safety of using the lower extremity deep venous system as a pass-through conduit for the DETOUR percutaneous femoropopliteal bypass. TRIAL REGISTRATION: NCT02471638.

One-year results from the DETOUR I trial of the PQ Bypass DETOUR System for percutaneous femoropopliteal bypass.

OBJECTIVE: The objective of this study was to evaluate the 1-year safety and effectiveness outcomes associated with the PQ Bypass DETOUR System (PQ Bypass, Milpitas, Calif) for the percutaneous bypass of long-segment femoropopliteal occlusive disease. METHODS: This prospective, single-arm, multicenter trial enrolled patients with long-segment femoropopliteal arterial disease. The DETOUR System percutaneously deploys modular stent grafts to bypass femoropopliteal lesions through a transvenous route. Eligible patients included those with TransAtlantic Inter-Society Consensus C and D lesions >100 mm in length. The primary safety end point was the major adverse event (MAE) rate through 1 month, defined as the composite of death, clinically driven target vessel revascularization (CD-TVR), or major amputation. The primary effectiveness end point was stent graft patency through 6 months, defined as freedom from stenosis ≥50%, occlusion, or CD-TVR. RESULTS: During a 24-month period, 78 patients (82 limbs) were enrolled. The average core laboratory-measured lesion length was 371 ± 55 mm; 79 of 82 lesions (96%) were chronic total occlusions, and 55 of 82 lesions (67%) had severe calcification. The rates of technical and procedural success measured during the index procedure were both 96%, with satisfactory delivery and deployment of the device without MAEs in 79 of 82 limbs. Through 1 month, there were no deaths or amputations; CD-TVRs occurred in 2 of 81 limbs (3%), and freedom from MAEs was 98% (79/81). The 1-year Kaplan-Meier primary, assisted primary, and secondary patency rates were 81% ± 4%, 82% ± 4%, and 90% ± 3%, respectively. The ankle-brachial index increased an average of 0.25 ± 0.27 between baseline and 1 year (P < .001). Through 1 year, the Kaplan-Meier estimates of freedom from stent graft thrombosis, CD-TVR, and MAE were 84% ± 4%, 85% ± 4%, and 84% ± 4%, respectively. At 1 year, the Rutherford class improved in 77 of 80 limbs (96%), and 65 of 80 (81%) were asymptomatic. Deep venous thrombosis developed in 2 of 79 target limbs (3%) through 1 year, both at the femoropopliteal vein level. There were no instances of pulmonary embolism. CONCLUSIONS: The 1-year results from the DETOUR I trial show that the PQ Bypass DETOUR System is a safe and effective percutaneous treatment option for patients with longer, severely calcified, above-knee femoropopliteal lesions.

Rivaroxaban in Peripheral Artery Disease after Revascularization.

BACKGROUND: Patients with peripheral artery disease who have undergone lower-extremity revascularization are at high risk for major adverse limb and cardiovascular events. The efficacy and safety of rivaroxaban in this context are uncertain. METHODS: In a double-blind trial, patients with peripheral artery disease who had undergone revascularization were randomly assigned to receive rivaroxaban (2.5 mg twice daily) plus aspirin or placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes. The principal safety outcome was major bleeding, defined according to the Thrombolysis in Myocardial Infarction (TIMI) classification; major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH) was a secondary safety outcome. RESULTS: A total of 6564 patients underwent randomization; 3286 were assigned to the rivaroxaban group, and 3278 were assigned to the placebo group. The primary efficacy outcome occurred in 508 patients in the rivaroxaban group and in 584 in the placebo group; the Kaplan-Meier estimates of the incidence at 3 years were 17.3% and 19.9%, respectively (hazard ratio, 0.85, 95% confidence interval [CI], 0.76 to 0.96; P = 0.009). TIMI major bleeding occurred in 62 patients in the rivaroxaban group and in 44 patients in the placebo group (2.65% and 1.87%; hazard ratio, 1.43; 95% CI, 0.97 to 2.10; P = 0.07). ISTH major bleeding occurred in 140 patients in the rivaroxaban group, as compared with 100 patients in the placebo group (5.94% and 4.06%; hazard ratio, 1.42; 95% CI, 1.10 to 1.84; P = 0.007). CONCLUSIONS: In patients with peripheral artery disease who had undergone lower-extremity revascularization, rivaroxaban at a dose of 2.5 mg twice daily plus aspirin was associated with a significantly lower incidence of the composite outcome of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes than aspirin alone. The incidence of TIMI major bleeding did not differ significantly between the groups. The incidence of ISTH major bleeding was significantly higher with rivaroxaban and aspirin than with aspirin alone. (Funded by Bayer and Janssen Pharmaceuticals; VOYAGER PAD ClinicalTrials.gov number, NCT02504216.).

Preservation of hypogastric flow and control of iliac aneurysm size in the treatment of aortoiliac aneurysms using the Nellix EndoVascular Aneurysm Sealing endograft.

OBJECTIVE: The purpose of this study was to determine the long-term effectiveness of endovascular aneurysm sealing (EVAS) in the treatment of complex aortoiliac aneurysms with preservation of hypogastric artery flow. METHODS: We reviewed all patients with abdominal aortic aneurysms (AAAs) and common iliac aneurysms (CIAs) enrolled and treated in prospective studies of EVAS using the Nellix endograft (Endologix, Irvine, Calif) at two centers from 2008 to 2014. Patients with 1 year or more of computed tomography follow-up underwent quantitative morphometric assessment by two independent vascular radiologists blinded to clinical outcome results. Hypogastric patency and CIA diameter changes over time were assessed and compared in three treatment groups: totally excluded CIA, partially excluded CIA, and untreated CIA. RESULTS: Among 125 patients with EVAS, 68 patients (mean age, 75 ± 8 years; 79% men) had both AAA (mean diameter, 55.8 ± 2.0 mm) and CIA (median diameter, 23.4; interquartile range, 21.3-27.0 mm), with bilateral CIAs in 33 patients. Treatment of 101 CIAs included complete CIA exclusion in 40 (39.6%), partial CIA exclusion in 33 (32.7%), and no CIA treatment in 28 (27.7%), with successful AAA exclusion in all patients. Internal iliac flow was preserved in all 122 hypogastric arteries that were patent before treatment (14 hypogastric arteries were occluded at baseline). During the 5-year follow-up period (median follow-up, 24.7 months; range, 11.5-61.7 months), three patients required secondary treatment with hypogastric occlusion and graft extension to the external iliac. Thus, internal iliac flow was maintained in 98% of at-risk hypogastric arteries. There were no aneurysm-related clinical events, except for the three secondary treatments. Totally excluded iliac aneurysms did not change in diameter over time (P = .85), whereas untreated CIAs enlarged at a rate of 0.16 mm/y (95% confidence interval, 0.09-0.23; P < .0001). Partially excluded CIAs enlarged at a higher rate of 0.59 mm/y (95% confidence interval, 0.47-0.71; P < .0001). Enlargement ≥3 mm occurred only in partially treated CIAs larger than 3 cm. CONCLUSIONS: EVAS was effective in treating aortoiliac aneurysms with preservation of internal iliac patency in most cases. Complete CIA exclusion prevented aneurysm enlargement over time, whereas partial exclusion did not prevent continued CIA enlargement, particularly in larger aneurysms.

Initial clinical experience with a sac-anchoring endoprosthesis for aortic aneurysm repair.

OBJECTIVE: All current aortic endografts depend on proximal and distal fixation to prevent migration. However, migration and rupture can occur, particularly in patients with aortic necks that are short or angulated, or both. We present our initial clinical experience with a new sac-anchoring endoprosthesis designed to anchor and seal the device within the aneurysm sac. METHODS: The initial worldwide experience using a new endoprosthesis for the treatment of aortic aneurysms (Nellix Endovascular, Palo Alto, Calif) was reviewed. The endoprosthesis consists of dual balloon-expandable endoframes surrounded by polymer-filled endobags designed to obliterate the aneurysm sac and maintain endograft position. Clinical results and follow-up contrast computed tomography (CT) scans at 30 days and 6 and 12 months were reviewed. RESULTS: The endograft was successfully deployed in 21 patients with infrarenal aortic aneurysms measuring 5.7 ± 0.7 cm (range, 4.3-7.4 cm). Two patients with common iliac aneurysms were treated with sac-anchoring extenders that maintained patency of the internal iliac artery. Infusion of 71 ± 37 mL of polymer (range, 19-158 mL) into the aortic endobags resulted in complete aneurysm exclusion in all patients. Mean implant time was 76 ± 35 minutes, with 33 ± 17 minutes of fluoroscopy time and 180 ± 81 mL of contrast; estimated blood loss was 174 ± 116 mL. One patient died during the postoperative period (30-day mortality, 4.8%), and one died at 10 months from non-device-related causes. During a mean follow-up of 8.7 ± 3.1 months and a median of 6.3 months, there were no late aneurysm- or device-related adverse events and no secondary procedures. CT imaging studies at 6 months and 1 year revealed no increase in aneurysm size, no device migration, and no new endoleaks. One patient had a limited proximal type I endoleak at 30 days that resolved at 60 days and remained sealed. One patient has an ongoing distal type I endoleak near the iliac bifurcation, with no change in aneurysm size at 12 months. CONCLUSION: Initial clinical experience with this novel intrasac anchoring prosthesis is promising, with successful aneurysm exclusion and good short-term results. This new device platform has the potential to address the anatomic restrictions and limitations of current endografts. Further studies with a longer follow-up time are needed.