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1. 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

Author

Paciaroni, M. Caso, V. Agnelli, G. Mosconi, M.G. Giustozzi, M. Seiffge, D.J. Engelter, S.T. Lyrer, P. Polymeris, A.A. Kriemler, L. Zietz, A. Putaala, J. Strbian, D. Tomppo, L. Michel, P. Strambo, D. Salerno, A. Remillard, S. Buehrer, M. Bavaud, O. Vanacker, P. Zuurbier, S. Yperzeele, L. Loos, C.M.J. Cappellari, M. Emiliani, A. Zedde, M. Abdul-Rahim, A. Dawson, J. Cronshaw, R. Schirinzi, E. Del Sette, M. Stretz, C. Kala, N. Reznik, M. Schomer, A. Grory, B.M. Jayaraman, M. Mctaggart, R. Yaghi, S. Furie, K.L. Masotti, L. Grifoni, E. Toni, D. Risitano, A. Falcou, A. Petraglia, L. Lotti, E.M. Padroni, M. Pavolucci, L. Lochner, P. Silvestrelli, G. Ciccone, A. Alberti, A. Venti, M. Traballi, L. Urbini, C. Kargiotis, O. Rocco, A. Diomedi, M. Marcheselli, S. Caliandro, P. Zauli, A. Reale, G. Antonenko, K. Rota, E. Tassinari, T. Saia, V. Palmerini, F. Aridon, P. Arnao, V. Monaco, S. Cottone, S. Baldi, A. D'Amore, C. Ageno, W. Pegoraro, S. Ntaios, G. Sagris, D. Giannopoulos, S. Kosmidou, M. Ntais, E. Romoli, M. Pantoni, L. Rosa, S. Bertora, P. Chiti, A. Canavero, I. Saggese, C.E. Plocco, M. Giorli, E. Palaiodimou, L. Bakola, E. Tsivgoulis, G. Bandini, F. Gasparro, A. Terruso, V. Mannino, M. Pezzini, A. Ornello, R. Sacco, S. Popovic, N. Scoditti, U. Genovese, A. Denti, L. Flomin, Y. Mancuso, M. Ferrari, E. Caselli, M.C. Ulivi, L. Giannini, N. De Marchis, G.M. and Paciaroni, M. Caso, V. Agnelli, G. Mosconi, M.G. Giustozzi, M. Seiffge, D.J. Engelter, S.T. Lyrer, P. Polymeris, A.A. Kriemler, L. Zietz, A. Putaala, J. Strbian, D. Tomppo, L. Michel, P. Strambo, D. Salerno, A. Remillard, S. Buehrer, M. Bavaud, O. Vanacker, P. Zuurbier, S. Yperzeele, L. Loos, C.M.J. Cappellari, M. Emiliani, A. Zedde, M. Abdul-Rahim, A. Dawson, J. Cronshaw, R. Schirinzi, E. Del Sette, M. Stretz, C. Kala, N. Reznik, M. Schomer, A. Grory, B.M. Jayaraman, M. Mctaggart, R. Yaghi, S. Furie, K.L. Masotti, L. Grifoni, E. Toni, D. Risitano, A. Falcou, A. Petraglia, L. Lotti, E.M. Padroni, M. Pavolucci, L. Lochner, P. Silvestrelli, G. Ciccone, A. Alberti, A. Venti, M. Traballi, L. Urbini, C. Kargiotis, O. Rocco, A. Diomedi, M. Marcheselli, S. Caliandro, P. Zauli, A. Reale, G. Antonenko, K. Rota, E. Tassinari, T. Saia, V. Palmerini, F. Aridon, P. Arnao, V. Monaco, S. Cottone, S. Baldi, A. D'Amore, C. Ageno, W. Pegoraro, S. Ntaios, G. Sagris, D. Giannopoulos, S. Kosmidou, M. Ntais, E. Romoli, M. Pantoni, L. Rosa, S. Bertora, P. Chiti, A. Canavero, I. Saggese, C.E. Plocco, M. Giorli, E. Palaiodimou, L. Bakola, E. Tsivgoulis, G. Bandini, F. Gasparro, A. Terruso, V. Mannino, M. Pezzini, A. Ornello, R. Sacco, S. Popovic, N. Scoditti, U. Genovese, A. Denti, L. Flomin, Y. Mancuso, M. Ferrari, E. Caselli, M.C. Ulivi, L. Giannini, N. De Marchis, G.M.

Abstract

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

Published
2022

2. Oral Anticoagulants in the Oldest Old with Recent Stroke and Atrial Fibrillation

Author

Polymeris, A.A. Macha, K. Paciaroni, M. Wilson, D. Koga, M. Cappellari, M. Schaedelin, S. Zietz, A. Peters, N. Seiffge, D.J. Haupenthal, D. Gassmann, L. De Marchis, G.M. Wang, R. Gensicke, H. Stoll, S. Thilemann, S. Avramiotis, N.S. Bonetti, B. Tsivgoulis, G. Ambler, G. Alberti, A. Yoshimura, S. Brown, M.M. Shiozawa, M. Lip, G.Y.H. Venti, M. Acciarresi, M. Tanaka, K. Mosconi, M.G. Takagi, M. Jäger, R.H. Muir, K. Inoue, M. Schwab, S. Bonati, L.H. Lyrer, P.A. Toyoda, K. Caso, V. Werring, D.J. Kallmünzer, B. Engelter, S.T. Engelter, S.T. Lyrer, P.A. Bonati, L.H. Seiffge, D.J. Traenka, C. Polymeris, A.A. Zietz, A. Peters, N. De Marchis, G.M. Thilemann, S. Avramiotis, N.S. Gensicke, H. Hert, L. Wagner, B. Schaub, F. Meya, L. Fladt, J. Dittrich, T. Fisch, U. Macha, K. Haupenthal, D. Gassmann, L. Wang, R. Stoll, S. Schwab, S. Volbers, B. Siedler, G. Kallmünzer, B. Cappellari, M. Bonetti, B. Bovi, P. Tomelleri, G. Micheletti, N. Zivelonghi, C. Emiliani, A. Parry-Jones, A. Patterson, C. Price, C. Elmarimi, A. Parry, A. Nallasivam, A. Nor, A.M. Esis, B. Bruce, D. Bhaskaran, B. Roffe, C. Cullen, C. Holmes, C. Cohen, D. Hargroves, D. Mangion, D. Chadha, D. Vahidassr, D. Manawadu, D. Giallombardo, E. Warburton, E. Flossman, E. Gunathilagan, G. Proschel, H. Emsley, H. Anwar, I. Burger, I. Okwera, J. Putterill, J. O’Connell, J. Bamford, J. Corrigan, J. Scott, J. Birns, J. Kee, K. Saastamoinen, K. Pasco, K. Dani, K. Sekaran, L. Choy, L. Iveson, L. Mamun, M. Sajid, M. Cooper, M. Burn, M. Smith, M. Power, M. Davis, M. Smyth, N. Veltkamp, R. Sharma, P. Guyler, P. O’Mahony, P. Wilkinson, P. Datta, P. Aghoram, P. Marsh, R. Luder, R. Meenakishundaram, S. Subramonian, S. Leach, S. Ispoglou, S. Andole, S. England, T. Manoj, A. Harrington, F. Rehman, H. Sword, J. Staals, J. Mahawish, K. Harkness, K. Shaw, L. McCormich, M. Sprigg, N. Mansoor, S. Krishnamurthy, V. Giustozzi, M. Acciarresi, M. Agnelli, G. Becattini, C. Alberti, A. D’Amore, C. Cimini, L.A. Bandini, F. Tsivgoulis, G. Liantinioti and Polymeris, A.A. Macha, K. Paciaroni, M. Wilson, D. Koga, M. Cappellari, M. Schaedelin, S. Zietz, A. Peters, N. Seiffge, D.J. Haupenthal, D. Gassmann, L. De Marchis, G.M. Wang, R. Gensicke, H. Stoll, S. Thilemann, S. Avramiotis, N.S. Bonetti, B. Tsivgoulis, G. Ambler, G. Alberti, A. Yoshimura, S. Brown, M.M. Shiozawa, M. Lip, G.Y.H. Venti, M. Acciarresi, M. Tanaka, K. Mosconi, M.G. Takagi, M. Jäger, R.H. Muir, K. Inoue, M. Schwab, S. Bonati, L.H. Lyrer, P.A. Toyoda, K. Caso, V. Werring, D.J. Kallmünzer, B. Engelter, S.T. Engelter, S.T. Lyrer, P.A. Bonati, L.H. Seiffge, D.J. Traenka, C. Polymeris, A.A. Zietz, A. Peters, N. De Marchis, G.M. Thilemann, S. Avramiotis, N.S. Gensicke, H. Hert, L. Wagner, B. Schaub, F. Meya, L. Fladt, J. Dittrich, T. Fisch, U. Macha, K. Haupenthal, D. Gassmann, L. Wang, R. Stoll, S. Schwab, S. Volbers, B. Siedler, G. Kallmünzer, B. Cappellari, M. Bonetti, B. Bovi, P. Tomelleri, G. Micheletti, N. Zivelonghi, C. Emiliani, A. Parry-Jones, A. Patterson, C. Price, C. Elmarimi, A. Parry, A. Nallasivam, A. Nor, A.M. Esis, B. Bruce, D. Bhaskaran, B. Roffe, C. Cullen, C. Holmes, C. Cohen, D. Hargroves, D. Mangion, D. Chadha, D. Vahidassr, D. Manawadu, D. Giallombardo, E. Warburton, E. Flossman, E. Gunathilagan, G. Proschel, H. Emsley, H. Anwar, I. Burger, I. Okwera, J. Putterill, J. O’Connell, J. Bamford, J. Corrigan, J. Scott, J. Birns, J. Kee, K. Saastamoinen, K. Pasco, K. Dani, K. Sekaran, L. Choy, L. Iveson, L. Mamun, M. Sajid, M. Cooper, M. Burn, M. Smith, M. Power, M. Davis, M. Smyth, N. Veltkamp, R. Sharma, P. Guyler, P. O’Mahony, P. Wilkinson, P. Datta, P. Aghoram, P. Marsh, R. Luder, R. Meenakishundaram, S. Subramonian, S. Leach, S. Ispoglou, S. Andole, S. England, T. Manoj, A. Harrington, F. Rehman, H. Sword, J. Staals, J. Mahawish, K. Harkness, K. Shaw, L. McCormich, M. Sprigg, N. Mansoor, S. Krishnamurthy, V. Giustozzi, M. Acciarresi, M. Agnelli, G. Becattini, C. Alberti, A. D’Amore, C. Cimini, L.A. Bandini, F. Tsivgoulis, G. Liantinioti

Abstract

Objective: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years. Methods: Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (<3 months) aged ≥85 versus <85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all-cause death. We used simple, adjusted, and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk. Results: In total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged ≥85 years and 3,688 (62%) received a DOAC. During 6,874 patient-years follow-up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged ≥85 (HR≥85y = 0.65, 95%-CI [0.52, 0.81]) and < 85 years (HR<85y = 0.79, 95%-CI [0.66, 0.95]) in simple (pinteraction = 0.129), adjusted (pinteraction = 0.094) or weighted (pinteraction = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and < 85 years (+1.90 to +3.36 events/100 patient-years for ICH-weights 1.5 to 3.1). Interpretation: The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 2022;91:78–88. © 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

Published
2022

3. Aetiology of acute respiratory infection in preschool children requiring hospitalisation in Europe-results from the PED-MERMAIDS multicentre case-control study

Author

Vasconcelos, M.K. Loens, K. Sigfrid, L. Iosifidis, E. Epalza, C. Donà, D. Matheeussen, V. Papachristou, S. Roilides, E. Gijon, M. Rojo, P. Minotti, C. Da Dalt, L. Islam, S. Jarvis, J. Syggelou, A. Tsolia, M. Nyang'wa, M.N. Keers, S. Renk, H. Gemmel, A.-L. D'Amore, C. Atti, M.C.D. Sánchez, C.R.-T. Martinón-Torres, F. Burokiene, S. Goetghebuer, T. Spoulou, V. Riordan, A. Calvo, C. Gkentzi, D. Hufnagel, M. Openshaw, P.J. De Jong, M.D. Koopmans, M. Goossens, H. Ieven, M. Fraaij, P.L.A. Giaquinto, C. Bielicki, J.A. Horby, P. Sharland, M. and Vasconcelos, M.K. Loens, K. Sigfrid, L. Iosifidis, E. Epalza, C. Donà, D. Matheeussen, V. Papachristou, S. Roilides, E. Gijon, M. Rojo, P. Minotti, C. Da Dalt, L. Islam, S. Jarvis, J. Syggelou, A. Tsolia, M. Nyang'wa, M.N. Keers, S. Renk, H. Gemmel, A.-L. D'Amore, C. Atti, M.C.D. Sánchez, C.R.-T. Martinón-Torres, F. Burokiene, S. Goetghebuer, T. Spoulou, V. Riordan, A. Calvo, C. Gkentzi, D. Hufnagel, M. Openshaw, P.J. De Jong, M.D. Koopmans, M. Goossens, H. Ieven, M. Fraaij, P.L.A. Giaquinto, C. Bielicki, J.A. Horby, P. Sharland, M.

Abstract

Background Both pathogenic bacteria and viruses are frequently detected in the nasopharynx (NP) of children in the absence of acute respiratory infection (ARI) symptoms. The aim of this study was to estimate the aetiological fractions for ARI hospitalisation in children for respiratory syncytial virus (RSV) and influenza virus and to determine whether detection of specific respiratory pathogens on NP samples was associated with ARI hospitalisation. Methods 349 children up to 5 years of age hospitalised for ARI (following a symptom-based case definition) and 306 hospital controls were prospectively enrolled in 16 centres across seven European Union countries between 2016 and 2019. Admission day NP swabs were analysed by multiplex PCR for 25 targets. Results RSV was the leading single cause of ARI hospitalisations, with an overall population attributable fraction (PAF) of 33.4% and high seasonality as well as preponderance in younger children. Detection of RSV on NP swabs was strongly associated with ARI hospitalisation (OR adjusted for age and season: 20.6, 95% CI: 9.4 to 45.3). Detection of three other viral pathogens showed strong associations with ARI hospitalisation: influenza viruses had an adjusted OR of 6.1 (95% CI: 2.5 to 14.9), parainfluenza viruses (PIVs) an adjusted OR of 4.6 (95% CI: 1.8 to 11.3) and metapneumoviruses an adjusted OR of 4.5 (95% CI: 1.3 to 16.1). Influenza viruses had a PAF of 7.9%, PIVs of 6.5% and metapneumoviruses of 3.0%. In contrast, most other pathogens were found in similar proportions in cases and controls, including Streptococcus pneumoniae, which was weakly associated with case status, and endemic coronaviruses. Conclusion RSV is the predominant cause of ARI hospitalisations in young children in Europe and its detection, as well as detection of influenza virus, PIV or metapneumovirus, on NP swabs can establish aetiology with high probability. PAFs for RSV and influenza virus are highly seasonal and age dependent. © 2016 Georg Thi

Published
2021

4. Risk Factors for Intracerebral Hemorrhage in Patients with Atrial Fibrillation on Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention

Author

Paciaroni, M. Agnelli, G. Giustozzi, M. Caso, V. Toso, E. Angelini, F. Canavero, I. Micieli, G. Antonenko, K. Rocco, A. Diomedi, M. Katsanos, A.H. Shoamanesh, A. Giannopoulos, S. Ageno, W. Pegoraro, S. Putaala, J. Strbian, D. Sallinen, H. Mac Grory, B.C. Furie, K.L. Stretz, C. Reznik, M.E. Alberti, A. Venti, M. Mosconi, M.G. Vedovati, M.C. Franco, L. Zepponi, G. Romoli, M. Zini, A. Brancaleoni, L. Riva, L. Silvestrelli, G. Ciccone, A. Zedde, M.L. Giorli, E. Kosmidou, M. Ntais, E. Palaiodimou, L. Halvatsiotis, P. Tassinari, T. Saia, V. Ornello, R. Sacco, S. Bandini, F. Mancuso, M. Orlandi, G. Ferrari, E. Pezzini, A. Poli, L. Cappellari, M. Forlivesi, S. Rigatelli, A. Yaghi, S. Scher, E. Frontera, J.A. Masotti, L. Grifoni, E. Caliandro, P. Zauli, A. Reale, G. Marcheselli, S. Gasparro, A. Terruso, V. Arnao, V. Aridon, P. Abdul-Rahim, A.H. Dawson, J. Saggese, C.E. Palmerini, F. Doronin, B. Volodina, V. Toni, D. Risitano, A. Schirinzi, E. Del Sette, M. Lochner, P. Monaco, S. Mannino, M. Tassi, R. Guideri, F. Acampa, M. Martini, G. Lotti, E.M. Padroni, M. Pantoni, L. Rosa, S. Bertora, P. Ntaios, G. Sagris, D. Baldi, A. D'Amore, C. Mumoli, N. Porta, C. Denti, L. Chiti, A. Corea, F. Acciarresi, M. Flomin, Y. Popovic, N. Tsivgoulis, G. and Paciaroni, M. Agnelli, G. Giustozzi, M. Caso, V. Toso, E. Angelini, F. Canavero, I. Micieli, G. Antonenko, K. Rocco, A. Diomedi, M. Katsanos, A.H. Shoamanesh, A. Giannopoulos, S. Ageno, W. Pegoraro, S. Putaala, J. Strbian, D. Sallinen, H. Mac Grory, B.C. Furie, K.L. Stretz, C. Reznik, M.E. Alberti, A. Venti, M. Mosconi, M.G. Vedovati, M.C. Franco, L. Zepponi, G. Romoli, M. Zini, A. Brancaleoni, L. Riva, L. Silvestrelli, G. Ciccone, A. Zedde, M.L. Giorli, E. Kosmidou, M. Ntais, E. Palaiodimou, L. Halvatsiotis, P. Tassinari, T. Saia, V. Ornello, R. Sacco, S. Bandini, F. Mancuso, M. Orlandi, G. Ferrari, E. Pezzini, A. Poli, L. Cappellari, M. Forlivesi, S. Rigatelli, A. Yaghi, S. Scher, E. Frontera, J.A. Masotti, L. Grifoni, E. Caliandro, P. Zauli, A. Reale, G. Marcheselli, S. Gasparro, A. Terruso, V. Arnao, V. Aridon, P. Abdul-Rahim, A.H. Dawson, J. Saggese, C.E. Palmerini, F. Doronin, B. Volodina, V. Toni, D. Risitano, A. Schirinzi, E. Del Sette, M. Lochner, P. Monaco, S. Mannino, M. Tassi, R. Guideri, F. Acampa, M. Martini, G. Lotti, E.M. Padroni, M. Pantoni, L. Rosa, S. Bertora, P. Ntaios, G. Sagris, D. Baldi, A. D'Amore, C. Mumoli, N. Porta, C. Denti, L. Chiti, A. Corea, F. Acciarresi, M. Flomin, Y. Popovic, N. Tsivgoulis, G.

Abstract

Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non-vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA2DS2-VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA2DS2-VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA2DS2-VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468-0.525) and 0.530 (95% CI, 0.500-0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA2DS2-VASc scores. © 2021 Lippincott Williams and Wilkins. All rights reserved.

Published
2021

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

Author

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. Szabó, 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. and 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. Szabó, 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.

Abstract

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 (o

Published
2020

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

Author

Paciaroni, M. Agnelli, G. Giustozzi, M. Tsivgoulis, G. Yaghi, S. Grory, B.M. Furie, K.L. Tadi, P. Zedde, M. Abdul-Rahim, A.H. Dawson, J. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. D’Amore, C. Mosconi, M.G. Bogini, V. Cappellari, M. Rigatelli, A. Bonetti, B. Putaala, J. Tomppo, L. Tatlisumak, T. Bandini, F. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Masotti, L. Grifoni, E. 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. Palaiodimou, L. Mumoli, N. Porta, C. Galati, F. Sacco, S. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Silvestrelli, G. Ciccone, A. Scoditti, U. Denti, L. Mancuso, M. Caselli, M.C. Maccarrone, M. Ulivi, L. Orlandi, G. Giannini, N. Tassinari, T. Lodovici, M.L.D. Rueckert, C. Baldi, A. Toni, D. Gentile, L. Letteri, F. Giuntini, M. Lotti, E.M. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Mannino, M. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Sette, M.D. Schirinzi, E. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Eskandari, A. Vanacker, P. Barlinn, K. Barlinn, J. Deleu, D. Gourbali, V. Caso, V. and Paciaroni, M. Agnelli, G. Giustozzi, M. Tsivgoulis, G. Yaghi, S. Grory, B.M. Furie, K.L. Tadi, P. Zedde, M. Abdul-Rahim, A.H. Dawson, J. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. D’Amore, C. Mosconi, M.G. Bogini, V. Cappellari, M. Rigatelli, A. Bonetti, B. Putaala, J. Tomppo, L. Tatlisumak, T. Bandini, F. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Masotti, L. Grifoni, E. 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. Palaiodimou, L. Mumoli, N. Porta, C. Galati, F. Sacco, S. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Silvestrelli, G. Ciccone, A. Scoditti, U. Denti, L. Mancuso, M. Caselli, M.C. Maccarrone, M. Ulivi, L. Orlandi, G. Giannini, N. Tassinari, T. Lodovici, M.L.D. Rueckert, C. Baldi, A. Toni, D. Gentile, L. Letteri, F. Giuntini, M. Lotti, E.M. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Mannino, M. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Sette, M.D. Schirinzi, E. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Eskandari, A. Vanacker, P. Barlinn, K. Barlinn, J. Deleu, D. Gourbali, V. Caso, V.

Abstract

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. © European Stroke Organisation 2020.

Published
2020

7. Early recurrence in paroxysmal versus sustained atrial fibrillation in patients with acute ischaemic stroke

Author

Paciaroni, M. Angelini, F. Agnelli, G. Tsivgoulis, G. Furie, K.L. Tadi, P. Becattini, C. Falocci, N. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. Altavilla, R. D’Amore, C. Mosconi, M.G. Cimini, L.A. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Bandini, F. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Masotti, L. Vannucchi, V. Sohn, S.-I. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Ntaios, G. Karagkiozi, E. Athanasakis, G. Makaritsis, K. Vadikolias, K. Liantinioti, C. Chondrogianni, M. Mumoli, N. Consoli, D. Galati, F. Sacco, S. Carolei, A. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Silvestrelli, G. Ciccone, A. Scoditti, U. Denti, L. Mancuso, M. Maccarrone, M. Orlandi, G. Giannini, N. Gialdini, G. Tassinari, T. Lodovici, M.L.D. Bono, G. Rueckert, C. Baldi, A. Toni, D. Letteri, F. Giuntini, M. Lotti, E.M. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Sette, M.D. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel Pd-Mer, P. Vanacker, P. Barlinn, K. Pallesen, L.P. Kepplinger, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Gourbali, V. Yaghi, S. Caso, V. and Paciaroni, M. Angelini, F. Agnelli, G. Tsivgoulis, G. Furie, K.L. Tadi, P. Becattini, C. Falocci, N. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. Altavilla, R. D’Amore, C. Mosconi, M.G. Cimini, L.A. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Bandini, F. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Masotti, L. Vannucchi, V. Sohn, S.-I. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Ntaios, G. Karagkiozi, E. Athanasakis, G. Makaritsis, K. Vadikolias, K. Liantinioti, C. Chondrogianni, M. Mumoli, N. Consoli, D. Galati, F. Sacco, S. Carolei, A. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Silvestrelli, G. Ciccone, A. Scoditti, U. Denti, L. Mancuso, M. Maccarrone, M. Orlandi, G. Giannini, N. Gialdini, G. Tassinari, T. Lodovici, M.L.D. Bono, G. Rueckert, C. Baldi, A. Toni, D. Letteri, F. Giuntini, M. Lotti, E.M. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Sette, M.D. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel Pd-Mer, P. Vanacker, P. Barlinn, K. Pallesen, L.P. Kepplinger, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Gourbali, V. Yaghi, S. Caso, V.

Abstract

Background: The relationship between different patterns of atrial fibrillation and early recurrence after an acute ischaemic stroke is unclear. Purpose: In a prospective cohort study, we evaluated the rates of early ischaemic recurrence after an acute ischaemic stroke in patients with paroxysmal atrial fibrillation or sustained atrial fibrillation which included persistent and permanent atrial fibrillation. Methods: In patients with acute ischaemic stroke, atrial fibrillation was categorised as paroxysmal atrial fibrillation or sustained atrial fibrillation. Ischaemic recurrences were the composite of ischaemic stroke, transient ischaemic attack and symptomatic systemic embolism occurring within 90 days from acute index stroke. Results: A total of 2150 patients (1155 females, 53.7%) were enrolled: 930 (43.3%) had paroxysmal atrial fibrillation and 1220 (56.7%) sustained atrial fibrillation. During the 90-day follow-up, 111 ischaemic recurrences were observed in 107 patients: 31 in patients with paroxysmal atrial fibrillation (3.3%) and 76 with sustained atrial fibrillation (6.2%) (hazard ratio (HR) 1.86 (95% CI 1.24–2.81)). Patients with sustained atrial fibrillation were on average older, more likely to have diabetes mellitus, hypertension, history of stroke/ transient ischaemic attack, congestive heart failure, atrial enlargement, high baseline NIHSS-score and implanted pacemaker. After adjustment by Cox proportional hazard model, sustained atrial fibrillation was not associated with early ischaemic recurrences (adjusted HR 1.23 (95% CI 0.74–2.04)). Conclusions: After acute ischaemic stroke, patients with sustained atrial fibrillation had a higher rate of early ischaemic recurrence than patients with paroxysmal atrial fibrillation. After adjustment for relevant risk factors, sustained atrial fibrillation was not associated with a significantly higher risk of recurrence, thus suggesting that the risk profile associated with atrial fibrillation, rather than its patt

Published
2019

8. Causes and Risk Factors of Cerebral Ischemic Events in Patients with Atrial Fibrillation Treated with Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention: The RENo Study

Author

Paciaroni, M. Agnelli, G. Caso, V. Silvestrelli, G. Seiffge, D.J. Engelter, S. De Marchis, G.M. Polymeris, A. Zedde, M.L. Yaghi, S. Michel, P. Eskandari, A. Antonenko, K. Sohn, S.-I. Cappellari, M. Tassinari, T. Tassi, R. Masotti, L. Katsanos, A.H. Giannopoulos, S. Acciarresi, M. Alberti, A. Venti, M. Mosconi, M.G. Vedovati, M.C. Pierini, P. Giustozzi, M. Lotti, E.M. Ntaios, G. Kargiotis, O. Monaco, S. Lochner, P. Bandini, F. Liantinioti, C. Palaiodimou, L. Abdul-Rahim, A.H. Lees, K. Mancuso, M. Pantoni, L. Rosa, S. Bertora, P. Galliazzo, S. Ageno, W. Toso, E. Angelini, F. Chiti, A. Orlandi, G. Denti, L. Flomin, Y. Marcheselli, S. Mumoli, N. Rimoldi, A. Verrengia, E. Schirinzi, E. Del Sette, M. Papamichalis, P. Komnos, A. Popovic, N. Zarkov, M. Rocco, A. Diomedi, M. Giorli, E. Ciccone, A. Grory, B.C.M. Furie, K.L. Bonetti, B. Saia, V. Guideri, F. Acampa, M. Martini, G. Grifoni, E. Padroni, M. Karagkiozi, E. Perlepe, K. Makaritsis, K. Mannino, M. MacCarrone, M. Ulivi, L. Giannini, N. Ferrari, E. Pezzini, A. Doronin, B. Volodina, V. Baldi, A. D'Amore, C. Deleu, D. Corea, F. Putaala, J. Santalucia, P. Nardi, K. Risitano, A. Toni, D. Tsivgoulis, G. and Paciaroni, M. Agnelli, G. Caso, V. Silvestrelli, G. Seiffge, D.J. Engelter, S. De Marchis, G.M. Polymeris, A. Zedde, M.L. Yaghi, S. Michel, P. Eskandari, A. Antonenko, K. Sohn, S.-I. Cappellari, M. Tassinari, T. Tassi, R. Masotti, L. Katsanos, A.H. Giannopoulos, S. Acciarresi, M. Alberti, A. Venti, M. Mosconi, M.G. Vedovati, M.C. Pierini, P. Giustozzi, M. Lotti, E.M. Ntaios, G. Kargiotis, O. Monaco, S. Lochner, P. Bandini, F. Liantinioti, C. Palaiodimou, L. Abdul-Rahim, A.H. Lees, K. Mancuso, M. Pantoni, L. Rosa, S. Bertora, P. Galliazzo, S. Ageno, W. Toso, E. Angelini, F. Chiti, A. Orlandi, G. Denti, L. Flomin, Y. Marcheselli, S. Mumoli, N. Rimoldi, A. Verrengia, E. Schirinzi, E. Del Sette, M. Papamichalis, P. Komnos, A. Popovic, N. Zarkov, M. Rocco, A. Diomedi, M. Giorli, E. Ciccone, A. Grory, B.C.M. Furie, K.L. Bonetti, B. Saia, V. Guideri, F. Acampa, M. Martini, G. Grifoni, E. Padroni, M. Karagkiozi, E. Perlepe, K. Makaritsis, K. Mannino, M. MacCarrone, M. Ulivi, L. Giannini, N. Ferrari, E. Pezzini, A. Doronin, B. Volodina, V. Baldi, A. D'Amore, C. Deleu, D. Corea, F. Putaala, J. Santalucia, P. Nardi, K. Risitano, A. Toni, D. Tsivgoulis, G.

Abstract

Background and Purpose-Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non-Vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention. Methods-Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment. Results-Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio [OR], 3.18; 95% CI, 1.95-5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63-9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83-3.16), and CHA2DS2-VASc score (OR, 1.72 for each point increase; 95% CI, 1.58-1.88) were associated with ischemic events. Among the CHA2DS2-VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33-0.61). Conclusions-In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipid

Published
2019

9. Anticoagulation after Stroke in Patients with Atrial Fibrillation: To Bridge or Not with Low-Molecular-Weight Heparin?

Author

Altavilla, R. Caso, V. Bandini, F. Agnelli, G. Tsivgoulis, G. Yaghi, S. Furie, K.L. Tadi, P. Becattini, C. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. D'Amore, C. Giulia Mosconi, M. Anna Cimini, L. Fusaro, J. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Masotti, L. 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. Chondrogianni, M. Mumoli, N. Consoli, D. Galati, F. Sacco, S. Carolei, A. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Silvestrelli, G. Ciccone, A. Lanari, A. Scoditti, U. Denti, L. Mancuso, M. MacCarrone, M. Ulivi, L. Orlandi, G. Giannini, N. Gialdini, G. Tassinari, T. De Lodovici, M.L. Bono, G. Rueckert, C. Baldi, A. D'Anna, S. Toni, D. Letteri, F. Giuntini, M. Lotti, E.M. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Del Sette, M. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Vanacker, P. Barlinn, K. Pallesen, L.-P. Barlinn, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Gourbali, V. Paciaroni, M. and Altavilla, R. Caso, V. Bandini, F. Agnelli, G. Tsivgoulis, G. Yaghi, S. Furie, K.L. Tadi, P. Becattini, C. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. D'Amore, C. Giulia Mosconi, M. Anna Cimini, L. Fusaro, J. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Masotti, L. 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. Chondrogianni, M. Mumoli, N. Consoli, D. Galati, F. Sacco, S. Carolei, A. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Silvestrelli, G. Ciccone, A. Lanari, A. Scoditti, U. Denti, L. Mancuso, M. MacCarrone, M. Ulivi, L. Orlandi, G. Giannini, N. Gialdini, G. Tassinari, T. De Lodovici, M.L. Bono, G. Rueckert, C. Baldi, A. D'Anna, S. Toni, D. Letteri, F. Giuntini, M. Lotti, E.M. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Del Sette, M. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Vanacker, P. Barlinn, K. Pallesen, L.-P. Barlinn, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Gourbali, V. Paciaroni, M.

Abstract

Background and Purpose-Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods-We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results-Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P<0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions-Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients. © 2019 American Heart Association, Inc.

Published
2019

10. Hemorrhagic transformation in patients with acute ischemic stroke and atrial fibrillation: Time to initiation of oral anticoagulant therapy and outcomes

Author

Paciaroni, M. Bandini, F. Agnelli, G. Tsivgoulis, G. Yaghi, S. Furie, K.L. Tadi, P. Becattini, C. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. D’Amore, C. Mosconi, M.G. Cimini, L.A. Altavilla, R. Volpi, G. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Masotti, L. 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. Chondrogianni, M. Mumoli, N. Consoli, D. Galati, F. Sacco, S. Carolei, A. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Colombo, G. Silvestrelli, G. Ciccone, A. Lanari, A. Scoditti, U. Denti, L. Mancuso, M. Maccarrone, M. Ulivi, L. Orlandi, G. Giannini, N. Gialdini, G. Tassinari, T. De Lodovici, M.L. Bono, G. Rueckert, C. Baldi, A. D'Anna, S. Toni, D. Letteri, F. Giuntini, M. Lotti, E.M. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Del Sette, M. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Vanacker, P. Barlinn, K. Pallesen, L.-P. Barlinn, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Gourbali, V. Caso, V. and Paciaroni, M. Bandini, F. Agnelli, G. Tsivgoulis, G. Yaghi, S. Furie, K.L. Tadi, P. Becattini, C. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. D’Amore, C. Mosconi, M.G. Cimini, L.A. Altavilla, R. Volpi, G. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Masotti, L. 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. Chondrogianni, M. Mumoli, N. Consoli, D. Galati, F. Sacco, S. Carolei, A. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Colombo, G. Silvestrelli, G. Ciccone, A. Lanari, A. Scoditti, U. Denti, L. Mancuso, M. Maccarrone, M. Ulivi, L. Orlandi, G. Giannini, N. Gialdini, G. Tassinari, T. De Lodovici, M.L. Bono, G. Rueckert, C. Baldi, A. D'Anna, S. Toni, D. Letteri, F. Giuntini, M. Lotti, E.M. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Del Sette, M. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Vanacker, P. Barlinn, K. Pallesen, L.-P. Barlinn, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Gourbali, V. Caso, V.

Abstract

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. © 2018 The Authors.

Published
2018

11. Intravenous thrombolysis for acute ischemic stroke associated to extracranial internal carotid artery occlusion: The ICARO-2 study

Author

Paciaroni, M, Agnelli, G, Caso, V, Pieroni, A, Bovi, P, Cappellari, M, Zini, A, Nichelli, P, Inzitari, D, Nesi, M, Nencini, P, Pezzini, A, Padovani, A, Tassinari, T, Orlandi, G, Chiti, A, Gialdini, G, Alberti, A, Venti, M, Acciarresi, M, D'Amore, C, Luda, E, Tassi, R, Martini, G, Ferrarese, C, Beretta, S, Trentini, C, Silvestrelli, G, Lanari, A, Previdi, P, Ciccone, A, Delodovici, M, Bono, G, Galletti, G, Marcheselli, S, Del Sette, M, Traverso, E, Riva, M, Silvestrini, M, Cerqua, R, Consoli, D, Monaco, S, Toni, D, D'amore, C, Toni, D., FERRARESE, CARLO, BERETTA, SIMONE, TRENTINI, CLAUDIA, Paciaroni, M, Agnelli, G, Caso, V, Pieroni, A, Bovi, P, Cappellari, M, Zini, A, Nichelli, P, Inzitari, D, Nesi, M, Nencini, P, Pezzini, A, Padovani, A, Tassinari, T, Orlandi, G, Chiti, A, Gialdini, G, Alberti, A, Venti, M, Acciarresi, M, D'Amore, C, Luda, E, Tassi, R, Martini, G, Ferrarese, C, Beretta, S, Trentini, C, Silvestrelli, G, Lanari, A, Previdi, P, Ciccone, A, Delodovici, M, Bono, G, Galletti, G, Marcheselli, S, Del Sette, M, Traverso, E, Riva, M, Silvestrini, M, Cerqua, R, Consoli, D, Monaco, S, Toni, D, D'amore, C, Toni, D., FERRARESE, CARLO, BERETTA, SIMONE, and TRENTINI, CLAUDIA

Abstract

Background and Purposes: In a case-control study in patients with acute ischemic stroke and extracranial internal carotid artery (eICA) occlusion, thrombolytic treatment was associated with increased mortality. The aim of this cohort study was to assess the efficacy and safety of thrombolysis in patients with eICA occlusion compared to those without eICA occlusion. Methods: Consecutive patients treated with intravenous tissue-type plasminogen activator within 4.5 h from symptom onset included in the Safe Implementation of Thrombolysis in Stroke - International Stroke Thrombolysis Registry (SITS-ISTR) in 20 Italian centres were analyzed. Acute carotid occlusion was diagnosed using ultrasound examination, angio-CT scan or angio-MRI. Since the SITS-ISTR database did not plan to report the site of vessel occlusion, each participating center provided the code of the patient with eICA occlusion. Patients were divided into 2 groups, those with and those without eICA occlusion. Main outcome measures were: death, disability (modified Rankin Scale, mRS, 3-6) and any intracranial bleeding at 3 months. Multiple logistic regression analysis was performed to reveal predictors for main outcomes. The following variables of interest were included in the analysis: presence of eICA occlusion, age, gender, diabetes mellitus, hyperlipidemia, atrial fibrillation, congestive heart failure, previous stroke, current smoking, antiplatelet treatment at stroke onset, baseline NIHSS score, baseline blood glucose, cholesterol and blood pressure, history of hypertension and stroke onset to treatment time. Results: A total of 1,761 patients without eICA occlusion and 137 with eICA occlusion were included in the study. At 3 months, 42 patients were lost to follow-up (3 with eICA occlusion). Death occurred in 30 (22.4%) patients with eICA occlusion and in 175 (10.2%) patients without (p < 0.0001). Death or disability at 3 months occurred in 91 of 134 patients with eICA occlusion (67.9%) compared wit

Published
2012

12. Early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with Non-Vitamin-K oral anticoagulants (RAF-NOACs) Study

Author

Paciaroni, M. Agnelli, G. Falocci, N. Tsivgoulis, G. Vadikolias, K. Liantinioti, C. Chondrogianni, M. Bovi, P. Carletti, M. Cappellari, M. Zedde, M. Ntaios, G. Karagkiozi, E. Athanasakis, G. Makaritsis, K. Silvestrelli, G. Lanari, A. Ciccone, A. Putaala, J. Tomppo, L. Tatlisumak, T. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. D'Amore, C. Becattini, C. Mosconi, M.G. Cimini, L.A. Soloperto, R. Masotti, L. Vannucchi, V. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Sohn, S.-I. Marcheselli, S. Mumoli, N. De Lodovici, M.L. Bono, G. Furie, K.L. Tadi, P. Yaghi, S. Toni, D. Letteri, F. Tassinari, T. Kargiotis, O. Lotti, E.M. Flomin, Y. Mancuso, M. Maccarrone, M. Giannini, N. Bandini, F. Pezzini, A. Poli, L. Padovani, A. Scoditti, U. Denti, L. Consoli, D. Galati, F. Sacco, S. Carolei, A. Tiseo, C. Gourbali, V. Orlandi, G. Giuntini, M. Chiti, A. Giorli, E. Gialdini, G. Corea, F. Ageno, W. Bellesini, M. Colombo, G. Monaco, S. Baronello, M.M. Karapanayiotides, T. Caso, V. and Paciaroni, M. Agnelli, G. Falocci, N. Tsivgoulis, G. Vadikolias, K. Liantinioti, C. Chondrogianni, M. Bovi, P. Carletti, M. Cappellari, M. Zedde, M. Ntaios, G. Karagkiozi, E. Athanasakis, G. Makaritsis, K. Silvestrelli, G. Lanari, A. Ciccone, A. Putaala, J. Tomppo, L. Tatlisumak, T. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. D'Amore, C. Becattini, C. Mosconi, M.G. Cimini, L.A. Soloperto, R. Masotti, L. Vannucchi, V. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Sohn, S.-I. Marcheselli, S. Mumoli, N. De Lodovici, M.L. Bono, G. Furie, K.L. Tadi, P. Yaghi, S. Toni, D. Letteri, F. Tassinari, T. Kargiotis, O. Lotti, E.M. Flomin, Y. Mancuso, M. Maccarrone, M. Giannini, N. Bandini, F. Pezzini, A. Poli, L. Padovani, A. Scoditti, U. Denti, L. Consoli, D. Galati, F. Sacco, S. Carolei, A. Tiseo, C. Gourbali, V. Orlandi, G. Giuntini, M. Chiti, A. Giorli, E. Gialdini, G. Corea, F. Ageno, W. Bellesini, M. Colombo, G. Monaco, S. Baronello, M.M. Karapanayiotides, T. Caso, V.

Abstract

Background--The optimal timing to administer non-vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within90 days)and their timing in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention. Methods and Results--Recurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA2DS2-VASc score > 4 and less reduced renal function. Thirty-two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated > 14 days after acute stroke. Conclusions--In patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days. © 2017 The Authors.

Published
2017

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

Author

Acciarresi, M. Paciaroni, M. Agnelli, G. Falocci, N. Caso, V. Becattini, C. Marcheselli, S. Rueckert, C. Pezzini, A. Morotti, A. Costa, P. Padovani, A. Csiba, L. Szabó, L. Sohn, S.-I. Tassinari, T. Abdul-Rahim, A.H. Michel, P. Cordier, M. Vanacker, P. Remillard, S. Alberti, A. Venti, M. D'Amore, C. Scoditti, U. Denti, L. Orlandi, G. Chiti, A. Gialdini, G. Bovi, P. Carletti, M. Rigatelli, A. Putaala, J. Tatlisumak, T. Masotti, L. Lorenzini, G. Tassi, R. Guideri, F. Martini, G. Tsivgoulis, G. Vadikolias, K. Liantinioti, C. Corea, F. Del Sette, M. Ageno, W. De Lodovici, M.L. Bono, G. Baldi, A. D'Anna, S. Sacco, S. Carolei, A. Tiseo, C. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Consoli, D. Galati, F. Pieroni, A. Toni, D. Monaco, S. Baronello, M.M. Barlinn, K. Pallesen, L.-P. Kepplinger, J. Bodechtel, U. Gerber, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Mosconi, M.G. Lees, K.R. and Acciarresi, M. Paciaroni, M. Agnelli, G. Falocci, N. Caso, V. Becattini, C. Marcheselli, S. Rueckert, C. Pezzini, A. Morotti, A. Costa, P. Padovani, A. Csiba, L. Szabó, L. Sohn, S.-I. Tassinari, T. Abdul-Rahim, A.H. Michel, P. Cordier, M. Vanacker, P. Remillard, S. Alberti, A. Venti, M. D'Amore, C. Scoditti, U. Denti, L. Orlandi, G. Chiti, A. Gialdini, G. Bovi, P. Carletti, M. Rigatelli, A. Putaala, J. Tatlisumak, T. Masotti, L. Lorenzini, G. Tassi, R. Guideri, F. Martini, G. Tsivgoulis, G. Vadikolias, K. Liantinioti, C. Corea, F. Del Sette, M. Ageno, W. De Lodovici, M.L. Bono, G. Baldi, A. D'Anna, S. Sacco, S. Carolei, A. Tiseo, C. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Consoli, D. Galati, F. Pieroni, A. Toni, D. Monaco, S. Baronello, M.M. Barlinn, K. Pallesen, L.-P. Kepplinger, J. Bodechtel, U. Gerber, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Mosconi, M.G. Lees, K.R.

Abstract

Background and Purpose 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). Methods 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. Results 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. Conclusions 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. © 2017 National Stroke Association

Published
2017

14. 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)

Author

Antonenko, K. Paciaroni, M. Agnelli, G. Falocci, N. Becattini, C. Marcheselli, S. Rueckert, C. Pezzini, A. Poli, L. Padovani, A. Csiba, L. Szabó, L. Sohn, S.-I. Tassinari, T. Abdul-Rahim, A.H. Michel, P. Cordier, M. Vanacker, P. Remillard, S. Alberti, A. Venti, M. Acciarresi, M. D’Amore, C. Scoditti, U. Denti, L. Orlandi, G. Chiti, A. Gialdini, G. Bovi, P. Carletti, M. Rigatelli, A. Putaala, J. Tatlisumak, T. Masotti, L. Lorenzini, G. Tassi, R. Guideri, F. Martini, G. Tsivgoulis, G. Vadikolias, K. Papageorgiou, S.G. Corea, F. Sette, M.D. Ageno, W. Lodovici, M.L.D. Bono, G. Baldi, A. D’Anna, S. Sacco, S. Carolei, A. Tiseo, C. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Consoli, D. Galati, F. Pieroni, A. Toni, D. Monaco, S. Baronello, M.M. Barlinn, K. Pallesen, L.-P. Kepplinger, J. Bodechtel, U. Gerber, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Mosconi, M.G. Lees, K.R. Caso, V. and Antonenko, K. Paciaroni, M. Agnelli, G. Falocci, N. Becattini, C. Marcheselli, S. Rueckert, C. Pezzini, A. Poli, L. Padovani, A. Csiba, L. Szabó, L. Sohn, S.-I. Tassinari, T. Abdul-Rahim, A.H. Michel, P. Cordier, M. Vanacker, P. Remillard, S. Alberti, A. Venti, M. Acciarresi, M. D’Amore, C. Scoditti, U. Denti, L. Orlandi, G. Chiti, A. Gialdini, G. Bovi, P. Carletti, M. Rigatelli, A. Putaala, J. Tatlisumak, T. Masotti, L. Lorenzini, G. Tassi, R. Guideri, F. Martini, G. Tsivgoulis, G. Vadikolias, K. Papageorgiou, S.G. Corea, F. Sette, M.D. Ageno, W. Lodovici, M.L.D. Bono, G. Baldi, A. D’Anna, S. Sacco, S. Carolei, A. Tiseo, C. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Consoli, D. Galati, F. Pieroni, A. Toni, D. Monaco, S. Baronello, M.M. Barlinn, K. Pallesen, L.-P. Kepplinger, J. Bodechtel, U. Gerber, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Mosconi, M.G. Lees, K.R. Caso, V.

Abstract

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 stu

Published
2017

15. Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients with Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study

Author

Paciaroni, M. Agnelli, G. Caso, V. Tsivgoulis, G. Furie, K.L. Tadi, P. Becattini, C. Falocci, N. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. D'Amore, C. Mosconi, M.G. Cimini, L.A. Procopio, A. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Bandini, F. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Masotti, L. Vannucchi, V. Sohn, S.-I. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Ntaios, G. Karagkiozi, E. Athanasakis, G. Makaritsis, K. Vadikolias, K. Liantinioti, C. Chondrogianni, M. Mumoli, N. Consoli, D. Galati, F. Sacco, S. Carolei, A. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Colombo, G. Silvestrelli, G. Ciccone, A. Scoditti, U. Denti, L. Mancuso, M. Maccarrone, M. Orlandi, G. Giannini, N. Gialdini, G. Tassinari, T. De Lodovici, M.L. Bono, G. Rueckert, C. Baldi, A. D'Anna, S. Toni, D. Letteri, F. Giuntini, M. Lotti, E.M. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Del Sette, M. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Vanacker, P. Barlinn, K. Pallesen, L.-P. Kepplinger, J. Bodechtel, U. Gerber, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Gourbali, V. Yaghi, S. and Paciaroni, M. Agnelli, G. Caso, V. Tsivgoulis, G. Furie, K.L. Tadi, P. Becattini, C. Falocci, N. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. D'Amore, C. Mosconi, M.G. Cimini, L.A. Procopio, A. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Bandini, F. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Masotti, L. Vannucchi, V. Sohn, S.-I. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Ntaios, G. Karagkiozi, E. Athanasakis, G. Makaritsis, K. Vadikolias, K. Liantinioti, C. Chondrogianni, M. Mumoli, N. Consoli, D. Galati, F. Sacco, S. Carolei, A. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Colombo, G. Silvestrelli, G. Ciccone, A. Scoditti, U. Denti, L. Mancuso, M. Maccarrone, M. Orlandi, G. Giannini, N. Gialdini, G. Tassinari, T. De Lodovici, M.L. Bono, G. Rueckert, C. Baldi, A. D'Anna, S. Toni, D. Letteri, F. Giuntini, M. Lotti, E.M. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Del Sette, M. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Vanacker, P. Barlinn, K. Pallesen, L.-P. Kepplinger, J. Bodechtel, U. Gerber, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Gourbali, V. Yaghi, S.

Abstract

Background and Purposes - This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods - The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P=0.10) for major bleedings. Results - The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P=0.009) for ischemic outcome events and 0.407 (0.275-0.540; P=0.14) for hemorrhagic outcome events. Conclusions - In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings. © 2017 American Heart Association, Inc.

Published
2017

16. Prognostic value of trans-thoracic echocardiography in patients with acute stroke and atrial fibrillation: findings from the RAF study

Author

Paciaroni, M. Agnelli, G. Falocci, N. Caso, V. Becattini, C. Marcheselli, S. Rueckert, C. Pezzini, A. Poli, L. Padovani, A. Csiba, L. Szabó, L. Sohn, S.-I. Tassinari, T. Abdul-Rahim, A.H. Michel, P. Cordier, M. Vanacker, P. Remillard, S. Alberti, A. Venti, M. Acciarresi, M. D’Amore, C. Mosconi, M.G. Scoditti, U. Denti, L. Orlandi, G. Chiti, A. Gialdini, G. Bovi, P. Carletti, M. Rigatelli, A. Putaala, J. Tatlisumak, T. Masotti, L. Lorenzini, G. Tassi, R. Guideri, F. Martini, G. Tsivgoulis, G. Vadikolias, K. Liantinioti, C. Corea, F. Del Sette, M. Ageno, W. De Lodovici, M.L. Bono, G. Baldi, A. D’Anna, S. Sacco, S. Carolei, A. Tiseo, C. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Consoli, D. Galati, F. Pieroni, A. Toni, D. Monaco, S. Baronello, M.M. Barlinn, K. Pallesen, L.-P. Kepplinger, J. Bodechtel, U. Gerber, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Lees, K.R. and Paciaroni, M. Agnelli, G. Falocci, N. Caso, V. Becattini, C. Marcheselli, S. Rueckert, C. Pezzini, A. Poli, L. Padovani, A. Csiba, L. Szabó, L. Sohn, S.-I. Tassinari, T. Abdul-Rahim, A.H. Michel, P. Cordier, M. Vanacker, P. Remillard, S. Alberti, A. Venti, M. Acciarresi, M. D’Amore, C. Mosconi, M.G. Scoditti, U. Denti, L. Orlandi, G. Chiti, A. Gialdini, G. Bovi, P. Carletti, M. Rigatelli, A. Putaala, J. Tatlisumak, T. Masotti, L. Lorenzini, G. Tassi, R. Guideri, F. Martini, G. Tsivgoulis, G. Vadikolias, K. Liantinioti, C. Corea, F. Del Sette, M. Ageno, W. De Lodovici, M.L. Bono, G. Baldi, A. D’Anna, S. Sacco, S. Carolei, A. Tiseo, C. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Consoli, D. Galati, F. Pieroni, A. Toni, D. Monaco, S. Baronello, M.M. Barlinn, K. Pallesen, L.-P. Kepplinger, J. Bodechtel, U. Gerber, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Lees, K.R.

Abstract

Anticoagulant therapy is recommended for the secondary prevention of stroke in patients with atrial fibrillation (AF). The identification of patients at high risk for early recurrence, which are potential candidates to prompt anticoagulation, is crucial to justify the risk of bleeding associated with early anticoagulant treatment. The aim of this study was to evaluate in patients with acute ischemic stroke and AF the association between findings at trans-thoracic echocardiography (TTE) and 90 days recurrence. In consecutive patients with acute ischemic stroke and AF, TTE was performed within 7 days from hospital admission. Study outcomes were recurrent ischemic cerebrovascular events (stroke or TIA) and systemic embolism. 854 patients (mean age 76.3 ± 9.5 years) underwent a TTE evaluation; 63 patients (7.4 %) had at least a study outcome event. Left atrial thrombosis was present in 11 patients (1.3 %) among whom 1 had recurrent ischemic event. Left atrial enlargement was present in 548 patients (64.2 %) among whom 51 (9.3 %) had recurrent ischemic events. The recurrence rate in the 197 patients with severe left atrial enlargement was 11.7 %. On multivariate analysis, the presence of atrial enlargement (OR 2.13; 95 % CI 1.06–4.29, p = 0.033) and CHA2DS2-VASc score (OR 1.22; 95 % CI 1.04–1.45, p = 0.018, for each point increase) were correlated with ischemic recurrences. In patients with AF-associated acute stroke, left atrial enlargement is an independent marker of recurrent stroke and systemic embolism. The risk of recurrence is accounted for by severe atrial enlargement. TTE-detected left atrial thrombosis is relatively uncommon. © 2015, Springer-Verlag Berlin Heidelberg.

Published
2016

17. Early recurrence and cerebral bleeding in patients with acute ischemic stroke and atrial fibrillation: Effect of anticoagulation and its timing: The RAF study

Author

Paciaroni, M. Agnelli, G. Falocci, N. Caso, V. Becattini, C. Marcheselli, S. Rueckert, C. Pezzini, A. Poli, L. Padovani, A. Csiba, L. Szabó, L. Sohn, S.-I. Tassinari, T. Abdul-Rahim, A.H. Michel, P. Cordier, M. Vanacker, P. Remillard, S. Alberti, A. Venti, M. Scoditti, U. Denti, L. Orlandi, G. Chiti, A. Gialdini, G. Bovi, P. Carletti, M. Rigatelli, A. Putaala, J. Tatlisumak, T. Masotti, L. Lorenzini, G. Tassi, R. Guideri, F. Martini, G. Tsivgoulis, G. Vadikolias, K. Liantinioti, C. Corea, F. Del Sette, M. Ageno, W. De Lodovici, M.L. Bono, G. Baldi, A. D'Anna, S. Sacco, S. Carolei, A. Tiseo, C. Acciarresi, M. D'Amore, C. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Consoli, D. Galati, F. Pieroni, A. Toni, D. Monaco, S. Baronello, M.M. Barlinn, K. Pallesen, L.-P. Kepplinger, J. Bodechtel, U. Gerber, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Mosconi, M.G. Bubba, V. Silvestri, I. Lees, K.R. and Paciaroni, M. Agnelli, G. Falocci, N. Caso, V. Becattini, C. Marcheselli, S. Rueckert, C. Pezzini, A. Poli, L. Padovani, A. Csiba, L. Szabó, L. Sohn, S.-I. Tassinari, T. Abdul-Rahim, A.H. Michel, P. Cordier, M. Vanacker, P. Remillard, S. Alberti, A. Venti, M. Scoditti, U. Denti, L. Orlandi, G. Chiti, A. Gialdini, G. Bovi, P. Carletti, M. Rigatelli, A. Putaala, J. Tatlisumak, T. Masotti, L. Lorenzini, G. Tassi, R. Guideri, F. Martini, G. Tsivgoulis, G. Vadikolias, K. Liantinioti, C. Corea, F. Del Sette, M. Ageno, W. De Lodovici, M.L. Bono, G. Baldi, A. D'Anna, S. Sacco, S. Carolei, A. Tiseo, C. Acciarresi, M. D'Amore, C. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Consoli, D. Galati, F. Pieroni, A. Toni, D. Monaco, S. Baronello, M.M. Barlinn, K. Pallesen, L.-P. Kepplinger, J. Bodechtel, U. Gerber, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Mosconi, M.G. Bubba, V. Silvestri, I. Lees, K.R.

Abstract

Background and Purpose - 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. Methods - The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results - Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Conclusions - Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large isc

Published
2015

18. Intravenous thrombolysis or endovascular therapy for acute ischemic stroke associated with cervical internal carotid artery occlusion: the ICARO-3 study

Author

Paciaroni, M. Inzitari, D. Agnelli, G. Caso, V. Balucani, C. Grotta, J.C. Sarraj, A. Sung-Il, S. Chamorro, A. Urra, X. Leys, D. Henon, H. Cordonnier, C. Dequatre, N. Aguettaz, P. Alberti, A. Venti, M. Acciarresi, M. D’Amore, C. Zini, A. Vallone, S. Dell’Acqua, M.L. Menetti, F. Nencini, P. Mangiafico, S. Barlinn, K. Kepplinger, J. Bodechtel, U. Gerber, J. Bovi, P. Cappellari, M. Linfante, I. Dabus, G. Marcheselli, S. Pezzini, A. Padovani, A. Alexandrov, A.V. Shahripour, R.B. Sessa, M. Giacalone, G. Silvestrelli, G. Lanari, A. Ciccone, A. De Vito, A. Azzini, C. Saletti, A. Fainardi, E. Orlandi, G. Chiti, A. Gialdini, G. Silvestrini, M. Ferrarese, C. Beretta, S. Tassi, R. Martini, G. Tsivgoulis, G. Vasdekis, S.N. Consoli, D. Baldi, A. D’Anna, S. Luda, E. Varbella, F. Galletti, G. Invernizzi, P. Donati, E. De Lodovici, M.L. Bono, G. Corea, F. Sette, M.D. Monaco, S. Riva, M. Tassinari, T. Scoditti, U. Toni, D. and Paciaroni, M. Inzitari, D. Agnelli, G. Caso, V. Balucani, C. Grotta, J.C. Sarraj, A. Sung-Il, S. Chamorro, A. Urra, X. Leys, D. Henon, H. Cordonnier, C. Dequatre, N. Aguettaz, P. Alberti, A. Venti, M. Acciarresi, M. D’Amore, C. Zini, A. Vallone, S. Dell’Acqua, M.L. Menetti, F. Nencini, P. Mangiafico, S. Barlinn, K. Kepplinger, J. Bodechtel, U. Gerber, J. Bovi, P. Cappellari, M. Linfante, I. Dabus, G. Marcheselli, S. Pezzini, A. Padovani, A. Alexandrov, A.V. Shahripour, R.B. Sessa, M. Giacalone, G. Silvestrelli, G. Lanari, A. Ciccone, A. De Vito, A. Azzini, C. Saletti, A. Fainardi, E. Orlandi, G. Chiti, A. Gialdini, G. Silvestrini, M. Ferrarese, C. Beretta, S. Tassi, R. Martini, G. Tsivgoulis, G. Vasdekis, S.N. Consoli, D. Baldi, A. D’Anna, S. Luda, E. Varbella, F. Galletti, G. Invernizzi, P. Donati, E. De Lodovici, M.L. Bono, G. Corea, F. Sette, M.D. Monaco, S. Riva, M. Tassinari, T. Scoditti, U. Toni, D.

Abstract

The aim of the ICARO-3 study was to evaluate whether intra-arterial treatment, compared to intravenous thrombolysis, increases the rate of favourable functional outcome at 3 months in acute ischemic stroke and extracranial ICA occlusion. ICARO-3 was a non-randomized therapeutic trial that performed a non-blind assessment of outcomes using retrospective data collected prospectively from 37 centres in 7 countries. Patients treated with endovascular treatment within 6 h from stroke onset (cases) were matched with patients treated with intravenous thrombolysis within 4.5 h from symptom onset (controls). Patients receiving either intravenous or endovascular therapy were included among the cases. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale (mRS), dichotomized as favourable (score of 0–2) or unfavourable (score of 3–6). Safety outcomes were death and any intracranial bleeding. Included in the analysis were 324 cases and 324 controls: 105 cases (32.4 %) had a favourable outcome as compared with 89 controls (27.4 %) [adjusted odds ratio (OR) 1.25, 95 % confidence interval (CI) 0.88–1.79, p = 0.1]. In the adjusted analysis, treatment with intra-arterial procedures was significantly associated with a reduction of mortality (OR 0.61, 95 % CI 0.40–0.93, p = 0.022). The rates of patients with severe disability or death (mRS 5–6) were similar in cases and controls (30.5 versus 32.4 %, p = 0.67). For the ordinal analysis, adjusted for age, sex, NIHSS, presence of diabetes mellitus and atrial fibrillation, the common odds ratio was 1.15 (95 % IC 0.86–1.54), p = 0.33. There were more cases of intracranial bleeding (37.0 versus 17.3 %, p = 0.0001) in the intra-arterial procedure group than in the intravenous group. After the exclusion of the 135 cases treated with the combination of I.V. thrombolysis and I.A. procedures, 67/189 of those treated with I.A. procedures (35.3 %) had a favourable outcome, compared to 89/324 of those treated with I.V.

Published
2015

19. Intravenous thrombolysis or endovascular therapy for acute ischemic stroke associated with cervical internal carotid artery occlusion: the ICARO-3 study

Author

Paciaroni, M, Inzitari, D, Agnelli, G, Caso, V, Balucani, C, Grotta, J, Sarraj, A, Sung Il, S, Chamorro, A, Urra, X, Leys, D, Henon, H, Cordonnier, C, Dequatre, N, Aguettaz, P, Alberti, A, Venti, M, Acciarresi, M, D'Amore, C, Zini, A, Vallone, S, Dell'Acqua, M, Menetti, F, Nencini, P, Mangiafico, S, Barlinn, K, Kepplinger, J, Bodechtel, U, Gerber, J, Bovi, P, Cappellari, M, Linfante, I, Dabus, G, Marcheselli, S, Pezzini, A, Padovani, A, Alexandrov, A, Shahripour, R, Sessa, M, Giacalone, G, Silvestrelli, G, Lanari, A, Ciccone, A, De Vito, A, Azzini, C, Saletti, A, Fainardi, E, Orlandi, G, Chiti, A, Gialdini, G, Silvestrini, M, Ferrarese, C, Beretta, S, Tassi, R, Martini, G, Tsivgoulis, G, Vasdekis, S, Consoli, D, Baldi, A, D'Anna, S, Luda, E, Varbella, F, Galletti, G, Invernizzi, P, Donati, E, De Lodovici, M, Bono, G, Corea, F, Sette, M, Monaco, S, Riva, M, Tassinari, T, Scoditti, U, Toni, D, FERRARESE, CARLO, RIVA, MARTA, Toni, D., Paciaroni, M, Inzitari, D, Agnelli, G, Caso, V, Balucani, C, Grotta, J, Sarraj, A, Sung Il, S, Chamorro, A, Urra, X, Leys, D, Henon, H, Cordonnier, C, Dequatre, N, Aguettaz, P, Alberti, A, Venti, M, Acciarresi, M, D'Amore, C, Zini, A, Vallone, S, Dell'Acqua, M, Menetti, F, Nencini, P, Mangiafico, S, Barlinn, K, Kepplinger, J, Bodechtel, U, Gerber, J, Bovi, P, Cappellari, M, Linfante, I, Dabus, G, Marcheselli, S, Pezzini, A, Padovani, A, Alexandrov, A, Shahripour, R, Sessa, M, Giacalone, G, Silvestrelli, G, Lanari, A, Ciccone, A, De Vito, A, Azzini, C, Saletti, A, Fainardi, E, Orlandi, G, Chiti, A, Gialdini, G, Silvestrini, M, Ferrarese, C, Beretta, S, Tassi, R, Martini, G, Tsivgoulis, G, Vasdekis, S, Consoli, D, Baldi, A, D'Anna, S, Luda, E, Varbella, F, Galletti, G, Invernizzi, P, Donati, E, De Lodovici, M, Bono, G, Corea, F, Sette, M, Monaco, S, Riva, M, Tassinari, T, Scoditti, U, Toni, D, FERRARESE, CARLO, RIVA, MARTA, and Toni, D.

Abstract

The aim of the ICARO-3 study was to evaluate whether intra-arterial treatment, compared to intravenous thrombolysis, increases the rate of favourable functional outcome at 3 months in acute ischemic stroke and extracranial ICA occlusion. ICARO-3 was a non-randomized therapeutic trial that performed a non-blind assessment of outcomes using retrospective data collected prospectively from 37 centres in 7 countries. Patients treated with endovascular treatment within 6 h from stroke onset (cases) were matched with patients treated with intravenous thrombolysis within 4.5 h from symptom onset (controls). Patients receiving either intravenous or endovascular therapy were included among the cases. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale (mRS), dichotomized as favourable (score of 0–2) or unfavourable (score of 3–6). Safety outcomes were death and any intracranial bleeding. Included in the analysis were 324 cases and 324 controls: 105 cases (32.4 %) had a favourable outcome as compared with 89 controls (27.4 %) [adjusted odds ratio (OR) 1.25, 95 % confidence interval (CI) 0.88–1.79, p = 0.1]. In the adjusted analysis, treatment with intra-arterial procedures was significantly associated with a reduction of mortality (OR 0.61, 95 % CI 0.40–0.93, p = 0.022). The rates of patients with severe disability or death (mRS 5–6) were similar in cases and controls (30.5 versus 32.4 %, p = 0.67). For the ordinal analysis, adjusted for age, sex, NIHSS, presence of diabetes mellitus and atrial fibrillation, the common odds ratio was 1.15 (95 % IC 0.86–1.54), p = 0.33. There were more cases of intracranial bleeding (37.0 versus 17.3 %, p = 0.0001) in the intra-arterial procedure group than in the intravenous group. After the exclusion of the 135 cases treated with the combination of I.V. thrombolysis and I.A. procedures, 67/189 of those trea

Published
2015

20. Systemic thrombolysis in patients with acute ischemic stroke and Internal Carotid ARtery Occlusion: the ICARO study

Author

Paciaroni, M, Balucani, C, Agnelli, G, Caso, V, Silvestrelli, G, Grotta, J, Demchuk, A, Sohn, S, Orlandi, G, Leys, D, Pezzini, A, Alexandrov, A, Silvestrini, M, Fofi, L, Barlinn, K, Inzitari, D, Ferrarese, C, Tassi, R, Tsivgoulis, G, Consoli, D, Baldi, A, Bovi, P, Luda, E, Galletti, G, Invernizzi, P, Delodovici, M, Corea, F, Del Sette, M, Monaco, S, Marcheselli, S, Alberti, A, Venti, M, Acciarresi, M, D'Amore, C, Macellari, F, Lanari, A, Previdi, P, Gonzales, N, Pandurengan, R, Vahidy, F, Sline, M, Bal, S, Chiti, A, Gialdini, G, Dumont, F, Cordonnier, C, Debette, S, Padovani, A, Cerqua, R, Bodechtel, U, Kepplinger, J, Nesi, M, Nencini, P, Beretta, S, Trentini, C, Martini, G, Piperidou, C, Heliopoulos, I, D'Anna, S, Cappellari, M, Donati, E, Bono, G, Traverso, E, Toni, D, FERRARESE, CARLO, INVERNIZZI, PAOLA, DeLodovici, M, BERETTA, SIMONE, TRENTINI, CLAUDIA, Toni, D., Paciaroni, M, Balucani, C, Agnelli, G, Caso, V, Silvestrelli, G, Grotta, J, Demchuk, A, Sohn, S, Orlandi, G, Leys, D, Pezzini, A, Alexandrov, A, Silvestrini, M, Fofi, L, Barlinn, K, Inzitari, D, Ferrarese, C, Tassi, R, Tsivgoulis, G, Consoli, D, Baldi, A, Bovi, P, Luda, E, Galletti, G, Invernizzi, P, Delodovici, M, Corea, F, Del Sette, M, Monaco, S, Marcheselli, S, Alberti, A, Venti, M, Acciarresi, M, D'Amore, C, Macellari, F, Lanari, A, Previdi, P, Gonzales, N, Pandurengan, R, Vahidy, F, Sline, M, Bal, S, Chiti, A, Gialdini, G, Dumont, F, Cordonnier, C, Debette, S, Padovani, A, Cerqua, R, Bodechtel, U, Kepplinger, J, Nesi, M, Nencini, P, Beretta, S, Trentini, C, Martini, G, Piperidou, C, Heliopoulos, I, D'Anna, S, Cappellari, M, Donati, E, Bono, G, Traverso, E, Toni, D, FERRARESE, CARLO, INVERNIZZI, PAOLA, DeLodovici, M, BERETTA, SIMONE, TRENTINI, CLAUDIA, and Toni, D.

Abstract

Background and Purpose-: The beneficial effect of intravenous thrombolytic therapy in patients with acute ischemic stroke attributable to internal carotid artery (ICA) occlusion remains unclear. The aim of this study was to evaluate the efficacy and safety of intravenous recombinant tissue-type plasminogen activator in these patients. Methods-: ICARO was a case-control multicenter study on prospectively collected data. Patients with acute ischemic stroke and ICA occlusion treated with intravenous recombinant tissue-type plasminogen activator within 4.5 hours from symptom onset (cases) were compared to matched patients with acute stroke and ICA occlusion not treated with recombinant tissue-type plasminogen activator (controls). Cases and controls were matched for age, gender, and stroke severity. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale, dichotomized as favorable (score of 0-2) or unfavorable (score of 3-6). Safety outcomes were death and any intracranial bleeding. Results-: Included in the analysis were 253 cases and 253 controls. Seventy-three cases (28.9%) had a favorable outcome as compared with 52 controls (20.6%; adjusted odds ratio (OR), 1.80; 95% confidence interval [CI], 1.03-3.15; P=0.037). A total of 104 patients died, 65 cases (25.7%) and 39 controls (15.4%; adjusted OR, 2.28; 95% CI, 1.36-3.22; P=0.001). There were more fatal bleedings (2.8% versus 0.4%; OR, 7.17; 95% CI, 0.87-58.71; P=0.068) in the cases than in the controls. Conclusions-: In patients with stroke attributable to ICA occlusion, thrombolytic therapy Results in a significant reduction in the proportion of patients dependent in activities of daily living. Increases in death and any intracranial bleeding were the trade-offs for this clinical benefit.

Published
2012

21. 4G/5G PAI-1 promoter polymorphism and acute-phase levels of PAI-1 following coronary bypass surgery: A prospective study

Author

Burzotta, Francesco, Iacoviello, Licia, Di Castelnuovo, Augusto Filippo, Zamparelli, Roberto, D'Orazio, Alessia, Amore, C., Schiavello, R., Donati, M. B., Maseri, A., Possati, G., Andreotti, Felicita, Burzotta F. (ORCID:0000-0002-6569-9401), Iacoviello L., Di Castelnuovo A., Zamparelli R. (ORCID:0000-0002-3085-7529), D'Orazio A., Andreotti F. (ORCID:0000-0002-1456-6430), Burzotta, Francesco, Iacoviello, Licia, Di Castelnuovo, Augusto Filippo, Zamparelli, Roberto, D'Orazio, Alessia, Amore, C., Schiavello, R., Donati, M. B., Maseri, A., Possati, G., Andreotti, Felicita, Burzotta F. (ORCID:0000-0002-6569-9401), Iacoviello L., Di Castelnuovo A., Zamparelli R. (ORCID:0000-0002-3085-7529), D'Orazio A., and Andreotti F. (ORCID:0000-0002-1456-6430)

Abstract

Background and objective: The 4G/5G plasminogen activator inhibitor-1 (PAI-1) promoter polymorphism has been associated with basal PAI-1 levels, with ischemic heart disease, and with adverse prognosis in critically ill patients. We hypothesized it might also influence the acute-phase levels of PAI-1 following coronary bypass surgery. Methods: In 111 consecutive patients undergoing elective coronary bypass surgery, 4G/5G genotyping and serial plasma PAI-1 activity and antigen levels were prospectively measured before surgery, daily up to 72 h, and at discharge. The inflammatory reaction was additionally assessed by white cell count, fibrinogen, interleukin-6, and C-reactive protein levels. Results: PAI-1 activity and antigen concentrations increased approximately two-fold after surgery, peaking at 48 hours. Carriers of the 4G-allele, compared with 5G/5G homozygotes, showed approximately 20% higher PAI-1 activity and antigen both preoperatively (P = 0.007 and P = 0.035) and after surgery. White cell count, fibrinogen, interleukin-6, and C-reactive protein values did not differ significantly according to genotypic groups. In multivariate analysis, the 4G/5G genotype was the only significant modulator of postoperative PAI-1 activity (P = 0.003) and the main significant modulator of postoperative PAI-1 antigen (P = 0.013). No significant interaction was found between the effects of time and genotype on postoperative PAI-1. This indicates that the association between 4G/5G and acute-phase PAI-1 levels is secondary to the genotype-related difference of baseline PAI-1. Conclusions: Postoperative PAI-1 concentrations of patients undergoing elective coronary bypass surgery are higher in carriers of the 4G-allele than in 5G/5G homozygotes as a result of higher baseline values. Knowledge of 4G/5G status may be useful to predict acute-phase PAI-1 concentrations. © 2004 Kluwer Academic Publishers.

Published
2003

23. [The role of 4G/5G polymorphism in the regulation of plasma levels of PAI-1: a model of interaction between genetic and environmental factors]

Author

Burzotta, Francesco, Di Castelnuovo, Augusto Filippo, Amore, C, D'Orazio, Alessia, Donati, M B, Iacoviello, Licia, Burzotta, F (ORCID:0000-0002-6569-9401), Di Castelnuovo, A, D'Orazio, A, Iacoviello, L, Burzotta, Francesco, Di Castelnuovo, Augusto Filippo, Amore, C, D'Orazio, Alessia, Donati, M B, Iacoviello, Licia, Burzotta, F (ORCID:0000-0002-6569-9401), Di Castelnuovo, A, D'Orazio, A, and Iacoviello, L

Abstract

N/A

Published
1998

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