Hemorrhagic Transformation in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Time to Initiation of Oral Anticoagulant Therapy and Outcomes.

Background In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation ( HT ). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT , (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT . Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3-8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0-6.0) of those without HT ; 53.1% of patients with  HT were deceased or disabled compared with 35.8% of those without HT . On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24-2.35). Conclusions In patients with HT , anticoagulation was initiated about 12 days later than patients without HT . This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability

Randomized, double-blind, placebo-controlled study on the antihypertensive effects of Grana Padano D.O.P. cheese consumption in mild-moderate hypertensive subjects

OBJECTIVE: Grana Padano, an Italian protected designation of origin (PDO) semi-fat cheese, undergoes a long ripening period during which the proteolysis carried out by natural starter lactic acid bacteria releases peptides having sustained angiotensin-converting enzyme (ACE)-inhibitory activity. The length (generally 3-8 amino acid residues) and the sequence of these peptides are responsible for their ability to elicit ACE-inhibitory activity. The aim of this study has been the evaluation of the effect of a daily dietary supplement consisting in a small amount (30 g/day) of Grana Padano cheese, in terms of the lowering of the blood pressure (BP) of mild-moderate hypertensive subjects. PATIENTS AND METHODS: Thirty mild-moderate hypertensive patients, with BP values not on target (> 140 and/or > 90 mmHg) after at least 3 months of stable treatment were considered in this randomized, double-blind placebo-controlled cross-over study. All patients randomly received a dietary integration (30 g/day) of Grana Padano cheese or a placebo (made from flavored grated bread mixed with fats and salts in concentrations equal to those of the cheese). BP was evaluated at baseline and at the end of the active and placebo treatments (2 months each) by: - Office BP (OBP); - Automated Office BP (AOBP) using the BpTRU\uae, an automated oscillometric device that provides the average of multiple (n=6) blood pressure measurements; - Ambulatory Blood Pressure (ABP) 24 hour monitoring. RESULTS: Dietary integration with Grana Padano cheese resulted in a significant decrease in Office, Automated Office and Ambulatory BP. The mean decrease (vs. placebo) for 24-hour ABP was -3.5 mmHg for systolic and -2.4 mmHg for diastolic BP (p = 0.0063 and p = 0.0065, respectively). CONCLUSIONS: Daily dietary integration with 30 g of Grana Padano DOP cheese effectively reduces BP and may help mild-to-moderate hypertensive patients to reach a target BP

Randomized, double-blind placebo-controlled pilot study of the antihypertensive effects of Grana Padano D.O.P. cheese consumption in mild - moderate hypertensive subjects.

OBJECTIVE: Grana Padano, an Italian protected designation of origin (PDO) semi-fat cheese, undergoes a long ripening period during which the proteolysis carried out by natural starter lactic acid bacteria releases peptides having sustained angiotensin-converting enzyme (ACE)-inhibitory activity. The length (generally 3-8 amino acid residues) and the sequence of these peptides are responsible for their ability to elicit ACE-inhibitory activity. The aim of this study has been the evaluation of the effect of a daily dietary supplement consisting in a small amount (30 g/day) of Grana Padano cheese, in terms of the lowering of the blood pressure (BP) of mild - moderate hypertensive subjects. PATIENTS AND METHODS: Thirty mild – moderate hypertensive patients, with BP values not on target (> 140 and/or > 90 mmHg) after at least 3 months of stable treatment were considered in this randomized, double-blind placebo-controlled cross-over study. All patients randomly received a dietary integration (30 g/day) of Grana Padano cheese or a placebo (made from flavored grated bread mixed with fats and salts in concentrations equal to those of the cheese). BP was evaluated at baseline and at the end of the active and placebo treatments (2 months each) by: – Office BP (OBP); – Automated Office BP (AOBP) using the BpTRU ®, an automated oscillometric device that provides the average of multiple (n=6) blood pressure measurements; – Ambulatory Blood Pressure (ABP) 24 hour monitoring. RESULTS: Dietary integration with Grana Padano cheese resulted in a significant decrease in Office, Automated Office and Ambulatory BP. The mean decrease (vs. placebo) for 24-hour ABP was –3.5 mmHg for systolic and –2.4 mmHg for diastolic BP (p = 0.0063 and p = 0.0065, respectively). CONCLUSIONS: Daily dietary integration with 30 g of Grana Padano DOP cheese effectively reduces BP and may help mild-to-moderate hypertensive patients to reach a target BP

Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)

Introduction: Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes. Methods: Data were analyzed from the \u201cRecurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation\u201d (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0\u20132 favorable outcome, 3\u20136 unfavorable outcome). Results: Of the 1029 patients enrolled, 561 were women (54.5%) (p < 0.001) and younger (p < 0.001) compared to men. In patients with known atrial fibrillation, women were less likely to receive oral anticoagulants before index stroke (p = 0.026) and were less likely to receive anticoagulants after stroke (71.3% versus 78.4%, p = 0.01). There was no observed sex difference regarding the time of starting anticoagulant therapy between the two groups (6.4 \ub1 11.7 days for men versus 6.5 \ub1 12.4 days for women, p = 0.902). Men presented with more severe strokes at onset (mean NIHSS 9.2 \ub1 6.9 versus 8.1 \ub1 7.5, p < 0.001). Within 90 days, 46 (8.2%) recurrent ischemic events (stroke/TIA/systemic embolism) and 19 (3.4%) symptomatic cerebral bleedings were found in women compared to 30 (6.4%) and 18 (3.8%) in men (p = 0.28 and p = 0.74). At 90 days, 57.7% of women were disabled or deceased, compared to 41.1% of the men (p < 0.001). Multivariate analysis did not confirm this significance. Conclusions: Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes

Prestroke CHA2DS2-VASc Score and Severity of Acute Stroke in Patients with Atrial Fibrillation: Findings from RAF Study.

The aim of this study was to investigate for a possible association between both prestroke CHA2DS2-VASc score and the severity of stroke at presentation, as well as disability and mortality at 90 days, in patients with acute stroke and atrial fibrillation (AF). This prospective study enrolled consecutive patients with acute ischemic stroke, AF, and assessment of prestroke CHA2DS2-VASc score. Severity of stroke was assessed on admission using the National Institutes of Health Stroke Scale (NIHSS) score (severe stroke: NIHSS ≥10). Disability and mortality at 90 days were assessed by the modified Rankin Scale (mRS <3 or ≥3). Multiple logistic regression was used to correlate prestroke CHA2DS2-VASc and severity of stroke, as well as disability and mortality at 90 days. Of the 1020 patients included in the analysis, 606 patients had an admission NIHSS score lower and 414 patients higher than 10. At 90 days, 510 patients had mRS ≥3. A linear correlation was found between the prestroke CHA2DS2-VASc score and severity of stroke (P = .001). On multivariate analysis, CHA2DS2-VASc score correlated with severity of stroke (P = .041) and adverse functional outcome (mRS ≥3) (P = .001). A logistic regression with the receiver operating characteristic graph procedure (C-statistics) evidenced an area under the curve of .60 (P = .0001) for severe stroke. Furthermore, a correlation was found between prestroke CHA2DS2-VASc score and lesion size. In patients with AF, in addition to the risk of stroke, a high CHA2DS2-VASc score was independently associated with both stroke severity at onset and disability and mortality at 90 days

Efficacy of rivaroxaban for thromboprophylaxis after knee arthroscopy (ERIKA): A phase ii, multicentre, double-blind, placebo-controlled randomised study

Without thromboprophylaxis, knee arthroscopy (KA) carries a low to moderate risk of venous thromboembolism. Over 5 million arthroscopies are performed worldwide yearly. It was our study objective to assess the efficacy and safety of rivaroxaban for thromboprophylaxis after therapeutic KA. Patients undergoing KA in nine Italian teaching or community hospitals were allocated to once-daily rivaroxaban (10 mg) or placebo for seven days in a phase II, multicentre, double-blind, placebo-controlled randomised trial. The primary efficacy outcome was a composite of all-cause death, symptomatic thromboembolism and asymptomatic proximal DVT at three months; major bleeding represented the primary safety outcome. All patients underwent whole-leg ultrasonography at day 7(+1), or earlier if symptomatic. A total of 241 patients were randomised (122 rivaroxaban, 119 placebo), and 234 completed the study. The primary efficacy outcome occurred in 1/120 of the rivaroxaban group and in 7/114 of the placebo group (0.8% vs 6.1%, respectively, p=0.03; absolute risk difference, -5.3%, 95 °% CI, -11.4 to -0.8; crude relative risk 0.14, 95%> CI, 0.02 to 0.83; number-needed-to-treat=19). No major bleedings were observed. We found no association between different arthroscopic procedures and thrombotic events. Small sample size, high exclusion rate, and low number of anterior cruciate ligament reconstruction procedures are the main limitations of our study. In conclusion, a seven-day course of 10-mg rivaroxaban may be safely employed for thromboprophylaxis after KA. Whether prophylaxis after KA should be given to all patients, or to selected "high-risk" subjects, remains to be determined. A larger trial to verify our preliminary results is warranted

Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)

Introduction: Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes. Methods: Data were analyzed from the “Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation” (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0–2 favorable outcome, 3–6 unfavorable outcome). Results: Of the 1029 patients enrolled, 561 were women (54.5%) (p < 0.001) and younger (p < 0.001) compared to men. In patients with known atrial fibrillation, women were less likely to receive oral anticoagulants before index stroke (p = 0.026) and were less likely to receive anticoagulants after stroke (71.3% versus 78.4%, p = 0.01). There was no observed sex difference regarding the time of starting anticoagulant therapy between the two groups (6.4 ± 11.7 days for men versus 6.5 ± 12.4 days for women, p = 0.902). Men presented with more severe strokes at onset (mean NIHSS 9.2 ± 6.9 versus 8.1 ± 7.5, p < 0.001). Within 90 days, 46 (8.2%) recurrent ischemic events (stroke/TIA/systemic embolism) and 19 (3.4%) symptomatic cerebral bleedings were found in women compared to 30 (6.4%) and 18 (3.8%) in men (p = 0.28 and p = 0.74). At 90 days, 57.7% of women were disabled or deceased, compared to 41.1% of the men (p < 0.001). Multivariate analysis did not confirm this significance. Conclusions: Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes. © 2016, © European Stroke Organisation 2016

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study

The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke

Safety of Anticoagulation in Patients Treated with Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation

Background and Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either Vitamin K antagonists or nonVitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02]). Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant. © 2020 The Authors

Safety of Anticoagulation in Patients Treated with Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation

92noneBackground and Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either Vitamin K antagonists or nonVitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02]). Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant.noneGiustozzi M.; Acciarresi M.; Agnelli G.; Caso V.; Bandini F.; Tsivgoulis G.; Yaghi S.; Furie K.L.; Tadi P.; Becattini C.; Zedde M.; Abdul-Rahim A.H.; Lees K.R.; Alberti A.; Venti M.; D'Amore C.; Giulia Mosconi M.; Anna Cimini L.; Bovi P.; Carletti M.; Rigatelli A.; Cappellari M.; Putaala J.; Tomppo L.; Tatlisumak T.; Marcheselli S.; Pezzini A.; Poli L.; Padovani A.; Vannucchi V.; Sohn S.-I.; Lorenzini G.; Tassi R.; Guideri F.; Acampa M.; Martini G.; Ntaios G.; Athanasakis G.; Makaritsis K.; Karagkiozi E.; Vadikolias K.; Liantinioti C.; Theodorou A.; Halvatsiotis P.; Mumoli N.; Galati F.; Sacco S.; Tiseo C.; Corea F.; Ageno W.; Bellesini M.; Silvestrelli G.; Ciccone A.; Lanari A.; Scoditti U.; Denti L.; Mancuso M.; Ferrari E.; Ulivi L.; Orlandi G.; Giannini N.; Tassinari T.; Luisa De Lodovici M.; Rueckert C.; Baldi A.; Toni D.; Letteri F.; Giuntini M.; Maria Lotti E.; Flomin Y.; Pieroni A.; Kargiotis O.; Karapanayiotides T.; Monaco S.; Maimone Baronello M.; Csiba L.; Szabo L.; Chiti A.; Giorli E.; Del Sette M.; Imberti D.; Zabzuni D.; Doronin B.; Volodina V.; Michel P.; Vanacker P.; Barlinn K.; Barlinn J.; Deleu D.; Gourbali V.; Paciaroni M.; Masotti L.Giustozzi, M.; Acciarresi, M.; Agnelli, G.; Caso, V.; Bandini, F.; Tsivgoulis, G.; Yaghi, S.; Furie, K. L.; Tadi, P.; Becattini, C.; Zedde, M.; Abdul-Rahim, A. H.; Lees, K. R.; Alberti, A.; Venti, M.; D'Amore, C.; Giulia Mosconi, M.; Anna Cimini, L.; Bovi, P.; Carletti, M.; Rigatelli, A.; Cappellari, M.; Putaala, J.; Tomppo, L.; Tatlisumak, T.; Marcheselli, S.; Pezzini, A.; Poli, L.; Padovani, A.; Vannucchi, V.; Sohn, S. -I.; Lorenzini, G.; Tassi, R.; Guideri, F.; Acampa, M.; Martini, G.; Ntaios, G.; Athanasakis, G.; Makaritsis, K.; Karagkiozi, E.; Vadikolias, K.; Liantinioti, C.; Theodorou, A.; Halvatsiotis, P.; Mumoli, N.; Galati, F.; Sacco, S.; Tiseo, C.; Corea, F.; Ageno, W.; Bellesini, M.; Silvestrelli, G.; Ciccone, A.; Lanari, A.; Scoditti, U.; Denti, L.; Mancuso, M.; Ferrari, E.; Ulivi, L.; Orlandi, G.; Giannini, N.; Tassinari, T.; Luisa De Lodovici, M.; Rueckert, C.; Baldi, A.; Toni, D.; Letteri, F.; Giuntini, M.; Maria Lotti, E.; Flomin, Y.; Pieroni, A.; Kargiotis, O.; Karapanayiotides, T.; Monaco, S.; Maimone Baronello, M.; Csiba, L.; Szabo, L.; Chiti, A.; Giorli, E.; Del Sette, M.; Imberti, D.; Zabzuni, D.; Doronin, B.; Volodina, V.; Michel, P.; Vanacker, P.; Barlinn, K.; Barlinn, J.; Deleu, D.; Gourbali, V.; Paciaroni, M.; Masotti, L