Apixaban Versus Vitamin K Antagonists in Patients With Antiphospholipid Syndrome: A Cohort Study.

ABSTRACT: Current guidelines recommend that direct anticoagulants should not be used in prevention of recurrent thrombosis in patients with antiphospholipid syndrome (APS). However, except for triple-positive APS and rivaroxaban use, little evidence supports such recommendation. In a real-life cohort study, we evaluated the risk of thromboembolism and bleeding in patients with APS on apixaban versus vitamin K antagonists (VKA). We enrolled 152 patients with APS (aged 44 years [interquartile range 36-56], 83% women), including 66 patients treated with apixaban 5 mg bid and 86 with warfarin (target international normalized ratio [INR] 2-3). During a median follow-up of 53 months, we recorded venous thromboembolism, ischemic stroke, or myocardial infarction, along with major bleeding. We observed 4 thrombotic events (6.1%, 3 venous thromboembolism and 1 ischemic stroke) in patients on apixaban and 12 events (14%, 9 venous thromboembolism, 2 ischemic strokes and 1 myocardial infarction) in VKA patients. Patients with APS on apixaban had similar risk of recurrent thromboembolism compared with those on warfarin (hazard ratio [HR] = 0.327, 95% confidence interval [CI]: 0.104-1.035). Thromboembolic events occurred less commonly in statin users (8% vs. 50%, P = 0.01) and more frequently in triple-positive APS (50% vs. 22.1%, P = 0.028) and in patients with higher D-dimer at baseline ( P = 0.023); the latter difference was present in the apixaban group ( P = 0.02). Patients on apixaban had similar risk of major bleeding compared with warfarin (HR = 0.54, 95% CI: 0.201-1.448). In real-life patients with APS, apixaban appears to be similar to VKA for the prevention of thromboembolism and risk of bleeding, which might suggest that some patients with APS could be treated with apixaban.

Diabetes Mellitus and Clinical Outcomes in Carotid Artery Revascularization Using Second-Generation, MicroNet-Covered Stents: Analysis from the PARADIGM Study.

Introduction: Carotid artery stenting (CAS) using conventional (single-layer) stents is associated with worse clinical outcomes in diabetes mellitus (DM) vs. non-DM patients: an effect driven largely by lesion-related adverse events. CAS outcomes with MicroNet-covered stents (MCS) in diabetic patients have not been evaluated. Aim: To compare short- and long-term clinical outcomes and restenosis rate in DM vs. non-DM patients with carotid stenosis treated using MCS. Materials and Methods: In a prospective study in all-comer symptomatic and increased-stroke-risk asymptomatic carotid stenosis, 101 consecutive patients (age 51-86 years, 41% diabetics) underwent 106 MCS-CAS. Clinical outcomes and duplex ultrasound velocities were assessed periprocedurally and at 30 days/12 months. Results: Baseline characteristics of DM vs. non-DM patients were similar except for a higher prevalence of recent cerebral symptoms in DM. Type 1 and type 1+2 plaques were more prevalent in DM patients (26.7% vs. 9.8%, p = 0.02; 62.2% vs. 37.7%, p = 0.01). Proximal embolic protection was more prevalent in DM (60% vs. 36%; p = 0.015). 30-day clinical complications were limited to a single periprocedural minor stroke in DM (2.4% vs. 0%, p = 0.22). 12-month in-stent velocities and clinical outcomes were not different (death rate 4.8% vs. 3.3%; p = 0.69; no new strokes). Restenosis rate was not different (0% vs. 1.7%, p = 0.22). Conclusions: MCS may offset the adverse impact of DM on periprocedural, 30-day, and 12-month clinical complications of CAS and minimize the risk of in-stent restenosis. In this increased-stroke-risk cohort, adverse event rate was low both in DM and non-DM. Further larger-scale clinical datasets including extended follow-ups are warranted.

Eligible-and-enrolled vs. eligible-but-not-enrolled patients with chronic ischaemic heart failure in randomized clinical trials of myocardial regeneration.

Introduction: Clinical trial applicability to routine clinical practice is a fundamental consideration. Little is known about factors that determine enrolment (vs. non-enrolment) in chronic ischaemic heart failure (CIHF) interventional randomized controlled trials (iRCT). Aim: To compare clinical characteristics and medical therapy in eligible-and-enrolled (E-E) vs. eligible-but-not-enrolled (E-NE) patients in CIHF myocardial regeneration iRCTs. Material and methods: Clinical characteristics and medical treatment were compared for E-E and E-NE in 4 periods (32 months): P1 (iRCT#1 recruitment), P2 (between iRCT#1 and iRCT#2), P3 (iRCT#2 recruitment), P4 (post iRCT#2). iRCT#1 and iRCT#2 shared inclusion/exclusion criteria. Results: Evaluation involved 5,436 hospitalized patients (P1-P4; CIHF-526). 283 were iRCT eligible (53.8%). The eligibility rate was similar throughout P1-P4 (43.1-58.5%, p = 0.08). Eligible patient characteristics and pharmacotherapy did not differ in recruitment vs. non-recruitment periods. Principal reasons for ineligibility were recent/planned cardiac intervention outside iRCT (22.8%), age above threshold (14.6%) and coexisting disease as the exclusion criterion (12.2%). Primary reasons for eligible patient non-enrolment (n = 89) were other trial participation (52.8%) and no consent (28.1%). E-E patients did not differ from E-NE in characteristics including CIHF medical management and clinical stage; the exception was more severe left ventricular impairment in E-E (LVEF 31.2 vs. 33.9%, p = 0.039; end-diastolic volume 197.8 vs. 160.4 ml, p < 0.0001). Conclusions: CIHF medical management was similar in E-E and E-NE. Ineligibility resulted mainly from recent/planned intervention outside iRCT and age > 80 years. LV impairment was more severe in E-E patients, consistent with higher-risk patient enrolment in CIHF-iRCTs. This contrasts with typical lower-risk patient enrolment in other cardiovascular RCT types and populations.

Virtual Histology to Evaluate Mechanisms of Pulmonary Artery Lumen Enlargement in Response to Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) results from an obstruction of pulmonary arteries (PAs) by organized thrombi. The stenosed PAs are targeted during balloon pulmonary angioplasty (BPA). We aimed to evaluate the mechanism of BPA in inoperable patients with CTEPH. We analyzed stenosed PAs with intravascular grey-scale ultrasound (IVUS) to determine the cross-sectional area (CSA) of arterial lumen and of organized thrombi. The composition of organized thrombi was assessed using virtual histology. We distinguished two mechanisms of BPA: Type A with dominant vessel stretching, and type B with dominant thrombus compression. PAs were assessed before (n = 159) and after (n = 98) BPA in 20 consecutive patients. Organized thrombi were composed of dark-green (57.1 (48.0-64.0)%), light-green (34.0 (21.4-46.4)%), red (6.4 (2.9-11.7)%;) and white (0.2 (0.0-0.9)%) components. The mechanism type depended on vessel diameter (OR = 1.09(1.01-1.17); p = 0.03). In type B mechanism, decrease in the amount of light-green component positively correlated with an increase in lumen area after BPA (r = 0.50; p = 0.001). The mechanism of BPA depends on the diameter of the vessel. Dilation of more proximal PAs depends mainly on stretching of the vessel wall while dilation of smaller PAs depends on compression of the organized thrombi. The composition of the organized thrombi contributes to the effect of BPA.