Objectives: The pivotal trial of the Talent enhanced Low Profile System (eLPS; Medtronic Vascular, Santa Rosa, Calif) stent graft evaluated short and long-term safety and efficacy of endovascular aneurysm repair (EVAR). These data and a confirmatory group assessing the performance of the CoilTrac delivery system supported the United States premarket approval application for the device.Methods: The pivotal trial was a prospective, nonrandomized study conducted at 13 sites from February 2002 to April 2003. The study group (n = 166) underwent EVAR using the Talent eLPS stent graft. The control group (n = 243) underwent open surgical AAA repair. Data for this group were obtained from the Society for Vascular Surgery Endovascular AAA Surgical Controls project. Outcomes were compared at 30 days and 12 months. Additional 5-year follow-up was obtained for the eLPS group. A single-center cohort of 137 patients was the confirmatory group for the assessment of the clinical performance of the CoilTrac delivery system, with analysis of outcomes ≤30 days from the procedure.Results: AAA anatomy with neck length as short as 3 mm and maximum neck diameter of 32 mm were included in the eLPS group. EVAR was superior to open repair for periprocedural outcomes, including mean procedure duration (167.3 vs 196.4 minutes, P < .001), blood transfusion (18.2% vs 56.8%, P < .001), median intensive care unit stay (19.3 vs 74.3 hours, P < .001), and mean hospital stay (3.6 vs 8.2 days, P < .001). Freedom from major adverse events was 89.2% for EVAR at 30 days vs 44.0% (P < .001) and 81.3% vs 42.4% at 1 year (P < .001). Freedom from all-cause mortality and aneurysm-related mortality (ARM) was 93.7% and 98.2% for EVAR vs 92.4% and 96.7% for the controls. Through 5 years for the EVAR group, rates of freedom from all-cause mortality, ARM, aneurysm rupture, and conversion to surgery were 69.8%, 96.5%, 98.2%, and 99.1%, respectively, with one conversion to surgery, 25 secondary reinterventions, and five site-reported instances of stent graft migration. The technical success rate for the CoilTrac confirmatory group was 100%, with no aneurysm rupture or conversion to open repair at 30 days. The 30-day all-cause mortality rate was 1.5% (2 of 137).Conclusions: In a population with challenging anatomic characteristics, EVAR with the Talent eLPS and use of the CoilTrac delivery system compared favorably with open repair through 1 year. Sustained protection from ARM, with minimal reinterventions, was attained through 5 years.

Objectives: Blunt carotid injury (BCI) is uncommon but potentially devastating. The best treatment modality for this injury remains undetermined. We conducted this study to better understand the hospital course and treatment outcomes for patients with BCI who received different interventions.Methods: BCI and related vascular procedures were identified by ICD-9-CM codes from the National Trauma Data Bank using data gathered from 2002 to 2006. Conservative and operative treatment groups were compared by variables of patient demographics, initial assessment in the emergency department (ED), hospital course, and treatment outcomes. Open surgical and endovascular interventions were further compared.Results: A total of 842 BCI were identified from 1,633,126 discharged blunt trauma patients (0.05%). Of these, 762 (90.5%) were treated conservatively and 80 (9.5%) received operative intervention. No differences in demographics were observed between these treatment groups. On initial assessment, no differences between conservative and operative treatment groups were noted with regard to vital signs, Glasgow coma scale, presence of drugs or alcohol in blood, or Trauma Related Injury Severity Score survival probability. Significant differences were seen in terms of the presence of a base deficit (−3.1 ± 6.8 vs −7.6 ± 8.3; P = .01), likelihood of a positive head computed tomography (CT) scan (58.6% vs 26.1%; P = .003), and total Injury Severity Score (29.8 ± 13.3 vs 26.1 ± 14.1; P = .02). Hospital course and treatment outcomes were comparable, with no differences in hospital length of stay (13.4 ± 15.3 days vs 13.7 ± 13.6 days; P = .86), total Functional Independence Measure (8.8 ± 3.3 vs 9.3 ± 3.1; P = .38), progression of original neurologic insult (7.5% vs 4.6%; P = .61) or mortality (28.1% vs 19%; P = .08). When comparing open surgical to endovascular interventions (46 open, 34 endovascular, including 3 combined), the only significant differences were in the total Injury Severity Score (22.4 ± 12.2 vs 31.4 ± 15.4; P = .01) and length of intensive care unit (ICU) and hospital stay (5.0 ± 6.0 days vs 10.7 ± 10.4 days; P = .01, and 10.3 ± 9.2 days vs 19.3 ± 17.7 days; P = .01). Multivariate regression analysis confirmed that neither Functional Independence Measure (FIM) nor mortality was associated with conservative or operative treatment.Conclusion: BCI is rare and carries a poor prognosis. Operative intervention is not associated with functional improvement or a survival advantage. This study was unable to support that less invasive endovascular treatment improves treatment outcome when compared to open surgery.

The publication of a randomized controlled trial in the vascular arena is rare. The publication of a trial with negative results is rarer. Han and colleagues should be applauded for an honest portrayal of the use of alfimeprase in the setting of acute limb ischemia (ALI). Alfimeprase, a novel recombinant variant of fibrolase, displayed promising results in preclinical and pilot studies. In contrast to available thrombolytic agents, alfimeprase is a direct fibrinolytic enzyme and has no effect on plasminogen. In addition, any drug that escapes into the general circulation is quickly degraded by α2-macroglobulin which is ubiquitous in plasma. These properties have the potential to overcome limitations that exist with current therapies: the duration of therapy and the risk of bleeding. A rapidly-acting, direct fibrinolytic without systemic plasminogen activation and plasma neutralization seem like ideal characteristics for a thrombolytic agent. In this report, data from two essentially blinded, placebo-controlled, randomized controlled trials evaluating alfimeprase for ALI are reported. Alas, alfimeprase showed no greater effectiveness than placebo in ALI patients with mostly femoral/popliteal thrombus in native arteries. In fact, the rates of distal embolization and amputation in the treatment groups were troubling.

Objective: To assess the gender and ethnic differences in arterial compliance in patients with intermittent claudication.Methods: A total of 114 patients participated, including 38 Caucasian men, 32 Caucasian women, 16 African American men, and 28 African American women. Patients were assessed on large artery elasticity index (LAEI), small artery elasticity index (SAEI), age, weight, body mass index, ankle-brachial index (ABI), smoking status, and metabolic syndrome components.Results: Group differences were found for LAEI (P = .042), SAEI (P = .019), body mass index (P = .020), prevalence of elevated fasting glucose (P = .001), and prevalence of abdominal obesity (P = .025). Significant covariates for LAEI included age (P = .0002) and elevated triglycerides (P = .0719). LAEI (units = 10 mL × mm Hg) adjusted for age and triglycerides was 39% lower (P = .0005) in African Americans (11.4 ± .90; mean ± SE) than in Caucasians (15.8 ± 0.72), whereas no significant difference (P = .7904) existed between men (13.8 ± 0.81) and women (13.5 ± 0.79). Significant covariates for SAEI included age (P = .0001), abdominal obesity (P = .0030), and elevated blood pressure (P = .0067). SAEI (units = 100 mL × mm Hg) adjusted for age, abdominal obesity, and elevated blood pressure was 32% lower (P = .0007) in African-Americans (2.8 ± 0.3) than in Caucasians 4.1 ± 0.2), and was 18% lower (P = .0442) in women (3.1 ± 0.2) than in men (3.8 ± 0.2).Conclusion: African American patients with intermittent claudication have more impaired macrovascular and microvascular function than Caucasian patients, and women have more impaired microvascular function than men. These ethnic and gender differences in arterial compliance are evident even though ABI was similar among groups, suggesting that arterial compliance provides unique information to quantify vascular impairment in patients with intermittent claudication.

Background: Current medical practice urges individual health care facilities and medical professionals to obtain and provide detailed insight in quality of care with the possibility of comparing data between institutions. Adverse event (AE) analysis serves as a mainstay in quality assessment in vascular surgery, but the comparison of AE data between facilities can be complex. The aim of the present study was to assess independent risk factors for AE occurrence: patient, disease and operation characteristics besides general differences between health care facilities.Methods: All AEs after infrainguinal bypass graft procedures (BGPs) in three health care facilities in the Netherlands were evaluated. AEs were defined identically in the facilities.Results: Of 601 BGPs performed, 662 AEs were registered. Independent predictors of AEs were female gender (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.39-3.26; P < .01), age ≥60 years (OR, 0.57; 95% CI, 0.34-0.95; P = .03), American Society of Anesthesiologists classification 3-4 (OR, 1.79; 95% CI, 1.01-3.17; P = .05), comorbidities of pulmonary disease (OR, 2.99; 95% CI, 1.67-5.34; P < .01) and diabetes mellitus (OR, 2.49; 95% CI, 1.58-3.94; P < .01), distal anastomosis level at below knee femoropopliteal BGP (OR, 2.01; 95% CI, 1.26-3.22; P < .01), femorotibial BGP (OR, 2.40; 95% CI, 1.37-4.19; P < .01), and popliteopedal BGP (OR, 92.39; 95% CI, 11.13-766.98; P < .01). One health care facility had significantly fewer AEs than the other two (OR, 0.21; 95% CI, 0.13-0.35; P < .01).Conclusion: Age, gender, comorbidity, and type of surgery are all independent predictors of AE occurrence in vascular surgery. After adjustment for differences in these factors, one health care facility still had lower AE occurrence, which needs to be examined further.

Purpose: To determine the walking economy before and after the onset of claudication pain in patients with peripheral arterial disease (PAD), and to identify predictors of the change in walking economy following the onset of claudication pain.Methods: A total of 39 patients with PAD were studied, in which 29 experienced claudication (Pain group) during a constant load, walking economy treadmill test (speed = 2.0 mph, grade = 0%) and 10 were pain-free during this test (Pain-Free group). Patients were characterized on walking economy (ie, oxygen uptake during ambulation), as well as on demographic characteristics, cardiovascular risk factors, baseline exercise performance measures, and the ischemic window calculated from the decrease in ankle systolic blood pressure following exercise.Results: During the constant load treadmill test, the Pain group experienced onset of claudication pain at 323 ± 195 seconds (mean ± standard deviation) and continued to walk until maximal pain was attained at 759 ± 332 seconds. Walking economy during pain-free ambulation (9.54 ± 1.42 ml·kg−1·min−1) changed (P < .001) after the onset of pain (10.18 ± 1.56 ml·kg−1·min−1). The change in walking economy after the onset of pain was associated with ischemic window (P < .001), hypertension (P < .001), diabetes (P = .002), and height (P = .003). In contrast, the Pain-Free group walked pain-free for the entire 20-minute test duration without a change in walking economy (P = .36) from the second minute of exercise (9.20 ± 1.62 ml·kg−1·min−1) to the nineteenth minute of exercise (9.07 ± 1.54 ml·kg−1·min−1).Conclusion: Painful ambulation at a constant speed is associated with impaired walking economy, as measured by an increase in oxygen uptake in patients limited by intermittent claudication, and the change in walking economy is explained, in part, by severity of PAD, diabetes, and hypertension.

Objectives: This study used air plethysmographic parameters to evaluate the changes in venous hemodynamics after the surgical treatment of primary varicose veins.Methods: We retrospectively analyzed 1756 limbs of 1620 patients who had undergone surgery for great saphenous vein (GSV) reflux from January 1996 to June 2009 at Samsung Medical Center. Venous hemodynamic changes were evaluated by performing air plethysmography preoperatively and 1 month postoperatively and assessing the venous volume (VV), the venous filling index (VFI), the residual volume fraction (RVF), and the ejection fraction (EF).Results: Preoperatively, median (interquartile range) values were VV, 121.6 (94.7-160.6) mL; VFI, 4.8 (2.9-7.6) mL/s; RVF, 40.6% (29.7%-50.0%); and EF, 53.5% (44.3%-64.1%). Postoperatively, the median (interquartile range) values were VV, 90.6 (69.1-116.8) mL; VFI, 1.4 (0.9-1.9) mL/s; RVF, 28.4% (17.5%-38.7%); and EF, 65.2% (54.5%-77.2%). VV, VFI, and RVF were reduced 25.2%, 71.5%, and 29.9%, respectively; EF was increased 20.3%. The results were significant for all four variables (P < .001). We compared the degree of hemodynamic changes according to the treatment modalities: the high ligation and stripping group , 1578 cases; the GSV valvuloplasty group, 124 cases; and the VNUS group (VNUS Medical Technologies Inc, San Jose, CA), 54 cases. The reduction of the VV, VFI, and RVF was greater in the GSV stripping group and in the VNUS group than in the valvuloplasty group (P < .001), yet no difference was noted in the EF increase among the surgical modalities (P = .157).Conclusion: Our results show that the venous hemodynamic parameters of primary varicose veins were improved after surgical treatment.

Sexual steroid hormones are known to influence the endothelial function of blood vessels. Several studies have shown an association between increased levels of estradiol and varicose veins in women. Also, the effect of pregnancy in the diameter of the veins and the development of reflux and varicose veins has been demonstrated. Until the current study, few reports suggested a possible association between sexual steroid hormones and varicose veins in males. The important finding in this report is that estradiol and testosterone serum levels were higher in refluxing veins of the lower extremities when compared to those from the arm veins of the same patients. It is also interesting that the serum levels of estradiol and testosterone were significantly higher in lower extremities than the upper extremities in the control group. No difference was detected in the hemoglobin, platelets, and white blood cell count in neither group nor the extremities. There were 20 patients and 20 controls. Of the 20 patients, only 2 were in class 2 and 2 had ulceration, while 9 had swelling and 7 had skin discoloration. Obviously with this low number in each CEAP class, and many other factors being present, it is difficult to make any solid conclusions. For example, it would have been nice to have all 20 patients in class 2. In this way, the patients were likely to be younger which would match the age of the control group. Despite the limitations in the design of the study, the findings deserve great attention as they point out that local hormone regulation may be associated with the development of varicose veins. A larger sample representing all the CEAP classes in adequate numbers would have been ideal. The authors have clearly described the limitations of the study and report their findings as a pilot data, which is appropriate. They also concluded that further clinical and laboratory work is needed. Sexual hormones are known to modify the synthesis and/or the bioactivity of NO, PGI2, endothelium-derived hyperpolarizing factor (EDHF), and the endothelium-derived contracting factors. These functions have an effect on the contractility and relaxation of the vascular smooth muscle. Multiple reports have shown that sexual hormone receptors are expressed both on the endothelium and the vascular smooth muscle. Gender differences on the contractility of the vascular smooth muscle have also been well documented in animal models. However, the sexual hormone receptor subtypes, distribution, and the way by which they affect the function of the vascular cells needs to be investigated further.

Objective: Smoking is a major risk factor for peripheral arterial disease (PAD), and PAD is associated with all-cause and cardiovascular disease (CVD) mortality. The objective of this study was to determine the combined effects of smoking and PAD on all-cause and CVD mortality.Methods: A total of 1979 males 35 years of age or older were enrolled from eight university-affiliated hospitals in Beijing and Shanghai in 2004, with both smoking status and PAD diagnosis obtained, 1712 of them had complete follow-up data. Mortality data were obtained from all participants between December 2007 and February 2008. Cox proportional hazards models were used to evaluate relative risks (RRs) of all-cause mortality and CVD mortality among different groups.Results: At baseline, the average age of participants was 66.98-years-old (SD = 11.57), prevalence of PAD was 24.0% and 65.4% smoked cigarettes. During the 3-year follow-up, all-cause cumulative mortality rates were 27.9% (PAD/smoker), 26.3% (PAD/nonsmoker), 14.1% (no PAD/smoker), and 14.4% (no PAD/nonsmoker) (P < .001), and CVD cumulative mortality rates were 17.8%, 14.9%, 8.1%, and 7.3%, respectively (P < .001). Compared with the no PAD/nonsmoker subjects, adjusted RR from all-cause mortality in the groups of both PAD/smoker, PAD/nonsmoker, and no PAD/smoker were 1.88 (95% confidence interval [CI], 1.34-2.64), 1.37 (95% CI, 0.85-2.23), and 1.08 (95% CI, 0.79-1.49), respectively. The adjusted RR from CVD mortality was 2.12 (95% CI, 1.37-3.28), 1.55 (95% CI, 0.84-2.86), and 1.13 (95% CI, 0.74-1.71), respectively.Conclusion: PAD is a major determinant of mortality. Smoking did not contribute to mortality in this study. Further research is needed.

Objective: In principle, superiority of computational wall stress analyses compared with the maximum diameter criterion for rupture risk evaluation of abdominal aortic aneurysm (AAA) has been demonstrated. The results of finite element analyses should be evaluated carefully, however, because computational strains and stresses are highly dependent on the quality and complexity of each step of AAA simulation. Most clinically active vascular specialists are not familiar with the processes of computational mechanics to evaluate the quality of AAA simulations. For better understanding and to provide insights in computational biomechanics of AAA, the effect of different computational model assumptions on the results of simulation are explained and demonstrated.Methods: Four patients with asymptomatic (n = 3) and symptomatic (n = 1) infrarenal AAAs with distinctly different aneurysm morphologies were exemplarily studied. For segmentation and 3-dimensional (3D) reconstruction of AAA and thrombus, 3-mm computed tomography (CT) slices were used, and a high-density hexahedral element-dominated finite element mesh was generated. Subsequent AAAs were simulated on seven different levels, culminating in the most realistic ortho-pressure–finite element analyses simulations, including thrombus, wall calcifications, and prestress state of AAA geometry with nonlinear hyperelastic material and geometric model assumptions.Results: Alterations in displacements due to model assumptions are up to 740% for a specific aneurysm. The average maximum discrepancy among the four morphologies between simple and advanced models is 607%. Differences in peak wall stress between simple and realistic models are up to 210% individually and 170% on average.Conclusion: Differences of model assumptions are more important for simulation results than differences between patient-specific morphologies. Because the biomechanical behavior of AAA is nonlinear in many senses, comparisons between individual morphologies and statistics are only valid when detailed information about preconditions and model assumptions is provided.Clinical Relevance: The potentially improved accuracy in rupture risk stratification of abdominal aortic aneurysms (AAA) by individualized computational simulations is attractive for physicians, scientists, and patients. However, the results of finite element model simulations are highly dependent on the quality and complexity of the underlying finite element models. As a consequence, interpretation of results in many publications is difficult and the results are often not comparable. Unfortunately, most clinically active vascular specialists are not familiar with computational analyses of AAA to evaluate the quality of such studies. For better understanding and to provide insights in computational AAA biomechanics, the effects of more and less sophisticated model assumptions are explained and demonstrated in four exemplary AAA morphologies.

Purpose: Critical leg ischemia (CLI) is associated with a high morbidity and mortality. Therapeutic angiogenesis is still being investigated as a possible alternative treatment option for CLI. CXCL12, a chemokine, is known to have two spliced variants, CXCL12α and CXCL12β, but the significance remains unknown. The study investigated the angiogenic effects of CXCL12, protein expressions of CXCL12, and the receptor CXCR4 in human CLI.Methods: In vitro, human microvascular endothelial cells (HMEC-1) were used. Cell proliferation was assessed using methylene blue assay and cell count method. Apoptosis was determined by counting the pyknotic nuclei after 4′-6-diamidino-2-phenylindole staining and confirmed by caspase-3 assay. We employed matrigel as capillary tube formation assay. The activity of signaling pathways was measured using Western blotting. In vivo, gastrocnemius biopsies were obtained from the lower limbs of patients with CLI and controls (n = 12 each). Immunohistochemistry, double immunofluorescence labeling, and Western blotting were then performed.Results: CXCL12 attenuated HMEC-1 apoptosis (P < .01), stimulated cell proliferation (P < .05) and capillary tube formation (P < .01). Compared with CXCL12α, CXCL12β has a greater effect on apoptosis and cell proliferation (P < .01). Treatment with both variants resulted in time-dependent activation of PI3K/Akt and p44/42 but not p38 MAP kinase. In CLI, CXCL12α was expressed by skeletal muscle fibers with minimal expression of CXCL12β. CXCR4 was extensively expressed and colocalized to microvessels. A significant 2.6-fold increase in CXCL12α and CXCR4 expressions (P < .01) were noted in CLI but not for CXCL12β (P > .05).Conclusions: The study showed that CXCL12β had more potent angiogenic properties but was not elevated in human CLI biopsies. This provided an interesting finding on the role of CXCL12 variants in pathophysiologic angiogenic response in CLI.Clinical Relevance: The in vitro study showed that CXCL12β had more potent angiogenic properties compared to CXCL12α, and both of these act via the p44/42 and PI3K/Akt pathways. The in vivo data using tissues of human CLI confirmed the pathophysiological changes that showed deficient CXCL12β and the increased expression of CXCR4 by microvessels, suggesting that CXCL12 plays an important role in human CLI. Therefore, the use of CXCL12β as a proangiogenic agent may be more likely to provide encouraging results in future experiments and possibly in the use as a possible therapeutic angiogenic agent.

In contrast to internal iliac artery (IIA) occlusion, the use of branch stent-graft (BSG) has been developed as an efficient adjunct in preserving pelvic blood flow. However, the risk of post-procedural type 2 endoleak (EL) remains. We present the case of an 80-year-old man with a juxtarenal aneurysm extending to both common and IIA. The patient was treated with a fenestrated device and a left BSG after embolization of the right IIA branches. At 6 months, the persistence of a type 2 EL associated with aneurysm growth mandated EL embolization through the BSG with a good result. Technical issues are discussed.

Spinal cord ischemia is a rare complication after abdominal aortic surgery and has been attributed to surgical devascularization of the spinal cord, atheroembolization of the cord circulation, or hypoperfusion of cord structures secondary to hypotension or cord edema. We present a diabetic, hypertensive 75-year-old male with endstage renal disease who presented with a 5.5 cm asymptomatic infrarenal abdominal aortic aneurysm, and concomitant 3.5 cm right common iliac artery aneurysm. After undergoing successful endovascular repair with an aorto-uni-iliac device, unilateral hypogastric artery embolization, and femoral-femoral bypass, he was discharged to a rehabilitation facility neurologically intact with a stage 2 decubitus ulcer. He returned on postoperative day 21 with a large stage 4 septic decubitus ulcer, fever, leukocytosis, hypotension, and paraplegia. We hypothesize that the compromised blood flow from the initial reconstruction, combined with the delayed hypotension imposed by sepsis, resulted in spinal cord infarction. He was eventually discharged to a nursing facility with no improvement in his neurologic status. We report the first case of significantly delayed permanent paraplegia after endovascular abdominal aortic aneurysmorrhaphy.

It is a great honor to serve as the 36th President of the New England Society of Vascular Surgery, the oldest regional vascular society in the country. With this honor, of course, come duty and specifically, the assemblage of a Presidential Address. I have reviewed Presidential Addresses delivered before this Society by my teachers and predecessors. The trends seem clear: decide on fact or philosophy, stick to something you are at least vaguely familiar with, avoid boredom, and remember that, in Boston, tradition must be served. The latter facet is a pleasure, as it has been the great honor of my professional life to lead the Vascular Division at the Massachusetts General Hospital founded by Drs Linton and Darling. I hope there will be a certain satisfaction for our membership this morning, because my topic is bound to both the history of our Society and the evolution of vascular surgery over the past 60 or more years.

A 42-year-old female is involved in a motor vehicle accident and presents with a number of injuries. She is hemodynamically stable and is found to have multiple rib fractures, a hemopneumothorax, and several uncomplicated long bone fractures. A CT scan of her chest reveals a traumatic injury to her proximal descending thoracic aorta with evidence of pseudoaneurysm formation and surrounding hematoma (). The following debate attempts to resolve whether open repair remains the gold standard for the treatment of blunt thoracic aortic injuries.

Endovascular management of these life threatening injuries has become the accepted choice of treatment at many trauma centers, but as the authors outline, there remain several unanswered questions.

As the Journal of Vascular Surgery (JVS) initiates a new section on Historical Vignettes, it seems appropriate to revisit how, when, and where the Society for Vascular Surgery (SVS) began and to briefly review what we have accomplished in the more than six decades since. The history of SVS has been written by several authors. These include a book by Harris B. Shumacker, Jr, two Presidential addresses by George Lilly and Jesse Thompson, and, finally, the June 1996 issue of JVS to celebrate the 50th Anniversary of the Society. The current article is a summation of events described in these publications that led to the formation of the Society for Vascular Surgery.

The authors discuss their experience with ruptured juxtarenal aortic aneurysms where the kidneys were subject to cold perfusion during suprarenal aortic cross-clamping. They conclude that this procedure has an associated high mortality and morbidity but cold perfusion may lower the incidence of post-operative acute renal failure.

The authors evaluate their results using autogenous conduit in the reconstruction of portal, splenic, and superior mesenteric vein following resection by the surgical oncologist. They identified reasonable patency and low procedure-related morbidity.

Conclusion: Aspirin and clopidogrel combined are associated with more bleeding than aspirin or clopidogrel alone. Summary: Aspirin is effective as an antithrombotic agent for secondary stroke prevention. It reduces the risk of secondary stroke 15% to 20% compared with placebo (BMJ 1994;308:81-106) but fails to prevent many events; therefore, other antithrombotic agents have been investigated for secondary stroke prevention. All antithrombotic agents, however, carry a bleeding risk, and some bleeding episodes are fatal; for example, bleeding associated with antithrombotic agents for secondary prevention leads to higher mortality in patients with acute coronary syndromes (Circulation 2006;114:774-82). In this report the authors sought to compare bleeding risk associated with secondary stroke prevention regimens for noncardioembolic strokes. They focused on analyzing recent studies of combinations of antiplatelet agents.