Associations between insulin resistance and thrombotic risk factors in high-risk South Asian subjects

2003 ◽  
Vol 20 (8) ◽  
pp. 651-655 ◽  
Author(s):  
K. Kain ◽  
A. J. Catto ◽  
P. J. Grant
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
High Risk ◽  
South Asian ◽  
Thrombotic Risk

scholarly journals Insulin Resistance and Atherosclerosis: Implications for Insulin-Sensitizing Agents

2019 ◽  
Vol 40 (6) ◽  
pp. 1447-1467 ◽  
Author(s):  
Antonino Di Pino ◽  
Ralph A DeFronzo
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Insulin Resistance ◽  
High Risk ◽  
Cardiometabolic Risk ◽  
Considerable Evidence ◽  
Risk Patients ◽  
Cv Disease ◽  
The Impact

Abstract Patients with type 2 diabetes mellitus (T2DM) are at high risk for macrovascular complications, which represent the major cause of mortality. Despite effective treatment of established cardiovascular (CV) risk factors (dyslipidemia, hypertension, procoagulant state), there remains a significant amount of unexplained CV risk. Insulin resistance is associated with a cluster of cardiometabolic risk factors known collectively as the insulin resistance (metabolic) syndrome (IRS). Considerable evidence, reviewed herein, suggests that insulin resistance and the IRS contribute to this unexplained CV risk in patients with T2DM. Accordingly, CV outcome trials with pioglitazone have demonstrated that this insulin-sensitizing thiazolidinedione reduces CV events in high-risk patients with T2DM. In this review the roles of insulin resistance and the IRS in the development of atherosclerotic CV disease and the impact of the insulin-sensitizing agents and of other antihyperglycemic medications on CV outcomes are discussed.

Essential Thrombocythaemia in Young Adults: Clinical Characteristics and Outcomes – a Single Center Experience

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5060-5060
Author(s):  
Grace Kam ◽  
Richard Yiu ◽  
Ai Leen Ang ◽  
Yvonne SM Loh ◽  
Yeh Ching Linn ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Disease Progression ◽  
Young Patients ◽  
Medical Attention ◽  
Thrombotic Risk ◽  
Risk Of Death ◽  
Increased Risk ◽  
Thrombosis Rate

Abstract Abstract 5060 Less than 20% of patients with essential thrombocythemia (ET) are diagnosed below the age of 60. Patients with ET have increased risk of thrombosis and bleeding and potential for progression to myelofibrosis (MF) or acute myeloid leukaemia (AML). In limited studies of young patients, the clinical course has been relatively benign with low rates of transformation to AML or MF. Thrombohemorrhagic events are generally few, but higher than that of the general population. This study aims to characterize of a group ET patients diagnosed at age ≤40, their thrombotic and hemorrhagic events, disease progression and treatment given. Patients were identified through a single institution MPN registry. This is an IRB approved registry that captures comprehensive information about patients with ET. Data on patient demographics, treatment, and disease-related events were obtained. Patients were diagnosed from 1975–2011, using either WHO or PVSG criteria depending on date of diagnosis. Kaplan-Meier method was used for survival analysis. 59 patients were diagnosed with ET at age ≤40. Median age of diagnosis was 31. 5years (range 16–40), with a median follow up of 7. 7years (0. 4–33. 8). All were of Asian descent: 81. 4% Chinese, 11. 9% Malay, 3. 4% Indian and 3. 4% Filipino. 40. 7% were male. JAK2 V617F mutation was screened for in 61%. Of these patients, 11 were positive, 25 negative for the mutation. Mean presenting counts were: WBC 10. 7 × 109/L (5. 9–21. 3), Hb 13. 6g/dL (9. 7–16. 4), platelets 957 × 109/L (449–2377). Splenomegaly was noted in 3 patients. 20. 3% had underlying hypertension, 16. 9% hyperlipidemia and 5. 1% diabetes mellitus. One patient had a prior stroke. Another had prior portal vein thrombosis. At diagnosis, 23. 7% were symptomatic, with microvascular symptoms of headache (11. 9%) and giddiness (6. 8%) being most common. The remainder were diagnosed incidentally, on health screening or when seeking medical attention for unrelated conditions. One patient presented with a myocardial infarction at diagnosis, while another had a significant bleeding post hemorrhoidectomy with drop in Hb by >2g/dL (platelet 2457 × 109/L). Based on a history of prior thrombosis, 3 patients were defined as high risk for thrombotic events. 67. 8% of patients had cytoreduction, indications being platelets ≥1500 × 109/L (n=16), presence of risk factors for atherosclerotic disease (n=11) and history/onset of thrombosis (n=5). In 8, the reason for cytoreduction could not be ascertained. Hydroxyurea was most commonly used (62. 7%), followed by anagrelide in 52. 5% and interferon 25. 4%. 5. 1% received busulphan, and 1. 7% 32P. Use of antiplatelet therapy was noted in 83. 8%, most frequently aspirin (76. 5%) and ticlopidine (11. 9%). On follow up, 2 arterial thromboses occurred (stroke, TIA), giving a thrombosis rate of 0. 39%/patients/year. Neither was a recurrent thrombosis. No venous thrombosis or major bleeds occurred. 20. 4% had minor mucocutaneous bleeding; 5 had platelets ≥1500 × 109/L at that time. 3. 4% had disease progression due to MF and another 3. 4% had AML. 3. 4% of patients died due to AML. Median survival was 33. 8years (95% confidence interval 30. 3–35. 5). Initial blood counts, presence of JAK2 and high risk disease status did not correlate with thrombotic risk, risk of death or disease progression. Use of antiplatelet agents and a platelet count ≥1500 × 109/L did not correlate with bleeding risk. Few studies have looked exclusively at young patients with ET. In this group, most patients were asymptomatic and well, ET being diagnosed incidentally. They were predominantly at low risk for thrombosis and other ET-related complications. The period of follow up was comparable to that of other studies and during that time, the rate of complications and risk of disease progression was low. The thrombosis rate of 0. 39% per patient year was less than that reported by other groups (2. 2–2. 6 thromboses/100patients/year) (Leukaemia 2007;21:1218–1223, Clin Appl Thrombosis/Hemostasis 2000;6(1):31–35) but similar to the 0. 74%/patient year reported by Barbui (Blood. Epub. June 13 2012). Overall findings generally complemented those reported by other groups. No risk factors were found to influence the occurrence of complications, but the number of events was small. Follow up of this group of patients over time is essential to see if their disease course remains benign or if complications will increase with time. Soli Deo Gloria Disclosures: Kam: Shire Pharmaceuticals: Consultancy, grant to support the MPN registry Other.

Calreticulin Mutation Does Not Modify the International Prognostic Score for Predicting the Risk of Thrombosis Among 1,150 Patients with Essential Thrombocythemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 404-404
Author(s):  
Guido Finazzi ◽  
Alessandra Carobbio ◽  
Paola Guglielmelli ◽  
Elisa Rumi ◽  
Silvia Salmoiraghi ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Prognostic Score ◽  
Low Risk ◽  
Intermediate Risk ◽  
Thrombotic Risk ◽  
Exon 9 ◽  
International Prognostic Score ◽  
Risk Categories ◽  
Calr Mutation

Abstract Background An International Prognostic Score for the risk of thrombosis (IPSET-thrombosis) in Essential Thrombocythemia (ET) was developed (Barbui et al. Blood, 2012;120:5128). Risk factors included: age >60 years (1 point), cardiovascular (CV) risk factors (1 point), previous thrombosis (2 points) and the presence of JAK2V617F mutation (2 points). Low, intermediate and high risk categories were identified by scores 0-1; 2; and ≥ 3, respectively. Mutations in the exon 9 of CALreticulin (CALR) gene were recently identified in about 50-60% of patients with JAK2V617F negative ET and associated with a reduced thrombotic risk as compared with JAK2V617F positive patients. Aim To evaluate whether the identification of CALRmutation in patients with ET has any impact on the IPSET-thrombosis score Patients and Methods Under the auspices of AGIMM (AIRC Gruppo Italiano Malattie Mieloproliferative), four Italian centers with recognized experience in myeloproliferative neoplasms participated in the current study. Overall, 1,150 patients who met the 2008 WHO criteria for ET and were molecularly characterized for JAK2V617F, MPLW515L/K and CALR exon 9 mutations were included. The JAK2 and MPL mutations were assessed by real-time quantitative polymerase chain reaction and by high-resolution melting analysis followed by bidirectional Sanger sequencing. Mutations in exon 9 of CALRwere assessed by bidirectional sequencing or next generation sequencing. Results Presenting features of the study population were: median age 58 years (range 5th-95th percentile 27-82 years; 65% females), median hemoglobin 14.1 g/dL (range 5th-95th percentile 11.8-16.3), median leukocyte count 8.7x109/L (range 5th-95th percentile 5.4-14.7), median platelet count 718x109/L (range 5th-95th percentile 486-1313). CV risk factors (at least one among smoke, diabetes and hypertension) were present in 568 (49%) patients. Arterial or venous thrombosis history before or at diagnosis was documented in 167 (15%) patients. JAK2V17F, MPLW515L/K and CALRmutations were detected in 744 (65%), 44 (4%) and 164 (14%) patients respectively. The remaining 198 patients (17%) were wild-type for all three mutations. During a median follow-up of 4.1 years (range 0-29), 104 patients developed an arterial or venous thrombotic event, with a total incidence rate of 1.59% patients/year (pt-ys). The IPSET-thrombosis ability to discriminate the thrombotic risk was confirmed. In fact, in the low risk (reference category), the rate was 0.57% pt-ys; in the intermediate risk was 1.60% pt-ys (Hazard Ratio (HR) 3.10, 95% Confidence Interval (CI) 1.55-6.18, p=0.001) and in the high risk group was 2.34% pts-yr (HR 4.59, 95% CI 2.41-8.77 p<0.0001). As to the impact of CALR mutation in the three categories of the IPSET-thrombosis score, we observed that CALR mutated patients were more frequently distributed in the low risk (48%) and intermediate risk (46%) than in the high risk IPSET groups (6%). In univariate analysis, patients carrying CALR mutation had a lower incidence of thrombosis than those with JAK2V617F (HR 0.61, 95% CI 0.34-1.09, p=0.093). However, CALR mutated patients were significantly younger (median age 53.5 versus 60.8 years, p=0.001) and presented with less previous thrombosis (8% versus 17%, p=0.005) than JAK2V617F mutated patients. This could explain why in multivariable models, CALR mutation did not retain the association with the risk of thrombosis. This was demonstrated in the whole population (HR 0.81, 95% CI 0.30-2.17, p=0.674), as well as in the low risk (HR 1.01, range 0.27-3.81, p=0.987) and intermediate risk categories (HR 1.80, range 0.57-5.72, p=0.317); the high risk category was not evaluable for the low proportion of CALRmutated patients in this group. Conclusions CALR mutation does not have a significant impact on the IPSET-thrombosis prognostic score. The score can be used as it is to predict the risk of thrombosis in molecularly-annotated, WHO-2008 diagnosed ET patients. Disclosures Vannucchi: Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Research Funding.

scholarly journals The Effects of Different Exercise Modalities in the Treatment of Cardiometabolic Risk Factors in Obese Adolescents with Sedentary Behavior—A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Children ◽  
2021 ◽  
Vol 8 (11) ◽  
pp. 1062
Author(s):  
Daxin Li ◽  
Ping Chen
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
High Risk ◽  
Sedentary Behavior ◽  
Cardiometabolic Risk ◽  
Meta Analysis ◽  
Cardiometabolic Risk Factors ◽  
Controlled Trials ◽  
Obese Adolescents ◽  
Randomized Controlled

Purpose: Obesity has become increasingly prevalent in adolescents due to unhealthy diet habits, sedentary behavior and a lack of physical activities. This study aims to assess the effects of different exercise modalities in the treatment of cardiometabolic risk factors (CRF) in obese adolescents with sedentary behavior. Methods: A systematic search was conducted using databases (PubMed, Embase, Cochrane library, Web of Science, CNKI and VIP database) from the earliest available date to August 2021. Nineteen randomized controlled trials (RCTs) with 704 participants were included. The included studies were evaluated for methodological quality by the Cochrane bias risk assessment tool, and a statistical analysis was performed by the Review Manage 5.3 and Stata 15.1 software. Results: The results of the meta-analysis showed that exercise could significantly improve obese adolescents’ body mass index (BMI) (MD = −1.99, 95% CI: −2.81 to −1.17, p < 0.00001), low density liptein cholesterol (LDL-C) (SMD = −0.98, 95% CI: −1.58 to −0.37, p = 0.002), triglyceride (TG) (SMD = −0.93, 95% CI: −1.72 to −0.14, p = 0.02), total cholesterol (TC) (SMD = −1.00, 95% CI: −1.73 to −0.26, p = 0.008), peak oxygen uptake (VO2peak) (MD = 3.27, 95% CI: 1.52 to 5.02, p = 0.0003) and homeostatic model assessment insulin resistance (HOMA-IR) (SMD = −2.07, 95% CI: −3.3 to −0.84, p = 0.001). However, there was no statistically significant difference in high-density liptein cholesterol (HDL-C) (SMD = 0.40, 95% CI: −0.28 to 1.08, p = 0.25). Conclusion: Exercise can effectively improve cardiometabolic risk factors in obese adolescents with sedentary behavior. For obese adolescents who want to lose weight and improve cardiorespiratory fitness, combined aerobic and resistance training and high-intensity interval training are optimal choices. For obese adolescents with high blood lipids, aerobic training can be regarded as a primary exercise modality to reduce the high risk of cardiovascular diseases; For obese adolescents with insulin resistance, combined aerobic and resistance training can be considered to reduce the high risk of diabetes. It is hoped that more high-quality studies will further expand the meta-analysis results and demonstrate the optimal exercise frequency and treatment intensity of cardiometabolic risk factors in obese adolescents with sedentary behavior in the future.

Abstract 18572: Sleep Duration is Associated with Degree of Insulin Resistance in a High Risk Population: the Baptist Employee Healthy Heart Study

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Shozab S Ali ◽  
Ebenezer Oni ◽  
Ehimen C Aneni ◽  
Lara Roberson ◽  
Janisse Post ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
High Risk ◽  
Cholesterol Level ◽  
Sleep Duration ◽  
High Risk Population ◽  
Risk Population ◽  
Heart Study ◽  
The Mean

Introduction: Metabolic syndrome, the clustering of multiple cardiovascular risk factors, is established as a risk factor for CVD. Shorter or longer sleep duration has been reported to be associated with increased risk of metabolic syndrome (MS) and diabetes mellitus (DM) through increased insulin resistance (IR). However, it is not known if impaired sleep alters IR in a high-risk population with known MS/DM. Methods: The Baptist Employee Healthy Heart Study is an ongoing lifestyle intervention study examining the effects of web-based interventions on reducing CVD risk in individuals with MS/DM. Sleep duration was self reported by the participants. Daily sleep duration was categorized into sleep <7 hours (short), 7 to 8 hours (normal) and >8 hours (long). Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated from fasting insulin and fasting glucose level. Results: The population consisted of 182 participants (74% women, 49% Hispanic, mean age 52 ± 9 years). In this study the mean sleep duration was 7±5 hours and mean HOMA-IR was 5.2 ± 5.6 units. Systolic and diastolic blood pressure, BMI, waist circumference, total cholesterol level and LDL cholesterol level did not apparently differ across the groups. Both short and long sleepers tended to have lower HDL cholesterol level and higher triglyceride level (p<0.05). The mean HOMA-IR was significantly higher in short and long sleepers {7-8hrs (4.09±4.8); <7hrs (5.36±4.7); >8hrs (9.52±10.7), p<0.001}, and were more likely to have HOMA-IR in the highest quartile as compared to normal sleepers. In ordinal logistic regression, after adjustment for traditional risk factors, short and long sleepers were at 2-3 fold higher risk of increasing levels of HOMA-IR. Conclusions: In this study of high metabolic risk individuals, sleep duration was associated with increased insulin resistance and highlights the importance of improving sleep hygiene in the clinical management of high risk individuals with MS and DM.

Obstetric antiphospholipid syndrome: still a challenge

Lupus ◽  
2010 ◽  
Vol 19 (4) ◽  
pp. 457-459 ◽  
Author(s):  
RA Levy ◽  
GRR Jesús ◽  
NR Jesús
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Antiphospholipid Syndrome ◽  
Fetal Death ◽  
Obstetric Complications ◽  
Premature Delivery ◽  
Thrombotic Risk ◽  
Recurrent Abortions ◽  
Obstetric Antiphospholipid Syndrome

Obstetric complications such as fetal death, premature delivery, preeclampsia and recurrent abortions (since chromosomal or anatomic defects have been excluded) are characteristic manifestations of antiphospholipid syndrome (APS). They can occur in patients with known APS with previous arterial or venous events in any tissue or organ, or be its first and only manifestation. Pregnancy in a patient with APS is considered high risk and the full prenatal clinical follow-up must be carried with this in mind, eliminating or minimizing concomitant thrombotic risk factors.

scholarly journals JAK2V617F Variant Allele Frequency Identifies Patients with Polycythemia Vera (PV) at High Risk for Venous Thrombosis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1776-1776
Author(s):  
Paola Guglielmelli ◽  
Giacomo Coltro ◽  
Giuseppe Gaetano Loscocco ◽  
Benedetta Sordi ◽  
Francesco Mannelli ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Venous Thrombosis ◽  
Allele Frequency ◽  
Variant Allele ◽  
Continuous Variables ◽  
Variant Allele Frequency ◽  
Thrombotic Risk ◽  
History Of ◽  
The Impact

Abstract Background. Cardiovascular (CV) events are leading cause of morbidity and mortality in PV. Current risk stratification is based on variables predicting thrombotic risk, ie age >60y and history of thrombosis. Recent studies focused on additional thrombotic risk factors in PV, including generic CV factors and leukocytosis. PV patients (pts) are JAK2V617F mutated, and present wide heterogeneity in variant allele frequency (VAF); it was shown that a VAF >75% was associated with higher number of thrombotic events after diagnosis (Vannucchi AM, Leukemia 2007), but the prognostic role of JAK2 VAF is still debated. Aim. The aim of the study was to evaluate the impact of JAK2V617F VAF on rate of thrombosis in WHO-2016 defined PV pts. Patients and Method. In the CRIMM (Florence) database, a total of 577 pts with a JAK2VF VAF determined within 3 years from diagnosis, who met the 2016 WHO criteria for PV, were identified. All pts had information regarding thromboembolic events, including history of thrombosis, occurrence, type and date of thrombosis in the follow-up (FU) and presence of CV risk factors (smoking, hypertension, and diabetes mellitus). Thrombosis‐free survival (TFS) was determined from the time of diagnosis to the time the first thrombotic event occurred. Pts in whom thrombosis did not occur were censored at the time of last FU. Pre-receiver operating characteristic (ROC) plots were used to determine cutoff levels for continuous variables of interest. Differences in the distribution of continuous variables between categories were analyzed by Mann-Whitney or Kruskal-Wallis test. Pts' groups with nominal variables were compared by χ2 test. TFS was estimated by Kaplan Meier analysis; log rank test was used to compare TFS difference between groups. Cox proportional hazards regression was used for multivariable analysis. A two tailed P ≤ 0.05 was considered statistically significant. Results. The median age of pts at diagnosis was 61y, 308 (53.4%) were above 60y; 57.2% were males. All pts were mutated for JAK2V617F with a median VAF 43% (range 1-100%), 62% had at least one CV risk factor; 83 (14.4%) pts suffered from an episode of thrombosis within 3 yr from, or coincident with, diagnosis. The median FU was 7.3y (0.6-35.9y) during which 87 pts (15.1%) developed thrombosis. (50 arterial and 45 venous thrombosis). During the FU, 110 pts (19.1%) died. A JAK2VAF of ≥60% cutoff level, as determined by ROC analysis, correlated with measurements of stimulated erythropoiesis (higher hematocrit, lower mean cell volume and serum ferritin; all P<.01), leukocytosis (P<.0001), lower platelets count (P=.02) and elevated serum lactate dehydrogenase (LDH) (P<.03). Pts with ≥60% JAK2V617F VAF were at higher relative risk (RR) of having splenomegaly (RR 3.1; P<0.001), suffering from pruritus (RR 2.5; P<0.001) or constitutional symptoms (RR 1.9; P=0.01), harboring a BM fibrosis grade-1 (RR 3.1; P<0.001). Additionally, pts with a VAF>60% had greater risk to progress to PPV-MF (RR 8.5, P<.0001) and acute leukemia (RR 4.4, P=0.04) or to die (RR 3.8, P<0.0001). The JAK2VF VAF (continuous or ≥60%) did not correlate with occurrence of thrombosis at diagnosis, while the rate of thrombosis during FU was significantly increased in pts with VAF ≥60% (23.4% vs 11.0%, RR 2.4, 95%CI = 1.4-4.0; P<0.0001), more marked for venous (RR 3.7, 95%CI = 2.0-6.8; P<0.0001) than arterial (RR 1.8, 95%CI = 0.9-3.3; P=0.05) thrombosis. The impact of VAF on thrombosis during FU was then estimated according to the conventional risk category. In low risk pts (LR) (n=236), factors significantly associated with occurrence of FU thrombosis were CV risk factors (dyslipidemia (RR 3.3, P = 0.02) and hypertension (RR 1.8, P=0.048)), a G1 BM fibrosis (RR 5.3, P=0.006), presence of splenomegaly (RR, 3.2, P=0.001) or constitutional symptoms (RR 3.3, P=0.003) and a VAF ≥60% (RR 2.2, P = 0.024). In high risk pts (HR) (n=341), factors significant for FU thrombosis were splenomegaly (RR 2.0, P=0.03), elevated LDH (RR 4.0, P=0.009) and a VAF ≥60% (RR 2.3, P = 0.012). A VAF ≥60% was correlated with shortened venous TFS after diagnosis in HR (P = 0.01, HR = 3.2, 95%CI = 1.2−8.3; fig.) but not in LR pts (P = 0.20, HR = 1.1, 95%CI = 0.5−2.9). Conclusions. This study indicates that conventionally-defined high-risk PV pts with a JAK2V617F VAF ≥60% suffer from increased rate of venous events and might be worthwhile of more intensive antithrombotic prophylaxis. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals Acute Ischemic Events in Patient Receiving Direct Oral Anticoagulants for Atrial Fibrilation: Incidence, Outcome and Clinical Profile

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1442-1442 ◽  
Author(s):  
Pável Olivera ◽  
Olga Gavin ◽  
Eugènia Rivero ◽  
Mireia Constans ◽  
Crisitina Marzo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
High Risk ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Therapeutic Failure ◽  
Clinical Profile ◽  
Thrombotic Risk ◽  
Ischemic Event ◽  
Ischemic Events

Abstract Introduction The use of direct oral anticoagulants (DOACs) is increasing for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Despite the good efficacy/safety balance, clinicians will be confronted with patients under treatment with DOAC presenting with ischemic events. Currently, there is a paucity of data from investigational studies regarding the clinical profile, risk factors and most suitable therapeutic intervention after therapeutic failure with these anticoagulants. Aims To describe the clinical profile and assess the rate of subsequent ischemic events appearing during the course of anticoagulant therapy and tried to identify risk factors for these events in "real life" population treated with DOACs. Methods In this multicenter and retrospective study we included patients with NVAF who had recived DOACs. Ischemic Events during february 2013 to february 2016 was analyzed. Results We enrolled, 3353 patients with NVAF who had recived DOACs. During the course of anticoagulation (mean, 9.4 months), 39 patients (1.16%) developed ischemic events (stroke, 22; transient ischemic attack (TIA), 7; peripheral embolism, 10). Rate of ischemic events was 0.9/100 patient-years. Median age was 76 years (range: 51-92) and 25 (64.1%) were female. Among them, 19 patients received dabigatran, 14 rivaroxaban and 6 apixaban. As per the thrombotic risk score, 66.7% of the patients were classified as "high risk" (CHA2DS2-VASc score > 5). Thirty-eight patients (97.4%) received vitamin K antagonists (VKA) prior to use of DOAC. Ischemic events patients had a higher incidence of hypertention (94.9% ), diabetes (64.1%), history of previous ischemic stroke (74.4%) and therapeutic failure with VKA (79.5%). Nonadherence to treatment was identified only in 6 patients (15.4%). On multivariable analysis, previous ischemic stroke/ TIA (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.21-2.61), female sex (HR, 1.54; 95% CI, 1.05-2.26), and CHA2DS2-VASc score>5 (HR, 1.72; 95% CI, 1.25-2.36) were independently associated with the risk for ischemic events. For the management of acute ischemic event, 20 patients received endovascular treatment, 12 patients switched from DOAC to unfractionated heparin or low molecular weight heparin and intravenous fibrinolysis was performed in 7 patients; intracranial hemorrhage being observed in two patients after treatment with thrombolytic therapy. Regarding the subsequent anticoagulation continuation at discharge, 19 patients switched to concomitant therapy with DOAC and antiplatelets, 12 patients to other DOAC and only 8 to VKA. There was a 5.1% 30 day mortality after ischemic event and 15.4% of patients had neurologic complications after ischemic event. Conclusions We described a low rate of stroke in patients treated with DOACs, but further studies are necessary in order to identify very high-risk patients with special emphasis in those with high CHA2DS2-VASC score, previous stroke and a correct anticoagulation. Disclosures No relevant conflicts of interest to declare.

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