Statistical reanalysis of vascular event outcomes in primary and secondary vascular prevention trials

Background Vascular prevention trials typically use dichotomous event outcomes although this may be inefficient statistically and gives no indication of event severity. We assessed whether ordinal outcomes would be more efficient and how to best analyse them. Methods Chief investigators of vascular prevention randomised controlled trials that showed evidence of either benefit or harm, or were included in a systematic review that overall showed benefit or harm, shared individual participant data from their trials. Ordered categorical versions of vascular event outcomes (such as stroke and myocardial infarction) were analysed using 15 statistical techniques and their results then ranked, with the result with the smallest p-value given the smallest rank. Friedman and Duncan’s multiple range tests were performed to assess differences between tests by comparing the average ranks for each statistical test. Results Data from 35 trials (254,223 participants) were shared with the collaboration. 13 trials had more than two treatment arms, resulting in 59 comparisons. Analysis approaches (Mann Whitney U, ordinal logistic regression, multiple regression, bootstrapping) that used ordinal outcome data had a smaller average rank and therefore appeared to be more efficient statistically than those that analysed the original binary outcomes. Conclusions Ordinal vascular outcome measures appear to be more efficient statistically than binary outcomes and provide information on the severity of event. We suggest a potential role for using ordinal outcomes in vascular prevention trials.

PAI-1 in Diabetes: Pathophysiology and Role as a Therapeutic Target

Hypofibrinolysis is a key abnormality in diabetes and contributes to the adverse vascular outcome in this population. Plasminogen activator inhibitor (PAI)-1 is an important regulator of the fibrinolytic process and levels of this antifibrinolytic protein are elevated in diabetes and insulin resistant states. This review describes both the physiological and pathological role of PAI-1 in health and disease, focusing on the mechanism of action as well as protein abnormalities in vascular disease with special focus on diabetes. Attempts at inhibiting protein function, using different techniques, are also discussed including direct and indirect interference with production as well as inhibition of protein function. Developing PAI-1 inhibitors represents an alternative approach to managing hypofibrinolysis by targeting the pathological abnormality rather than current practice that relies on profound inhibition of the cellular and/or acellular arms of coagulation, and which can be associated with increased bleeding events. The review offers up-to-date knowledge on the mechanisms of action of PAI-1 together with the role of altering protein function to improve hypofirbinolysis. Developing PAI-1 inhibitors may form for the basis of future new class of antithrombotic agents that reduce vascular complications in diabetes.

Long Term Vascular Outcomes in Patients with Mixed Location Intracerebral Hemorrhage and Microbleeds

ObjectiveTo determine whether mixed location intracerebral hemorrhages/microbleeds (Mixed-ICH) is a risk factor for vascular unfavorable outcome compared to cerebral amyloid angiopathy-related ICH (CAA-ICH) or strictly deep hypertensive intracerebral hemorrhage/microbleeds (HTN-ICH).Methods300 patients with spontaneous ICH were included. Clinical data, neuroimaging markers and follow-up outcomes (recurrent ICH, ischemic stroke and vascular death) were compared between Mixed-ICH (n=148), CAA-ICH (n=32) and HTN-ICH (n=120). The association between follow-up events and neuroimaging markers were explored using multivariable Cox regression models.ResultsPatients with Mixed-ICH are older (65.6±12.1 years vs 58.1±13.3 years, p<0.001) than HTN-ICH, but younger than CAA-ICH (73.3±13.8 years, p=0.001). Compared to CAA-ICH, Mixed-ICH has similar incidence of vascular event (all p>0.05). Compared to HTN-ICH, Mixed-ICH is associated with higher ICH recurrence (hazard ratio [HR]=3.0, 95% confidence interval [CI]: 1.2-7.7), more ischemic stroke (HR=8.2, 95% CI: 1.0-65.8), and vascular composite outcome (HR=3.5, 95% CI: 1.5-8.2) after adjustment for age and sex. In patients with Mixed-ICH, the presence of cortical superficial siderosis (cSS) is associated the development of ICH recurrence (HR=4.8, 95% CI 1.0-23.2), ischemic stroke (HR=8.8, 95% CI: 1.7-45.5), and vascular composite outcome (HR=6.2, 95% CI: 1.9-20.2). The association between cSS and ischemic stroke (p=0.01) or vascular composite outcome (p=0.003) remained significant after further adjustment for other radiological markers.ConclusionsMixed-ICH harbors higher risk of unfavorable vascular outcome than HTN-ICH. Presence of cSS in Mixed-ICH independently predicts vascular event, suggesting the contribution of detrimental effect due to coexisting CAA.

Abstract WMP107: Outcomes in Mixed Location Intracerebral Hemorrhage and Microbleeds

Objective: Patients with mixed location intracerebral hemorrhages/microbleeds (Mixed-ICH) have predominantly hypertensive vasculopathy rather than cerebral amyloid angiopathy (CAA), but the long-term outcomes in Mixed-ICH is unknown. In this study, we aimed to determine whether Mixed-ICH is a risk factor for vascular unfavorable outcome compared to CAA-ICH or strictly deep hypertensive intracerebral hemorrhage/microbleeds (HTN-ICH). Methods: 305 consecutive ICH patients were included. Clinical data, neuroimaging markers and follow-up outcomes (recurrent ICH, ischemic stroke and vascular death) were compared between Mixed-ICH (n=151), CAA-ICH (n=33) and HTN-ICH (n=121). The association between follow-up events and neuroimaging markers were explored using multivariable Cox regression models. Results: Mixed-ICH patients were older (65.9±12.4 vs 58.1±13.2, p<0.001) than HTN-ICH, but younger than CAA-ICH patients (73.8 ± 13.9, p=0.001). The survival curves of follow-up outcomes were shown in the Figure. Compared to CAA-ICH, Mixed-ICH has similar incidence of vascular event (all P>0.05). Compared to HTN-ICH, Mixed-ICH is associated with higher ICH recurrence (hazard ratio [HR]=3.0 [1.2-7.7], p=0.021), more ischemic stroke (HR=8.2 [1.0-65.8], p=0.048), and vascular composite outcome (HR=3.5 [1.5-8.2], p=0.003) after adjustment for age and sex. In patients of Mixed-ICH, the presence of cortical superficial siderosis (cSS) is associated the development of ICH recurrence (p=0.048), ischemic stroke (p=0.009), and vascular composite outcome (p=0.008). The association between cSS and vascular composite outcome remains significant after further adjustment for microbleed number, lacune and WMH volume (p=0.019). Conclusions: Mixed-ICH harbors higher risk of unfavorable vascular outcome than HTN-ICH. Presence of cSS in Mixed-ICH independently predicts vascular event, suggesting the contribution of detrimental effect due to coexisting CAA.

Options to achieve proximal sealing zone during endovascular repair of abdominal aortic aneurysm and correlated classification

Since its first development, endovascular aortic aneurysmal repair (EVAR) has largely evolved, and several types of endografts are currently available including bifurcated grafts with supra or infra-renal fixation, fenestrated (FEVAR). Technical advances have led to propose EVAR in patients with challenging anatomy and the indications for using endografts mainly depend on patients’ vascular anatomical characteristics and on the instructions for use. Even if the minimal requirements for standard commercially available endografts have been defined, there is a lack of consensus to help surgeons to choose the most appropriate approach. Here, we propose a four-class abdominal aortic aneurysm (AAA) categorization based on the morphology and the length of the necks considered as landing zones as well as markers of potential evolution of the AAA. This pragmatic classification may help to clarify the decision-making process for selecting the most appropriate endovascular device to treat AAA in accordance with the anatomy and the foreseeable evolution and delayed complication risk to anticipate vascular outcome.

A 7-Year Single-Center Experience of Transfemoral TAVI: Evolution of Surgical Activity and Impact on Vascular Outcome

Transcatheter aortic valve implantation (TAVI) has become a well-established alternative to open surgery to treat aortic stenosis. We describe our 7-year TAVI experience using transfemoral access and identity changes in surgical activity and evaluate its impact on postoperative vascular outcomes. Consecutive patients (N = 340) who underwent TAVI with percutaneous transfemoral access were retrospectively included and divided into 4 quartiles according to the date of intervention. Vascular outcomes were classified according to the Valve Academic Research Consortium 2 classification. The number of patients who underwent transfemoral TAVI increased over time and their clinical characteristics evolved, with a lower Society of Thoracic Surgeons score and less comorbidities. The material used evolved and TAVI could be performed despite higher iliac calcification and tortuosity scores. With experience, the procedural time, the postoperative length of stay at hospital, and the 30-day postoperative mortality significantly decreased. No significant change was observed for vascular outcome, except for minor hematoma. We witnessed an increase in transfemoral TAVI procedure, with changes in clinical and procedural characteristics associated with an improvement in postoperative outcomes.