Anticoagulation in acute ischemic stroke patients with mechanical heart valves: To bridge or not with heparin. The ESTREM study.

INTRODUCTION: The best therapeutic strategy for patients with mechanical heart valves (MHVs) having acute ischemic stroke during treatment with vitamin K antagonists (VKAs) remain unclear. Being so, we compared the outcomes for: (i) full dose heparin along with VKA (bridging therapy group) and (ii) restarting VKA without heparin (nonbridging group). PATIENTS AND METHODS: For this multicenter observational cohort study, data on consecutive acute ischemic stroke patients with MHV was retrospectively collected from prospective registries. Propensity score matching (PSM) was adopted to adjust for any treatment allocation confounders. The primary outcome was the composite of stroke, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding at 90 days. RESULTS: Overall, 255 out of 603 patients (41.3%) received bridging therapy: 36 (14.1%) had combined outcome, compared with 28 (8.0%) in the nonbridging group (adjusted OR 1.83; 95% CI 1.05-3.18; p = 0.03). Within the bridging group, 13 patients (5.1%) compared to 12 (3.4%) in the nonbridging group had an ischemic outcome (adjusted OR 1.71; 95% CI 0.84-3.47; p = 0.2); major bleedings were recorded in 23 (9.0%) in the bridging group and 16 (4.6%) in the nonbridging group (adjusted OR 1.88; 95% CI 0.95-3.73; p = 0.07). After PSM, 36 (14.2%) of the 254 bridging patients had combined outcome, compared with 23 (9.1%) of 254 patients in the nonbridging group (OR 1.66; 95% CI 0.95-2.85; p = 0.07). CONCLUSION: Acute ischemic stroke patients with MHV undergoing bridging therapy had a marginally higher risk of ischemic or hemorrhagic events, compared to nonbridging patients.

Post-Stroke Detection of Subclinical Paroxysmal Atrial Fibrillation in Patients With Embolic Stroke of Undetermined Source in the Real World Practice: The Empoli ESUS Atrial Fibrillation (E 2 AF) Study.

BACKGROUND: Subclinical paroxysmal atrial fibrillation (AF) is one of the main occult causative mechanisms of embolic stroke of undetermined source (ESUS). Aim of this study was to identify AF predictors, and to develop a score to predict the probability of AF detection in ESUS. METHODS: We retrospectively analyzed ESUS patients undergoing 2-week external electrocardiographic monitoring. Patients with and without AF detection were compared. On the basis of multivariate analysis, predictors of AF were identified and used to develop a predictive score, which was then compared with other existing literature scores. RESULTS: Eighty-two patients, 48 females, mean age±SD 72±10 years, were included. In 36 patients (43.9%) AF was detected. The frequency of age 75 years or above and arterial hypertension, and the median CHA 2 DS 2 -VASc score were significantly higher in patients with AF compared with those without. National Institutes of Health Stroke Scale (NIHSS) score ≥8 was the only independent variable associated with AF detection. We derived the Empoli ESUS-AF (E 2 AF) score (NIHSS ≥8 5 points, arterial hypertension 3 points, age 75 years or above 2 points, age 65 to 74 years 1 point, history of coronary/peripheral artery disease 1 point, left atrial enlargement 1 point, posterior lesion 1 point, cortical or cortical-subcortical lesion 1 point), whose predictive power in detecting AF was good (area under the curve: 0.746, 95% confidence interval: 0.638-0.836) and higher than that of CHA 2 DS 2 -VASc and other scores. CONCLUSIONS: In our study NIHSS score ≥8 was the only independent predictor of post-ESUS-AF detection. The E 2 AF score appears to have a good predictive power for detecting AF. External validations are required.

Predictive Factors for Hemorrhagic Transformation in Acute Ischemic Stroke in the REAL-World Clinical Practice.

BACKGROUND: Few data exists on predictive factors of hemorrhagic transformation (HT) in real-world acute ischemic stroke patients. The aims of this study were: (i) to identify predictive variables of HT (ii) to develop a score for predicting HT. METHODS: We retrospectively analyzed the clinical, radiographic, and laboratory data of patients with acute ischemic stroke consecutively admitted to our Stroke Unit along two years. Patients with HT were compared with those without HT. A multivariate logistic regression analysis was performed to identify independent predictors of HT on CT scan at 24 hours to develop a practical score. RESULTS: The study population consisted of 564 patients with mean age 77.5±11.8 years. Fifty-two patients (9.2%) showed HT on brain CT at 24 hours (4.9% symptomatic). NIHSS score ≥8 at Stroke Unit admission (3 points), cardioembolic etiology (2 points), acute revascularization by systemic thrombolysis and/or mechanical thrombectomy (1 point), history of previous TIA/stroke (1 point), and major vessel occlusion (1 point) were found independent risk factors of HT and were included in the score (Hemorrhagic Transformation Empoli score (HTE)). The predictive power of HTE score was good with an AUC of 0.785 (95% CI: 0.749-0.818). Compared with 5 HT predictive scores proposed in the literature (THRIVE, SPAN-100, MSS, GRASPS, SITS-SIC), the HTE score significantly better predicted HT. CONCLUSIONS: NIHSS score ≥8 at Stroke Unit admission, cardioembolism, urgent revascularization, previous TIA/stroke, and major vessel occlusion were independent predictors of HT. The HTE score has a good predictive power for HT. Prospective studies are warranted.

Thromboembolic Complications in COVID-19 Patients Hospitalized in Italian Ordinary Wards: Data from the Multicenter Observational START-COVID Register.

Background Coronavirus disease 2019 (COVID-19) infection causes acute respiratory insufficiency with severe interstitial pneumonia and extrapulmonary complications; in particular, it may predispose to thromboembolic disease. The reported incidence of thromboembolic complications varies from 5 to 30% of cases. Aim We conducted a multicenter, Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe the clinical characteristics of patients at admission and bleeding and thrombotic events occurring during the hospital stay. Results The number of hospitalized patients included in the START-COVID-19 Register was 1,135, and the number of hospitalized patients in ordinary wards included in the study was 1,091, with 653 (59.9%) being males and 71 years (interquartile range 59-82 years) being the median age. During the observation, two (0.2%) patients had acute coronary syndrome episodes and one patient (0.1%) had an ischemic stroke; no other arterial thrombotic events were recorded. Fifty-nine patients had symptomatic venous thromboembolism (VTE) (5.4%) events, 18 (30.5%) deep vein thrombosis (DVT), 39 (66.1%) pulmonary embolism (PE), and 2 (3.4%) DVT+PE. Among patients with DVT, eight (44.4%) were isolated distal DVT and two cases were jugular thrombosis. Among patients with PE, seven (17.9%) events were limited to subsegmental arteries. No fatal PE was recorded. Major bleeding events occurred in nine (1.2%) patients and clinically relevant nonmajor bleeding events in nine (1.2%) patients. All bleeding events occurred among patients receiving thromboprophylaxis, more frequently when treated with subtherapeutic or therapeutic dosages. Conclusion Our findings confirm that patients admitted to ordinary wards for COVID-19 infection are at high risk for thromboembolic events. VTE recorded among these patients is mainly isolated PE, suggesting a peculiar characteristic of VTE in these patients.

Clinical utility of circulating calprotectin to assist prediction and monitoring of COVID-19 severity: An Italian study.

BACKGROUND: Calprotectin (S100A8/A9) has been identified as a biomarker that can aid in predicting the severity of disease in COVID-19 patients. This study aims to evaluate the correlation between levels of circulating calprotectin (cCP) and the severity of COVID-19. METHODS: Sera from 245 COVID-19 patients and 110 apparently healthy individuals were tested for calprotectin levels using a chemiluminescent immunoassay (Inova Diagnostics). Intensive care unit (ICU) admission and type of respiratory support administered were used as indicators of disease severity, and their correlation with calprotectin levels was assessed. RESULTS: Samples from patients in the ICU had a median calprotectin concentration of 11.6 µg/ml as compared to 3.5 µg/ml from COVID-19 patients who were not in the ICU. The median calprotectin concentration in a cohort of healthy individuals collected before the COVID-19 pandemic was 3.0 µg/ml (95% CI: 2.820-2.969 µg/ml). Patients requiring a Venturi mask, continuous positive airway pressure, or orotracheal intubation all had significantly higher values of calprotectin than controls, with the increase of cCP levels proportional to the increasing need of respiratory support. CONCLUSION: Calprotectin levels in serum correlate well with disease severity and represent a promising serological biomarker for the risk assessment of COVID-19 patients.

Efficacy and Safety of Edoxaban in Cancer-Associated Venous Thromboembolism: A Real World Retrospective Study.

Introduction Few data exist on the use of edoxaban in cancer-associated venous thromboembolism (VTE) outside of clinical trials. Aim of this study was to evaluate the characteristics and outcomes of these patients in a real world clinical setting. Methods We retrospectively analyzed the characteristics of patients with cancer-associated VTE who were prescribed edoxaban. Follow-up at 3, 6, and 12 months was performed: VTE recurrences, bleedings, mortality, cancer progression and treatment, edoxaban interruption and its reason were assessed. Results Fifty-four patients, 38 females (70.4%), mean age 71 ± 14 years, were enrolled. In 38 patients (70.4%), the episode of VTE was the first one, in 28 (51.8%) it was an isolated deep vein thrombosis (DVT), in 13 (24.1%) a pulmonary embolism (PE) associated with DVT, in 13 (24.1%) an isolated PE. Median time between cancer and VTE diagnosis was 6 (interquartile range [IQR] 2-47) months. Median time between VTE diagnosis and edoxaban prescription was 36 (IQR 7-117) days. At 3, 6, and 12 months the incidence of all-cause mortality was 16.6, 22.2, and 38.8%, that of VTE recurrence 1.8, 1.8, and 3.7%, and that of major bleeding 7.4, 9.2, and 12.9%, respectively. No bleeding was fatal. Of the 33 patients alive at 12 months, 32 (96.9%) were still on edoxaban therapy, in seven (21.2%) cancer was in progression. Conclusion Our study, conducted on a real world population of patients with cancer-associated VTE, confirms the results of randomized controlled clinical trials, and supports the use of edoxaban as effective and safe treatment in this context.

Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants: The RENO-EXTEND Study.

BACKGROUND: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. METHODS: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. RESULTS: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA2DS2-VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0-1.3] for each point increase; P=0.05) and hypertension (OR, 2.3 [95% CI, 1.0-5.1]; P=0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0-1.2] for each year increase; P=0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4-14.2]; P=0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4-5.5]; P=0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8-1.7]). CONCLUSIONS: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.

Predictors of poor outcome in tocilizumab treated patients with Sars-CoV-2 related severe respiratory failure: A multicentre real world study.

INTRODUCTION: Despite Tocilizumab is now recognized as a concrete therapeutic option in patients with severe SARS-CoV-2 related respiratory failure, literature lacks about factors influencing the response to it in this context. Therefore, the aim of our study was to provide evidence about predictors of poor outcome in Tocilizumab treated patients in the real-world practice. MATERIALS AND METHODS: We retrospectively analyzed clinical, laboratory and chest computer tomography (CCT) data of patients firstly admitted in non Intensive Care Units (ICU) and suffering from severe respiratory failure, who were treated with the IL-6 antagonist Tocilizumab. We compared patients who died and/or required admission to ICU with oro-tracheal intubation (OTI) with those who did not. RESULTS: Two hundreds and eighty-seven patients (29.9% females) with mean age ± SD 64.1 ± 12.6 years were the study population. In-hospital mortality was 18.8%, while the composite endpoint in-hospital mortality and/or ICU admission with OTI occurred in 23.7%. At univariate analysis, patients who died and/or were admitted to ICU with OTI were significantly older and co-morbid, had significantly higher values of creatinine, C-reactive protein (CRP) and procalcitonin and lower lymphocytes count, PaO2/FiO2 ratio (P/F) and room air pulsossimetry oxygen saturation (RAO2S) at hospital admission. Computed tomography ground glass opacities (CT-GGO) involving the pulmonary surface ≥ 50% were found in 55.4% of patients who died and/or were admitted to ICU with OTI and in 21.5% of patients who did not (p=0.0001). At multivariate analysis, age ≥ 65 years (OR 17.3, 95% CI: 3.7-81.0), procalcitonin ≥ 0.14 (OR 9.9, 95%CI: 1.7-56.1), RAO2S ≤ 90% (OR 4.6, 95%CI: 1.2-17.0) and CCT-GGO involvement ≥ 50% (OR 5.1, 95%CI: 1.2-21.0) were independent risk factors associated with death and/or ICU admission with OTI. CONCLUSION: Tocilizumab has shown to improve outcome in patients with severe respiratory failure associated to SARS-CoV-2 related pneumonia. In our multicentre study focusing on Tocilizumab treated severe COVID-19 patients, age ≥ 65 years, procalcitonin ≥ 0.14 ng/mL, RAO2S ≤ 90% and CCT-GGO involvement ≥ 50% were independent factors associated with poor outcome.

Prognostic role of Interleukin-6/lymphocytes ratio in SARS-CoV2 related pneumonia.

INTRODUCTION AND AIM: Interleukin-6 to lymphocyte (IL-6/Lym) ratio has been identified as a potential prognostic tool in patients with SARS-CoV2 related pneumonia. The aim of our study was to compare the prognostic power of IL-6/Lym ratio with other biomarkers in patients initially admitted in a non intensive unit and suffering for respiratory failure associated with SARS-CoV2 related pneumonia. MATERIALS AND METHODS: IL-6/Lym ratio, IL-6, D-Dimer, D-Dimer/fibrinogen ratio, fibrinogen, C-reactive protein (CRP), lymphocytes count and neutrophil/lymphocyte (N/L) ratio collected at hospital admission were tested as prognosticators of negative outcome, defined as combined endpoint in-hospital mortality and/or Intensive Care Unit (ICU) admission requiring oro-tracheal intubation (OTI). RESULTS: Study population encompassed two hundreds and twenty-three patients (46% females) with mean age ± DS 69.4 ± 13.3 years. Eighty-nine patients (39.9%) suffered for severe respiratory failure and required non invasive ventilation, helmets and/or high flow nasal cannula. Fourty-one patients (18.3%) died during hospital stay and/or required OTI. In these patients mean values of IL-6/Lym ratio, IL-6, CRP and N/L were significantly higher and lymphocytes count was significantly lower compared with patients discharged alive and/or not requiring OTI, while no difference was found in mean values of D-Dimer, D-Dimer/Fibrinogen ratio and fibrinogen. AUC (0.797, 95% CI: 0.738-0.848) of IL-6/Lym ratio was the highest compared with those of all the other analyzed biomarkers and the difference was significant with the exception of IL-6. At multivariate logistic regression IL-6/Lym ratio > 66.5 resulted the only independent biomarker associated with mortality and/or OTI (OR 5.65; 95% 1.63-19.54). CONCLUSION: IL-6/Lym ratio seems to be an optimal prognosticator in SARS-CoV2 related pneumonia. Its routinary use in COVID-19 patients could be warranted.

Prognostic determinants in patients with non traumatic intracerebral hemorrhage: a real life report.

Background and aim: Nontraumatic intracerebral hemorrhage (ICH) remains a devastating disease for high in-hospital and long-term mortality and residual neurological disability. The aim of our study was to analyze the prognostic factors in patients managed for ICH in the real-life clinical practice.Materials and Methods: We retrospectively analyzed clinical and neuro-radiological data of consecutive patients admitted to our Hospital for ICH along 1 year. In-hospital mortality and 90-day modified Rankin scale (mRS) ≥4 were the study outcomes. Moreover, we compared patients admitted in Intensive Care Unit (ICU) with patients admitted in Stroke Unit (SU).Results: Ninety-eight patients with mean age ± SD 78 ± 12 years were enrolled. In-hospital and 90-day mortality were 36.7% and 41.8%, respectively. Patients who died had a significantly higher percentage of ICH volume >30 mL, irregular shape, lobar location, intraventricular hemorrhage (IVH), midline shift, hydrocephalus, hematoma enlargement, Glasgow Coma Scale (GCS) ≤9 at hospital admission, early neurological worsening (ENW), higher Hemphill ICH score, and underwent oro-tracheal intubation more frequently compared with patients who survived. Patients admitted to ICU were younger and significantly more critical compared with those who were admitted to SU. In-hospital mortality in patients admitted to ICU was 52.6% compared with 25% in patients admitted to SU (p < 0.01). Median mRS score at hospital discharge was 4 (IQR 3-5) and at 90 days was 4 (IQR 3-4). ENW, hematoma enlargement, Hemphill ICH score ≥3 and midline shift >10 mm were found independent risk factors for in-hospital mortality, while age was found as independent risk factor for 90-day mRS ≥4).Conclusion: In real life, prognosis of ICH is associated with clinical and radiological determinants. In our study ENW, hematoma enlargement, Hemphill ICH score ≥3 and midline shift >10 mm were associated with short-term mortality risk, while age with 90-day mRS ≥4.

Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes.

INTRODUCTION: The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. MATERIALS AND METHODS: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. RESULTS: A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). DISCUSSION: our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. CONCLUSIONS: Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.

Age-related burden and characteristics of embolic stroke of undetermined source in the real world clinical practice.

Few data are available on age-related burden and characteristics of embolic stroke of undetermined source (ESUS) in the real world clinical practice. The aim of our study was to provide information about it. We retrospectively analyzed data of patients consecutively admitted to our Stroke Unit along 1 year (2017, November 1st-2018, October 31st). The etiology of ischemic stroke was defined at hospital discharge; ESUS was considered as a subset of cryptogenic stroke, and defined according to the 2014 international criteria. In the analyzed period, 306 patients, 52.3% females, mean age ± SD 77.9 ± 11.9 years, were discharged with diagnosis of ischemic stroke. Ischemic strokes of cardioembolic and lacunar origin were the most frequent subtypes: 30.1% and 29.4%, respectively. Cardioembolic strokes were particularly frequent in patients ≥ 75 years, and almost always associated with atrial fibrillation. Overall, in 80 patients (26.1%) the etiology of stroke was undetermined; in 25 (8.2%) it remained undefined because of death or severe comorbidity, making further diagnostic work-up not worthy. Cryptogenic stroke occurred in 55 patients (18%), and ESUS criteria were satisfied in 39 of them (12.7%). According to age, cryptogenic stroke was diagnosed in 21.1% (21.1% ESUS) of patients < 65 years, 24.2% (19.4% ESUS) of patients aged 65-74 years, 15.5% (9.2% ESUS) of patients ≥ 75 years. After diagnostic work-up, patent foramen ovale was most commonly associated with ESUS (17.9%), especially in patients < 65 years (62.5%); covert paroxysmal atrial fibrillation was detected in 10.5% of ESUS patients ≥ 75 years. In the real world clinical practice, the frequency of ischemic strokes of undetermined etiology, and of those satisfying ESUS criteria, is not negligible, especially in younger patients. A thorough diagnostic work-up, with an age-specific approach, is therefore necessary and of the utmost importance for the identification of stroke etiology, in order to optimize secondary stroke prevention strategies.

Management of oral anticoagulation in very old patients with non valvular atrial fibrillation related acute ischemic stroke.

The optimal management of oral anticoagulation (OAC) in the acute phase of non valvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS) remains controversial, especially in very old patients. Therefore, the aim of our study was to evaluate the practical management of OAC in this context. We conducted an observational retrospective study on patients 85-years old and older admitted to two Italian hospitals for NVAF-related AIS. For each patient, clinical and brain computed tomography data were recorded. Type of OAC (vitamin K antagonists, VKAs or Direct Oral Anticoagulants, DOACs), dosage and starting day after AIS were registered. For each patient 90-day all cause mortality, stroke recurrence, any bleeding and modified Rankin scale (mRS) were reported. One-hundred-seventeen patients, with mean age 89.2 ± 3.4 years, were enrolled. In-hospital and 90-day mortality (out of 109 patients) were 6% and 19.7%, respectively. OAC was started in 93 patients (80.5%), on average after 6 ± 3 days from the acute event. Of them, 88 patients (94.6%) received DOACs, while 5 (5.4%) received VKAs. Patients receiving OAC were significantly younger and suffering from less severe stroke compared with patients who did not receive OAC. Patients receiving OAC presented a reduced in-hospital (2.2% vs. 20.8%, p < 0.004) and 90-day all-cause mortality (9.4% vs. 62.5%, p < 0.001). In patients receiving DOACs, low dosages were used in 87.5% of patients. The use of OAC was not associated with an increased rate of hemorrhagic transformation (HT) during hospitalization (13.2% vs. 9.5%, p = 0.54) or any bleeding at 90-day follow-up. Severe dysphagia and mRS ≥ 4 were found to be independent risk factors for not prescribing OAC. The optimal management of OAC in very old patients suffering from NVAF-related AIS remains a dilemma. In our real world study the majority of patients received OAC as secondary prevention treatment without increase in bleeding risk. Dysphagia and severe disability were independent factors for not prescribing OAC. Further investigations aimed at identifying the optimal approach to OAC during the acute phase of NVAF-related ischemic stroke in this subgroup of patients are warranted.

Direct Oral Anticoagulants in Patients Undergoing Urgent Reperfusion for Nonvalvular Atrial Fibrillation-Related Ischemic Stroke: A Brief Report on Literature Evidence.

INTRODUCTION: The optimal timing for starting anticoagulation in the early phase of nonvalvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS) remains a challenge, especially in patients undergoing urgent reperfusion by systemic thrombolysis or mechanical thrombectomy. The aim of our study was to review the literature evidence reporting on safety of direct oral anticoagulants (DOACs) starting in the early phase of NVAF-related AIS undergoing systemic thrombolysis and/or mechanical thrombectomy. MATERIALS AND METHODS: We reviewed the PubMed databases searching articles reporting on efficacy and safety of DOACs starting time within two weeks from AIS onset in patients undergoing systemic thrombolysis and/or mechanical thrombectomy. RESULTS: Three studies were selected, overall including one hundred and six patients (62 females, 58.4%). Median National Institute of Health Stroke Scale (NIHSS) score at hospital admission ranged from 9 to 13 points. Median DOACs starting time ranged from 2 to 6 days. Median CHA2DS2-VASC score ranged from 4 to 6 points. Follow-up was limited to 14 days in one study, 30 days in another, and 90 days in a third one. Overall, stroke recurrence and/or intracranial bleeding occurred in two patients (1.9%) and no patient died at follow-up. CONCLUSION: Small sample size real life studies seem to demonstrate that the introduction of DOACs in the early phase of NVAF-related AIS undergoing urgent reperfusion is efficacious and safe. Prospective RCTs are necessary to confirm these findings.