Observational Study

. 2023 Dec;8(4):1030-1040.

doi: 10.1177/23969873231186863. Epub 2023 Jul 15.

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

Maurizio Paciaroni¹, Valeria Caso¹, Michele Romoli², Cecilia Becattini¹, Alexander Salerno³, Costanza Rapillo^{3

4}, Fanny Simonnet³, Davide Strambo³, Isabella Canavero^{5

6}, Marialuisa Zedde⁷, Rosario Pascarella⁸, Sung-Il Sohn⁹, Simona Sacco¹⁰, Raffaele Ornello¹⁰, Kristian Barlinn¹¹, Daniela Schoene¹¹, Jan Rahmig¹¹, Maria Giulia Mosconi¹, Ilaria Leone De Magistris¹, Andrea Alberti¹, Michele Venti¹, Giorgio Silvestrelli¹², Alfonso Ciccone¹², Marina Padroni¹³, Michele Laudisi¹³, Andrea Zini¹⁴, Luana Gentile¹⁴, Odysseas Kargiotis¹⁵, Georgios Tsivgoulis¹⁶, Rossana Tassi¹⁷, Francesca Guideri¹⁷, Maurizio Acampa¹⁷, Luca Masotti¹⁸, Elisa Grifoni¹⁸, Alessandro Rocco¹⁹, Marina Diomedi¹⁹, Theodore Karapanayiotides²⁰, Stefan T Engelter^{21

22}, Alexandros A Polymeris²¹, Annaelle Zietz²¹, Fabio Bandini²³, Pietro Caliandro²⁴, Giuseppe Reale²⁴, Marco Moci²⁴, Aurelia Zauli²⁵, Manuel Cappellari²⁶, Andrea Emiliani²⁶, Antonio Gasparro²⁷, Valeria Terruso²⁷, Marina Mannino²⁷, Elisa Giorli²⁸, Danilo Toni²⁹, Marco Andrighetti²⁹, Anne Falcou³⁰, Lina Palaiodimou¹⁶, George Ntaios³¹, Dimitrios Sagris³¹, Efstathia Karagkiozi³¹, Anastasia Adamou³¹, Panagiotis Halvatsiotis³², Yuriy Flomin³³, Umberto Scoditti³⁴, Antonio Genovese³⁴, Nemanja Popovic³⁵, Leonardo Pantoni³⁶, Francesco Mele³⁶, Nicola Molitierno³⁶, Piergiorgio Lochner³⁷, Alessandro Pezzini³⁸, Massimo Del Sette³⁹, Davide Sassos³⁹, Sotirios Giannopoulos⁴⁰, Maria Kosmidou⁴⁰, Evangelos Ntais⁴⁰, Enrico Maria Lotti⁴¹, Vincenzo Mastrangelo⁴¹, Alberto Chiti⁴², Andrea Naldi⁴³, Peter Vanacker^{44

45

46}, Mario Ferrante⁴⁷, Vera Volodina⁴⁸, Michelangelo Mancuso⁴⁹, Nicola Giannini⁴⁹, Marco Baldini⁴⁹, Kostantinos Vadikolias⁵⁰, Sofia Kitmeridou⁵⁰, Carlo Emanuele Saggese⁵¹, Tiziana Tassinari⁵², Valentina Saia⁵², Patrik Michel²

Affiliations

¹ Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Perugia, Italy.
² Neurology and Stroke Unit, Department of Neuroscience, Bufalini Hospital, Cesena, Italy.
³ Stroke Center, Neurology Service,Department of Clinical Neuroscience, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁴ Stroke Unit, Careggi University Hospital, Florence, Italy.
⁵ Emergency Neurology, IRCCS Casimiro Mondino Foundation, Pavia, Italy.
⁶ Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta," Milano, Italy.
⁷ Neurology Unit, AUSL - IRCCS of Reggio Emilia, Reggio Emilia, Italy.
⁸ SSD Neuroradiologia, AUSL - IRCCS of Reggio Emila, Reggio Emilia, Italy.
⁹ Department of Neurology, Keimyung University School of Medicine, Daegu, South Korea.
¹⁰ Neuroscience Section, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
¹¹ Department of Neurology, Dresden University Stroke Center, Dresden, Germany.
¹² S.C. di Neurologia e S.S. di Stroke Unit, ASST di Mantova, Mantova, Italy.
¹³ Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy.
¹⁴ IRCCS Istituto delle Scienze Neurologiche di Bologna, Department of Neurology and Stroke Center, Maggiore Hospital, Bologna, Italy.
¹⁵ Stroke Unit, Metropolitan Hospital, Piraeus, Greece.
¹⁶ Second Department of Neurology, "Attikon" Hospital, National & Kapodistrian University of Athens, School of Medicine, Athens, Greece.
¹⁷ Stroke Unit, AOU Senese, Siena, Italy.
¹⁸ Internal Medicine, San Giuseppe Hospital, Empoli, Italy.
¹⁹ Stroke Unit, Department of Systems Medicine, University of Tor Vergata, Rome, Italy.
²⁰ 2nd Department of Neurology, AHEPA University Hospital, Thessaloniki, Greece.
²¹ Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.
²² Neurology and Neurorehabilitation, University Department of Geriatric Medicine FELIX PLATTER, University of Basel, Basel, Switzerland.
²³ Department of Neurology, ASL 3 Genovese, Genova, Italy.
²⁴ Neurology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
²⁵ Department of Geriatrics, Neurosciences and Orthopedics, Università Cattolica del Sacro Cuore, Rome, Italy.
²⁶ Stroke Unit, DAI di Neuroscienze, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
²⁷ Neurologia, Ospedali Riuniti, Palermo, Italy.
²⁸ Stroke Unit, Department of Neurology, Sant'Andrea Hospital, La Spezia, Italy.
²⁹ Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.
³⁰ Stroke Unit - Emergency Department, Policlinico Umberto I, Rome, Italy.
³¹ Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
³² Second Department of Internal Medicine-Propaedeutic and Diabetes Center, Medical School, University General Hospital "Attikon," National and Kapodistrian University of Athens, Greece.
³³ Stroke and Neurorehabilitation Unit MC 'Universal Clinic "Oberig" Kyiv, Kyiv, Ukraine.
³⁴ Stroke Unit, Emergency Department, University of Parma, Parma, Italy.
³⁵ Clinic of Neurology, University Clinical Center of Vòsvodina, University of Novi Sad, Novi Sad, Serbia.
³⁶ Department of Biomedical and Clinical Sciences, University of Milano, Milano, Italy.
³⁷ Department of Neurology, Saarland University, Medical Center, Homburg, Germany.
³⁸ Department of Clinical and Experimental Sciences, Neurology Unit, University of Brescia, Brescia, Italy.
³⁹ IRCCS Ospedale Policlinico San Martino, Genova, Italy.
⁴⁰ Department of Neurology, University of Ioannina School of Medicine, Ioannina, Greece.
⁴¹ Neurology Unit, "Infermi" Hospital, AUSL Romagna, Rimini, Italy.
⁴² Neurologia, Ospedale Apuano, Massa Carrara, Italy.
⁴³ Neurology Unit, San Giovanni Bosco Hospital, Turin, Italy.
⁴⁴ NeuroVascular Center and Stroke Unit Antwerp, Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.
⁴⁵ Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
⁴⁶ Groeninge Hospital, Kortrijk, Belgium.
⁴⁷ Operative Research Unit of Neurology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.
⁴⁸ Municipal Budgetary Healthcare Institution of Novosibirsk, City Clinical Hospital # 1, Novosibirsk (Russia) at the Novosibirsk State Medical University, Novosibirsk, Russia.
⁴⁹ Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy.
⁵⁰ Department of Neurology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
⁵¹ Unità di Terapia Neurovascolare, Ospedale "Fabrizio Spaziani," Frosinone, Italy.
⁵² Department of Neurology and Stroke Unit, Santa Corona Hospital, Pietra Ligure (Savona), Italy.

PMID: 37452632
PMCID: PMC10683741
DOI: 10.1177/23969873231186863

Observational Study

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

Maurizio Paciaroni et al. Eur Stroke J. 2023 Dec.

. 2023 Dec;8(4):1030-1040.

doi: 10.1177/23969873231186863. Epub 2023 Jul 15.

Authors

Affiliations

¹ Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Perugia, Italy.
² Neurology and Stroke Unit, Department of Neuroscience, Bufalini Hospital, Cesena, Italy.
³ Stroke Center, Neurology Service,Department of Clinical Neuroscience, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁴ Stroke Unit, Careggi University Hospital, Florence, Italy.
⁵ Emergency Neurology, IRCCS Casimiro Mondino Foundation, Pavia, Italy.
⁶ Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta," Milano, Italy.
⁷ Neurology Unit, AUSL - IRCCS of Reggio Emilia, Reggio Emilia, Italy.
⁸ SSD Neuroradiologia, AUSL - IRCCS of Reggio Emila, Reggio Emilia, Italy.
⁹ Department of Neurology, Keimyung University School of Medicine, Daegu, South Korea.
¹⁰ Neuroscience Section, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
¹¹ Department of Neurology, Dresden University Stroke Center, Dresden, Germany.
¹² S.C. di Neurologia e S.S. di Stroke Unit, ASST di Mantova, Mantova, Italy.
¹³ Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy.
¹⁴ IRCCS Istituto delle Scienze Neurologiche di Bologna, Department of Neurology and Stroke Center, Maggiore Hospital, Bologna, Italy.
¹⁵ Stroke Unit, Metropolitan Hospital, Piraeus, Greece.
¹⁶ Second Department of Neurology, "Attikon" Hospital, National & Kapodistrian University of Athens, School of Medicine, Athens, Greece.
¹⁷ Stroke Unit, AOU Senese, Siena, Italy.
¹⁸ Internal Medicine, San Giuseppe Hospital, Empoli, Italy.
¹⁹ Stroke Unit, Department of Systems Medicine, University of Tor Vergata, Rome, Italy.
²⁰ 2nd Department of Neurology, AHEPA University Hospital, Thessaloniki, Greece.
²¹ Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.
²² Neurology and Neurorehabilitation, University Department of Geriatric Medicine FELIX PLATTER, University of Basel, Basel, Switzerland.
²³ Department of Neurology, ASL 3 Genovese, Genova, Italy.
²⁴ Neurology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
²⁵ Department of Geriatrics, Neurosciences and Orthopedics, Università Cattolica del Sacro Cuore, Rome, Italy.
²⁶ Stroke Unit, DAI di Neuroscienze, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
²⁷ Neurologia, Ospedali Riuniti, Palermo, Italy.
²⁸ Stroke Unit, Department of Neurology, Sant'Andrea Hospital, La Spezia, Italy.
²⁹ Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.
³⁰ Stroke Unit - Emergency Department, Policlinico Umberto I, Rome, Italy.
³¹ Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
³² Second Department of Internal Medicine-Propaedeutic and Diabetes Center, Medical School, University General Hospital "Attikon," National and Kapodistrian University of Athens, Greece.
³³ Stroke and Neurorehabilitation Unit MC 'Universal Clinic "Oberig" Kyiv, Kyiv, Ukraine.
³⁴ Stroke Unit, Emergency Department, University of Parma, Parma, Italy.
³⁵ Clinic of Neurology, University Clinical Center of Vòsvodina, University of Novi Sad, Novi Sad, Serbia.
³⁶ Department of Biomedical and Clinical Sciences, University of Milano, Milano, Italy.
³⁷ Department of Neurology, Saarland University, Medical Center, Homburg, Germany.
³⁸ Department of Clinical and Experimental Sciences, Neurology Unit, University of Brescia, Brescia, Italy.
³⁹ IRCCS Ospedale Policlinico San Martino, Genova, Italy.
⁴⁰ Department of Neurology, University of Ioannina School of Medicine, Ioannina, Greece.
⁴¹ Neurology Unit, "Infermi" Hospital, AUSL Romagna, Rimini, Italy.
⁴² Neurologia, Ospedale Apuano, Massa Carrara, Italy.
⁴³ Neurology Unit, San Giovanni Bosco Hospital, Turin, Italy.
⁴⁴ NeuroVascular Center and Stroke Unit Antwerp, Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.
⁴⁵ Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
⁴⁶ Groeninge Hospital, Kortrijk, Belgium.
⁴⁷ Operative Research Unit of Neurology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.
⁴⁸ Municipal Budgetary Healthcare Institution of Novosibirsk, City Clinical Hospital # 1, Novosibirsk (Russia) at the Novosibirsk State Medical University, Novosibirsk, Russia.
⁴⁹ Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy.
⁵⁰ Department of Neurology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
⁵¹ Unità di Terapia Neurovascolare, Ospedale "Fabrizio Spaziani," Frosinone, Italy.
⁵² Department of Neurology and Stroke Unit, Santa Corona Hospital, Pietra Ligure (Savona), Italy.

PMID: 37452632
PMCID: PMC10683741
DOI: 10.1177/23969873231186863

Abstract

Introduction: The best therapeutic strategy for patients with mechanical heart valves (MHVs) having acute ischemic stroke during treatment with vitamin K antagonists (VKAs) remain unclear. Being so, we compared the outcomes for: (i) full dose heparin along with VKA (bridging therapy group) and (ii) restarting VKA without heparin (nonbridging group).

Patients and methods: For this multicenter observational cohort study, data on consecutive acute ischemic stroke patients with MHV was retrospectively collected from prospective registries. Propensity score matching (PSM) was adopted to adjust for any treatment allocation confounders. The primary outcome was the composite of stroke, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding at 90 days.

Results: Overall, 255 out of 603 patients (41.3%) received bridging therapy: 36 (14.1%) had combined outcome, compared with 28 (8.0%) in the nonbridging group (adjusted OR 1.83; 95% CI 1.05-3.18; p = 0.03). Within the bridging group, 13 patients (5.1%) compared to 12 (3.4%) in the nonbridging group had an ischemic outcome (adjusted OR 1.71; 95% CI 0.84-3.47; p = 0.2); major bleedings were recorded in 23 (9.0%) in the bridging group and 16 (4.6%) in the nonbridging group (adjusted OR 1.88; 95% CI 0.95-3.73; p = 0.07). After PSM, 36 (14.2%) of the 254 bridging patients had combined outcome, compared with 23 (9.1%) of 254 patients in the nonbridging group (OR 1.66; 95% CI 0.95-2.85; p = 0.07).

Conclusion: Acute ischemic stroke patients with MHV undergoing bridging therapy had a marginally higher risk of ischemic or hemorrhagic events, compared to nonbridging patients.

Keywords: Mechanical heart valve; acute stroke; oral anticoagulants; prevention.

PubMed Disclaimer

Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Paciaroni received honoraria as a member of the speaker bureau of Sanofi-Aventis, Bristol Meyer Squibb, Daiiki Sankyo and Pfizer. Becattini received honoraria as a member of the speaker bureau of Bristol Meyer Squibb and Bayer. Michel received research grant by Swiss National Science Foundation, Swiss Heart Foundation and University of Lausanne. Tsivgoulis has received funding for travel or speaker’s honoraria from Bayer, Pfizer, and Boehringer Ingelheim. He has served on scientific advisory boards for Bayer, Boehringer Ingelheim, and Daiichi Sankyo. Toni has received personal fees from Abbott, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, and Pfizer. Caso received honoraria as a member of the speaker bureau of Boehringer Ingelheim, Bayer, and Daiichi Sankyo (all fees were paid to Associazione Ricerca Stroke, Umbria). She received honoraria as consultant or advisory board member of Boehringer Ingelheim, Bayer, Daiichi Sankyo, and Pfizer. Ntaios reports speaker fees/advisory board/ research support from Bayer, Pfizer, Boehringer Ingelheim and Elpen. All fees are paid to his institution. Sacco has received personal fees as speaker or advisor from Abbott, Allergan, Astra Zeneca, Eli Lilly, Lundbeck, Novartis, NovoNordisk, Teva and research grants from Allergan, Novartis, and Uriach. Vanacker received honoraria as a member of the speaker bureau and as advisory board of Boehringer Ingelheim, Bristol Meyer Squibb, Daiichi Sankyo, Medtronic, EG and Pfizer. Del Sette has received honoraria for speaking from Bayer and Boehringer Ingelheim. Zedde received speaking and consulting fees from Daiichi Sankyo, Amicus Therapeutics, Sanofi Genzyme, Abbott, and Takeda. Cappellari has received consulting fees from Boehringer Ingelheim, Pfizer – Bristol Meyer Squibb, and Daiichi Sankyo. Flomin has received personal fees from Boehringer Ingelheim, Bayer and Takeda, grants, personal fees and nonfinancial support from Pfizer, personal fees and nonfinancial support from Sanofi Genzyme. Ornello has received nonfinancial support from Novartis, Allergan, and Teva. Giannopoulos has received funding for travel from Bayer and speaker’s honoraria from Pfizer. Zini has received consulting fees from Boehringer Ingelheim, CSL Behing and Alexion, Astra Zeneca. The other authors report no conflicts.

Figures

**Figure 1.**
Cumulative risk of combined, ischemic or hemorrhagic endpoint events in patients receiving or not bridging therapy.

**Figure 2.**
Cumulative risk of combined, ischemic or hemorrhagic endpoint events in patients receiving or not bridging therapy after Propensity Score Matching.

**Figure 3.**
Cumulative risk of combined, ischemic or hemorrhagic endpoint events stratified according to timing of anticoagulant therapy initiation in patients receiving or not bridging therapy.

See this image and copyright information in PMC

References

1. Altavilla R, Caso V, Bandini F, et al. Anticoagulation after stroke in patients with atrial fibrillation. Stroke 2019; 50: 2093–2100. - PubMed
1. Yaghi S, Mistry E, Liberman AL, et al. Anticoagulation type and early recurrence in cardioembolic stroke. Stroke 2020; 51: 2724–2732. - PMC - PubMed
1. Paciaroni M, Agnelli G, Micheli S, et al. Efficacy and safety of anticoagulant treatment in acute cardioembolic stroke: a meta-analysis of randomized controlled trials. Stroke 2007; 38: 423–430. - PubMed
1. Wolpert SM, Bruckmann H, Greenlee R, et al. Neuroradiologic evaluation of patients with acute stroke treated with recombinant tissue plasminogen activator. The rt-PA Acute Stroke Study Group. AJNR Am J Neuroradiol 1993; 14: 3–13. - PMC - PubMed
1. Paciaroni M, Agnelli G, Corea F, et al. Early hemorrhagic transformation of brain infarction: rate, predictive factors, and influence on clinical outcome: results of a prospective multicenter study. Stroke 2008; 39: 2249–2256. - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous