Browsing by Author "Tsivgoulis, Georgios"
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Item Global Impact of COVID-19 on Stroke Care and IV Thrombolysis(2021) Nogueira, Raúl G.; Qureshi, Muhammad M.; Abdalkader, Mohamad; Martins, Sheila Ouriques; Yamagami, Hiroshi; Mansour, Ossama Yassin; Qiu, Zhongming; Sathya, Anvitha; Czlonkowska, Anna; Tsivgoulis, Georgios; Aguiar de Sousa, Diana; Demeestere, Jelle; Mikulik, Robert; Vanacker, Peter; Siegler, James E.; Kõrv, Janika; Biller, Jose; Liang, Conrad W.; Sangha, Navdeep S.; Zha, Alicia M.; Czap, Alexandra L.; Holmstedt, Christine Anne; Turan, Tanya N.; Ntaios, George; Malhotra, Konark; Tayal, Ashis; Loochtan, Aaron; Ranta, Annamarei; Mistry, Eva A.; Alexandrov, Anne W.; Huang, David Y.; Yaghi, Shadi; Raz, Eytan; Sheth, Sunil A.; Mohammaden, Mahmoud H.; Frankel, Michael; Bila Lamou, Eric Guemekane; Aref, Hany M.; Elbassiouny, Ahmed; Hassan, Farouk; Menecie, Tarek; Mustafa, Wessam; Shokr, Hossam M.; Roushdy, Tamer; Sarfo, Fred S.; Alabi, Tolulope Oyetunde; Arabambi, Babawale; Nwazor, Ernest O.; Sunmonu, Taofiki Ajao; Wahab, Kolawole; Yaria, Joseph; Hussein Mohammed, Haytham; Adebayo, Philip B.; Riahi, Anis D.; Sassi, Samia Ben; Navia, Víctor; Olavarría, VerónicaObjective To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. Methods We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. Results There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] −11.7 to −11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI −13.8 to −12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI −13.7 to −10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2–9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. Conclusions The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.Publication Safety and efficacy of factor XIa inhibition with milvexian for secondary stroke prevention (AXIOMATIC-SSP): a phase 2, international, randomised, double-blind, placebo-controlled, dose-finding trial(2024) Sharma, Mukul; Molina, Carlos; Toyoda, Kazunori; Bereczki, Daniel; Bangdiwala, Shrikant; Kasner, Scott; Lutsep, Helmi; Tsivgoulis, Georgios; Ntaios, George; Czlonkowska, Anna; Shuaib, Ashfaq; Amarenco, Pierre; Endres, Matthias; Yoon, Byung-Woo; Tanne, David; Toni, Danilo; Yperzeele, Laetitia; Weitzel, Paul; Sampaio, Gisele; Avezum, Alvaro; Dawson, Jesse; Strbian, Daniel; Tatlisumak, Turgut; Eckstein, Jens; Ameriso, Sebastián; Weber, Joerg; Sandset, Else; Pogosova, Nana; Lavados, Pablo; Arauz, Antonio; Gailani, David; Diener, Hans-Christoph; Bernstein, Richard; Cordonnier, Charlotte; Kahl, Anja; Abelian, Grigor; Donovan, Mark; Pachai, Chahin; Li, Danshi; Hankey, GraemeBackground: People with factor XI deficiency have lower rates of ischaemic stroke than the general population and infrequent spontaneous bleeding, suggesting that factor XI has a more important role in thrombosis than in haemostasis. Milvexian, an oral small-molecule inhibitor of activated factor XI, added to standard antiplatelet therapy, might reduce the risk of non-cardioembolic ischaemic stroke without increasing the risk of bleeding. We aimed to estimate the dose-response of milvexian for recurrent ischaemic cerebral events and major bleeding in patients with recent ischaemic stroke or transient ischaemic attack (TIA). Methods: AXIOMATIC-SSP was a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial done at 367 hospitals in 27 countries. Eligible participants aged 40 years or older, with acute (<48 h) ischaemic stroke or high-risk TIA, were randomly assigned by a web-based interactive response system in a 1:1:1:1:1:2 ratio to receive one of five doses of milvexian (25 mg once daily, 25 mg twice daily, 50 mg twice daily, 100 mg twice daily, or 200 mg twice daily) or matching placebo twice daily for 90 days. All participants received clopidogrel 75 mg daily for the first 21 days and aspirin 100 mg daily for the first 90 days. Investigators, site staff, and participants were masked to treatment assignment. The primary efficacy endpoint was the composite of ischaemic stroke or incident covert brain infarct on MRI at 90 days, assessed in all participants allocated to treatment who completed a follow-up MRI brain scan, and the primary analysis assessed the dose-response relationship with Multiple Comparison Procedure-Modelling (MCP-MOD). The main safety outcome was major bleeding at 90 days, assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov (NCT03766581) and the EU Clinical Trials Register (2017-005029-19). Findings: Between Jan 27, 2019, and Dec 24, 2021, 2366 participants were randomly allocated to placebo (n=691); milvexian 25 mg once daily (n=328); or twice-daily doses of milvexian 25 mg (n=318), 50 mg (n=328), 100 mg (n=310), or 200 mg (n=351). The median age of participants was 71 (IQR 62-77) years and 859 (36%) were female. At 90 days, the estimates of the percentage of participants with either symptomatic ischaemic stroke or covert brain infarcts were 16·8 (90·2% CI 14·5-19·1) for placebo, 16·7 (14·8-18·6) for 25 mg milvexian once daily, 16·6 (14·8-18·3) for 25 mg twice daily, 15·6 (13·9-17·5) for 50 mg twice daily, 15·4 (13·4-17·6) for 100 mg twice daily, and 15·3 (12·8-19·7) for 200 mg twice daily. No significant dose-response was observed among the five milvexian doses for the primary composite efficacy outcome. Model-based estimates of the relative risk with milvexian compared with placebo were 0·99 (90·2% CI 0·91-1·05) for 25 mg once daily, 0·99 (0·87-1·11) for 25 mg twice daily, 0·93 (0·78-1·11) for 50 mg twice daily, 0·92 (0·75-1·13) for 100 mg twice daily, and 0·91 (0·72-1·26) for 200 mg twice daily. No apparent dose-response was observed for major bleeding (four [1%] of 682 participants with placebo, two [1%] of 325 with milvexian 25 mg once daily, two [1%] of 313 with 25 mg twice daily, five [2%] of 325 with 50 mg twice daily, five [2%] of 306 with 100 mg twice daily, and five [1%] of 344 with 200 mg twice daily). Five treatment-emergent deaths occurred, four of which were considered unrelated to the study drug by the investigator. Interpretation: Factor XIa inhibition with milvexian, added to dual antiplatelet therapy, did not substantially reduce the composite outcome of symptomatic ischaemic stroke or covert brain infarction and did not meaningfully increase the risk of major bleeding. Findings from our study have informed the design of a phase 3 trial of milvexian for the prevention of ischaemic stroke in patients with acute ischaemic stroke or TIA.Item Timing of Recanalization and Functional Recovery in Acute Ischemic Stroke(2020) Tsivgoulis, Georgios; Saqqur, Maher; Sharma, Vijay K.; Brunser, Alejandro; Eggers, Jürgen; Mikulik, Robert; Katsanos, Aristeidis H.; Sergentanis, Theodore N.; Vadikolias, Konstantinos; Perren, Fabienne; Rubiera, Marta; Shahripour, Reza Bavarsad; Nguyen, Huy Thang; Martínez-Sánchez, Patricia; Safouris, Apostolos; Heliopoulos, Ioannis; Shuaib, Ashfaq; Derksen, Carol; Voumvourakis, Konstantinos; Psaltopoulou, Theodora; Alexandrov, Anne W.; Alexandrov, Andrei V.; CLOTBUST-PRO investigatorsBackground and Purpose Although onset-to-treatment time is associated with early clinical recovery in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (tPA), the effect of the timing of tPA-induced recanalization on functional outcomes remains debatable. Methods We conducted a multicenter, prospective observational cohort study to determine whether early (within 1-hour from tPA-bolus) complete or partial recanalization assessed during 2-hour real-time transcranial Doppler monitoring is associated with improved outcomes in patients with proximal occlusions. Outcome events included dramatic clinical recovery (DCR) within 2 and 24-hours from tPA-bolus, 3-month mortality, favorable functional outcome (FFO) and functional independence (FI) defined as modified Rankin Scale (mRS) scores of 0-1 and 0-2 respectively. Results We enrolled 480 AIS patients (mean age 66±15 years, 60% men, baseline National Institutes of Health Stroke Scale score 15). Patients with early recanalization (53%) had significantly (jos-2019-01648P<0.001) higher rates of DCR at 2-hour (54% vs. 10%) and 24-hour (63% vs. 22%), 3-month FFO (67% vs. 28%) and FI (81% vs. 39%). Three-month mortality rates (6% vs. 17%) and distribution of 3-month mRS scores were significantly lower in the early recanalization group. After adjusting for potential confounders, early recanalization was independently associated with higher odds of 3-month FFO (odds ratio [OR], 6.19; 95% confidence interval [CI], 3.88 to 9.88) and lower likelihood of 3-month mortality (OR, 0.34; 95% CI, 0.17 to 0.67). Onset to treatment time correlated to the elapsed time between tPA-bolus and recanalization (unstandardized linear regression coefficient, 0.13; 95% CI, 0.06 to 0.19). Conclusions Earlier tPA treatment after stroke onset is associated with faster tPA-induced recanalization. Earlier onset-to-recanalization time results in improved functional recovery and survival in AIS patients with proximal intracranial occlusions.Publication Validation of the transcranial Doppler rescue criteria for mechanical thrombectomy(2024) Khan, Adnan; Saqqur, Maher; Shuaib, Ashfaq; Khan, Khurshid; Sharma, Vijay; Brunser, Alejandro; Eggers, Jürgen; Mikulik, Robert; Katsanos, Aristeidis; Sergentanis, Theodore; Vadikolias, Konstantinos; Rubiera, Marta; Bavarsad, Reza; Thang, Huy; Martínez, Patricia; Safouris, Apostolos; Heliopoulos, Ioannis; Salam, Abdul; Derksen, Carol; Voumvourakis, Konstantinos; Psaltopoulou, Theodora; Alexandrov, Anne; Alexandrov, Andrei; Tsivgoulis, Georgios; CLOTBUST-PRO InvestigatorsBackground and purpose: Transcranial Doppler (TCD) identifies acute stroke patients with arterial occlusion where treatment may not effectively open the blocked vessel. This study aimed to examine the clinical utility and prognostic value of TCD flow findings in patients enrolled in a multicenter prospective study (CLOTBUST-PRO). Methods: Patients enrolled with intracranial occlusion on computed tomography angiography (CTA) who underwent urgent TCD evaluation before intravenous thrombolysis was included in this analysis. TCD findings were assessed using the mean flow velocity (MFV) ratio, comparing the reciprocal ratios of the middle cerebral artery (MCA) depths bilaterally (affected MCA-to-contralateral MCA MFV [aMCA/cMCA MFV ratio]). Results: A total of 222 patients with intracranial occlusion on CTA were included in the study (mean age: 64 ± 14 years, 62% men). Eighty-eight patients had M1 MCA occlusions; baseline mean National Institutes of Health Stroke Scale (NIHSS) score was 16, and a 24-hour mean NIHSS score was 10 points. An aMCA/cMCA MFV ratio of <.6 had a sensitivity of 99%, specificity of 16%, positive predictive value (PV) of 60%, and negative PV of 94% for identifying large vessel occlusion (LVO) including M1 MCA, terminal internal carotid artery, or tandem ICA/MCA. Thrombolysis in Brain Ischemia scale, with (grade ≥1) compared to without flow (grade 0), showed a sensitivity of 17.1%, specificity of 86.9%, positive PV of 62%, and negative PV of 46% for identifying LVO. Conclusions: TCD is a valuable modality for evaluating arterial circulation in acute ischemic stroke patients, demonstrating significant potential as a screening tool for intravenous/intra-arterial lysis protocols.