White, Christopher J.

Introduction: The relative performance of carotid artery stenting (CAS) and carotid endarterectomy (CEA) among Medicare beneficiaries in routine clinical practice has not been established. Objective: To compare the performance of CAS relative to CEA among Medicare beneficiaries. Methods: We linked Medicare data (2000-2009) to the Society for Vascular Surgery’s Vascular Registry (SVS-VR; 2005-2008) and to the NCDR® Carotid Artery Revascularization and Endarterectomy Registry (CARE; 2006-2008/9). Medicare patients aged ≥66 years undergoing CAS or CEA were followed from the procedure date for the outcomes of death, stroke/transient ischemic attack (TIA), peri-procedural myocardial infarction (MI) or a composite endpoint for these outcomes. We derived high-dimensional propensity scores using registry and Medicare data to control for patient-level factors and adjusted for provider-level factors including past-year CAS/CEA physician and hospital volume, hospital ownership, teaching affiliation, and hospital size in a Cox regression model comparing CAS to CEA. Results: Among 5,254 SVS-VR (1,999 CAS and 3,255 CEA) and 4,055 CARE (2,824 CAS and 1,231 CEA) patients, CAS patients were more often at higher surgical risk (SVS-VR: 96.7% vs. 44.5%; CARE: 71.3% vs. 44.7%) and had a higher comorbidity burden. Crude outcome risks for death and stroke/TIA were lower for CEA. Adjusting for patient-level factors drove estimates downwards for CAS relative to CEA but only after further adjustment for provider-level factors did the performance of CAS and CEA become comparable on all outcomes (figure 1). Conclusion: Performance of CAS and CEA among Medicare beneficiaries was comparable after accounting for patient- and provider-level factors, which is consistent with landmark trials. Further studies are needed to understand the role of heterogeneity in provider-level characteristics.

Introduction: Outcomes from endovascular procedures are highly dependent on the experience and skill of the operating physician. The multi-disciplinary CREST-2 Interventional Management Committee (IMC) was charged with credentialing a cohort of skilled interventionists with adequate contemporary case volumes. Methods: Applicants were required to submit 25 consecutive cases completed within 5 years as primary operator out of a required total experience of ≥ 50 cases (≥ 20 for operators completing training). Interventionists not approved on initial review were asked to submit additional cases (with procedural angiograms), the number depending on quality and recent-quantity of the cases. Results: The IMC has had 102 meetings, and 283 interventionists have been evaluated: 104 (37%) interventionists were cardiologists, 64 (23%) vascular surgeons, 42 (15%) neurosurgeons, 32 (11%) neuroradiologists, 26 (9%) neurologists, 9 (3%) interventional radiologists, and 6 (2%) other. The mean total experience among the 226 interventionists with available information was 220±263 carotid stent cases (median 135; range 10-2500). A total of 7037 cases have been reviewed by the IMC, dating from August 2001 to April 2016, with 3366 symptomatic, 3541 asymptomatic and 130 undetermined. The range of cases reviewed per interventionist was 5 to 50. Of the 251 interventionists with sufficient periprocedural follow-up data, no stroke events were reported by 152 (60.5%), and at least one or more stroke events were reported by 99 (39.5%). The IMC has approved 115 interventionists, 29 at the first review and 86 subsequently, based upon submission and review of 631 additional contemporary cases (mean=7 cases per interventionist); 122 have approval pending submission of additional cases; 33 have been denied; 8 have been deferred; 4 have been approved for the CREST-2 Companion Registry only; and 1 is pending decision. Discussion: Rigorous evaluation and credentialing of carotid stenters in CREST-2 has been demanding, for the candidates and for the evaluators. Yet the cohort of interventionists so selected should be able to provide the high-quality stenting outcomes necessary for acceptance of the trial results.

Background: Paclitaxel-containing devices (PTXDs) significantly reduce reintervention in patients with symptomatic femoropopliteal peripheral artery disease. A recent aggregate-data meta-analysis reported increased late mortality in patients with peripheral artery disease treated with PTXDs. We performed an individual patient data meta-analysis to evaluate mortality. Methods: Manufacturers of US Food and Drug Administration–approved and commercially available devices in the United States provided deidentified individual patient data for independent analysis. Cox proportional hazards 1-stage meta-analysis models using intention-to-treat methods were used for the primary analysis. A secondary analysis of recovered missing vital status data was performed. The impact of control crossover to PTXDs, cause-specific mortality, and drug dose mortality were assessed. Results: A total of 2185 subjects and 386 deaths from 8 PTXD trials with 4-year median follow-up were identified. The primary analysis indicated a 38% (95% CI, 6% to 80%) increased relative mortality risk, corresponding to 4.6% absolute increase, at 5 years associated with PTXD use. Control and treatment arm loss to follow-up and withdrawal were 24% and 23%, respectively. With inclusion of recovered vital status data, the excess relative mortality risk was 27% (95% CI, 3%–58%). This observation was consistent across various scenarios, including as-treated analyses, with no evidence of increased risk over time with PTXDs. Mortality risk tended to be increased for all major causes of death. There were no subgroup differences. No drug dose–mortality association was identified. Conclusions: This individual patient data meta-analysis, based on the most complete available data set of mortality events from PTXD randomized controlled trials, identified an absolute 4.6% increased mortality risk associated with PTXD use.

An increasing number of patients have refractory angina despite optimal medical therapy and are without further revascularization options. Preclinical studies indicate that human CD34 + stem cells can stimulate new blood vessel formation in ischemic myocardium, improving perfusion and function. In ACT34-CMI ( N = 167), patients treated with autologous CD34 + stem cells had improvements in angina and exercise time at 6 and 12 months compared to placebo; however, the longer-term effects of this treatment are unknown. ACT34 was a phase II randomized, double-blind, placebo-controlled clinical trial comparing placebo, low dose (1 × 10 5 CD34/kg body weight), and high dose (5 × 10 5 CD34/kg) using intramyocardial delivery into the ischemic zone following NOGA ® mapping. To obtain longer-term safety and efficacy in these patients, we compiled data of major adverse cardiac events (MACE; death, myocardial infarction, acute coronary syndrome, or heart failure hospitalization) up to 24 months as well as angina and quality of life assessments in patients who consented for 24-month follow-up. A total of 167 patients with class III–IV refractory angina were randomized and completed the injection procedure. The low-dose-treated patients had a significant reduction in angina frequency ( p = 0.02, 0.035) and improvements in exercise tolerance testing (ETT) time ( p = 0.014, 0.017) compared to the placebo group at 6 and 12 months. At 24 months, patients treated with both low-and high-dose CD34 + cells had significant reduction in angina frequency ( p = 0.03). At 24 months, there were a total of seven deaths (12.5%) in the control group versus one (1.8%) in the low-dose and two (3.6%) in the high-dose ( p = 0.08) groups. At 2 years, MACE occurred at a rate of 33.9%, 21.8%, and 16.2% in control, low-, and high-dose patients, respectively ( p = 0.08). Autologous CD34 + cell therapy was associated with persistent improvement in angina at 2 years and a trend for reduction in mortality in no-option patients with refractory angina.

Background— Fibromuscular dysplasia (FMD), a noninflammatory disease of medium-size arteries, may lead to stenosis, occlusion, dissection, and/or aneurysm. There has been little progress in understanding the epidemiology, pathogenesis, and outcomes since its first description in 1938. Methods and Results— Clinical features, presenting symptoms, and vascular events are reviewed for the first 447 patients enrolled in a national FMD registry from 9 US sites. Vascular beds were imaged selectively based on clinical presentation and local practice. The majority of patients were female (91%) with a mean age at diagnosis of 51.9 (SD 13.4 years; range, 5–83 years). Hypertension, headache, and pulsatile tinnitus were the most common presenting symptoms of the disease. Self-reported family history of stroke (53.5%), aneurysm (23.5%), and sudden death (19.8%) were common, but FMD in first- or second-degree relatives was reported only in 7.3%. FMD was identified in the renal artery in 294 patients, extracranial carotid arteries in 251 patients, and vertebral arteries in 82 patients. A past or presenting history of vascular events were common: 19.2% of patients had a transient ischemic attack or stroke, 19.7% had experienced arterial dissection(s), and 17% of patients had an aneurysm(s). The most frequent indications for therapy were hypertension, aneurysm, and dissection. Conclusions— In this registry, FMD occurred primarily in middle-aged women, although it presents across the lifespan. Cerebrovascular FMD occurred as frequently as renal FMD. Although a significant proportion of FMD patients may present with a serious vascular event, many present with nonspecific symptoms and a subsequent delay in diagnosis.