Randomized Controlled Trial

. 2022 Mar;53(3):728-738.

doi: 10.1161/STROKEAHA.121.037541. Epub 2022 Feb 10.

Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT): A Multicenter International Study

Shadi Yaghi¹, Liqi Shu¹, Ekaterina Bakradze², Setareh Salehi Omran³, James A Giles⁴, Jordan Y Amar⁴, Nils Henninger^{5

6}, Marwa Elnazeir⁵, Ava L Liberman⁷, Khadean Moncrieffe⁸, Jenny Lu⁸, Richa Sharma⁹, Yee Cheng⁹, Adeel S Zubair⁹, Alexis N Simpkins¹⁰, Grace T Li¹⁰, Justin Chi Kung¹⁰, Dezaray Perez¹⁰, Mirjam Heldner¹¹, Adrian Scutelnic¹¹, David Seiffge¹¹, Bernhard Siepen¹¹, Aaron Rothstein¹², Ossama Khazaal¹², David Do¹², Sami Al Kasab^{13

14}, Line Abdul Rahman¹³, Eva A Mistry¹⁵, Deborah Kerrigan¹⁶, Hayden Lafever¹⁶, Thanh N Nguyen¹⁷, Piers Klein^{15

17}, Hugo Aparicio¹⁷, Jennifer Frontera¹⁸, Lindsey Kuohn¹⁸, Shashank Agarwal¹⁸, Christoph Stretz¹, Narendra Kala¹, Sleiman El Jamal¹, Alison Chang¹, Shawna Cutting¹, Han Xiao¹⁹, Adam de Havenon⁹, Varsha Muddasani²⁰, Teddy Wu²¹, Duncan Wilson²¹, Amre Nouh²², Syed Daniyal Asad²², Abid Qureshi²³, Justin Moore²³, Pooja Khatri, Yasmin Aziz¹⁵, Bryce Casteigne¹⁵, Muhib Khan²⁴, Yao Cheng²⁴, Brian Mac Grory²⁵, Martin Weiss²⁵, Dylan Ryan²⁵, Maria Cristina Vedovati²⁶, Maurizio Paciaroni²⁷, James E Siegler²⁸, Scott Kamen²⁸, Siyuan Yu²⁸, Christopher R Leon Guerrero²⁹, Eugenie Atallah²⁹, Gian Marco De Marchis³⁰, Alex Brehm³¹, Tolga Dittrich³⁰, Marios Psychogios³¹, Ronald Alvarado-Dyer³², Tareq Kass-Hout³², Shyam Prabhakaran³², Tristan Honda³³, David S Liebeskind³³, Karen Furie¹

Affiliations

¹ Department of Neurology, Brown University, Providence, RI (S.Y., L.S., C.S., N.K., S.E.J., A.C., S.C., K.F.).
² Department of Neurology, University of Alabama at Birmingham (E.B.).
³ Department of Neurology, University of Colorado School of Medicine, Aurora (S.S.O.).
⁴ Department of Neurology, Washington University, Saint Louis, MO (J.A.G., J.Y.A.).
⁵ Department of Neurology (N.H., M.E.), University of Massachusetts, Worcester.
⁶ Department of Psychiatry (N.H.), University of Massachusetts, Worcester.
⁷ Department of Neurology, Weill Cornell Medical Center, NY (A.L.L.).
⁸ Department of Neurology, Montefiore Medical Center, NY (K.M., J.L.).
⁹ Department of Neurology, Yale University, New Haven, CT (R.S., Y.C., A.S.Z., A.d.H.).
¹⁰ Department of Neurology, University of Florida, Gainesville (A.N.S., G.T.L., J.C.K., D.P.).
¹¹ Department of Neurology, Inselspital Universitätsspital, Bern, Switzerland (M.H., A.S., D.S., B.S.).
¹² Department of Neurology, University of Pennsylvania, Philadelphia, PA (A.R., O.K., D.D.).
¹³ Department of Neurology (S.A.K., L.A.R.), Medical University of South Carolina, Charleston.
¹⁴ Department of Neurosurgery (S.A.K.), Medical University of South Carolina, Charleston.
¹⁵ Department of Neurology and Rehabilitation Medicine, University of Cincinnati (E.A.M., P.K., Y.A., B.C.).
¹⁶ Department of Neurology, Vanderbilt University, Nashville, TN (D.K., H.L.).
¹⁷ Department of Neurology, Boston University School of Medicine, MA (T.N.N., P.K., H.A.).
¹⁸ Department of Neurology, New York University, NY (J.F., L.K., S.A.).
¹⁹ Department of Biostatistics, University of California Santa Barbara (H.X.).
²⁰ Department of Neurology, University of Utah, Salt Lake City (V.M.).
²¹ Department of Neurology, Christchurch hospital, New Zealand (T.W., D.W.).
²² Department of Neurology, Hartford Hospital, CT (A.N., S.D.A.).
²³ Department of Neurology, University of Kansas, Kansas City (A.Q., J.M.).
²⁴ Department of Neurology, Spectrum Health, Michigan State University, Grand Rapids (M.K., Y.C.).
²⁵ Department of Neurology, Duke University, Durham, NC (B.M.G., M.W., D.R.).
²⁶ Department of Medicine and Surgery, University of Perugia, Italy (M.C.V.).
²⁷ Neurology - Stroke Unit, IRCCS MultiMedica, Milano, Italy (M.P.).
²⁸ Department of Neurology, Cooper University, Camden, NJ (J.E.S., S.K., S.Y.).
²⁹ Department of Neurology, George Washington University, District of Columbia (C.R.L.G., E.A.).
³⁰ Department of Neurology, University Hospital Basel and University of Basel, Switzerland (G.M.D.M., T.D.).
³¹ Department of interventional and diagnostic Neuroradiology, Clinic of Radiology and Nuclear Medicine, University Hospital Basel and University of Basel, Switzerland (A.B., M.P.).
³² Department of Neurology, University of Chicago, IL (R.A.-D., T.K.-H., S.P.).
³³ Department of Neurology, University of California at Los Angeles (T.H., D.S.L.).

PMID: 35143325
DOI: 10.1161/STROKEAHA.121.037541

Free article

Randomized Controlled Trial

Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT): A Multicenter International Study

Shadi Yaghi et al. Stroke. 2022 Mar.

Free article

. 2022 Mar;53(3):728-738.

doi: 10.1161/STROKEAHA.121.037541. Epub 2022 Feb 10.

Authors

Affiliations

¹ Department of Neurology, Brown University, Providence, RI (S.Y., L.S., C.S., N.K., S.E.J., A.C., S.C., K.F.).
² Department of Neurology, University of Alabama at Birmingham (E.B.).
³ Department of Neurology, University of Colorado School of Medicine, Aurora (S.S.O.).
⁴ Department of Neurology, Washington University, Saint Louis, MO (J.A.G., J.Y.A.).
⁵ Department of Neurology (N.H., M.E.), University of Massachusetts, Worcester.
⁶ Department of Psychiatry (N.H.), University of Massachusetts, Worcester.
⁷ Department of Neurology, Weill Cornell Medical Center, NY (A.L.L.).
⁸ Department of Neurology, Montefiore Medical Center, NY (K.M., J.L.).
⁹ Department of Neurology, Yale University, New Haven, CT (R.S., Y.C., A.S.Z., A.d.H.).
¹⁰ Department of Neurology, University of Florida, Gainesville (A.N.S., G.T.L., J.C.K., D.P.).
¹¹ Department of Neurology, Inselspital Universitätsspital, Bern, Switzerland (M.H., A.S., D.S., B.S.).
¹² Department of Neurology, University of Pennsylvania, Philadelphia, PA (A.R., O.K., D.D.).
¹³ Department of Neurology (S.A.K., L.A.R.), Medical University of South Carolina, Charleston.
¹⁴ Department of Neurosurgery (S.A.K.), Medical University of South Carolina, Charleston.
¹⁵ Department of Neurology and Rehabilitation Medicine, University of Cincinnati (E.A.M., P.K., Y.A., B.C.).
¹⁶ Department of Neurology, Vanderbilt University, Nashville, TN (D.K., H.L.).
¹⁷ Department of Neurology, Boston University School of Medicine, MA (T.N.N., P.K., H.A.).
¹⁸ Department of Neurology, New York University, NY (J.F., L.K., S.A.).
¹⁹ Department of Biostatistics, University of California Santa Barbara (H.X.).
²⁰ Department of Neurology, University of Utah, Salt Lake City (V.M.).
²¹ Department of Neurology, Christchurch hospital, New Zealand (T.W., D.W.).
²² Department of Neurology, Hartford Hospital, CT (A.N., S.D.A.).
²³ Department of Neurology, University of Kansas, Kansas City (A.Q., J.M.).
²⁴ Department of Neurology, Spectrum Health, Michigan State University, Grand Rapids (M.K., Y.C.).
²⁵ Department of Neurology, Duke University, Durham, NC (B.M.G., M.W., D.R.).
²⁶ Department of Medicine and Surgery, University of Perugia, Italy (M.C.V.).
²⁷ Neurology - Stroke Unit, IRCCS MultiMedica, Milano, Italy (M.P.).
²⁸ Department of Neurology, Cooper University, Camden, NJ (J.E.S., S.K., S.Y.).
²⁹ Department of Neurology, George Washington University, District of Columbia (C.R.L.G., E.A.).
³⁰ Department of Neurology, University Hospital Basel and University of Basel, Switzerland (G.M.D.M., T.D.).
³¹ Department of interventional and diagnostic Neuroradiology, Clinic of Radiology and Nuclear Medicine, University Hospital Basel and University of Basel, Switzerland (A.B., M.P.).
³² Department of Neurology, University of Chicago, IL (R.A.-D., T.K.-H., S.P.).
³³ Department of Neurology, University of California at Los Angeles (T.H., D.S.L.).

PMID: 35143325
DOI: 10.1161/STROKEAHA.121.037541

Abstract

Background: A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort.

Methods: This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups.

Results: Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140-720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51-1.73]; P=0.84), death (aHR, 0.78 [95% CI, 0.22-2.76]; P=0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48-1.73]; P=0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15-0.82]; P=0.02).

Conclusions: In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies.

Keywords: anticoagulants; contraindications; dabigatran; hemorrhage; venous thrombosis.

PubMed Disclaimer

Comment in

ACTION-CVT: Are the Findings ACTIONable?
Gorman JB, Field TS. Gorman JB, et al. Stroke. 2022 Mar;53(3):739-741. doi: 10.1161/STROKEAHA.122.038564. Epub 2022 Feb 10. Stroke. 2022. PMID: 35143324 No abstract available.

Cited by

Direct oral anticoagulants for treatment of venous thrombosis: illustrated review of appropriate use.
Khairani CD, Bejjani A, Assi A, Porio N, Talasaz AH, Piazza G, Cushman M, Bikdeli B. Khairani CD, et al. Res Pract Thromb Haemost. 2024 Apr 26;8(4):102424. doi: 10.1016/j.rpth.2024.102424. eCollection 2024 May. Res Pract Thromb Haemost. 2024. PMID: 38812988 Free PMC article.
Functional outcome predictors and recanalization in cerebral venous thrombosis: A single-center cross-sectional study.
Shahid R, Zafar A. Shahid R, et al. Turk J Emerg Med. 2024 Oct 1;24(4):218-225. doi: 10.4103/tjem.tjem_65_24. eCollection 2024 Oct-Dec. Turk J Emerg Med. 2024. PMID: 39564436 Free PMC article.
Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality.
Nguyen TN, Qureshi MM, Klein P, Yamagami H, Abdalkader M, Mikulik R, Sathya A, Mansour OY, Czlonkowska A, Lo H, Field TS, Charidimou A, Banerjee S, Yaghi S, Siegler JE, Sedova P, Kwan J, de Sousa DA, Demeestere J, Inoa V, Omran SS, Zhang L, Michel P, Strambo D, Marto JP, Nogueira RG; SVIN COVID-19 Global COVID Stroke Registry; Kristoffersen ES, Tsivgoulis G, Lereis VP, Ma A, Enzinger C, Gattringer T, Rahman A, Bonnet T, Ligot N, De Raedt S, Lemmens R, Vanacker P, Vandervorst F, Conforto AB, Hidalgo RCT, Mora Cuervo DL, de Oliveira Neves L, Lameirinhas da Silva I, Martíns RT, Rebello LC, Santiago IB, Sakelarova T, Kalpachki R, Alexiev F, Cora EA, Kelly ME, Peeling L, Pikula A, Chen HS, Chen Y, Yang S, Roje Bedekovic M, Čabal M, Tenora D, Fibrich P, Dušek P, Hlaváčová H, Hrabanovska E, Jurák L, Kadlčíková J, Karpowicz I, Klečka L, Kovář M, Neumann J, Paloušková H, Reiser M, Rohan V, Šimůnek L, Skoda O, Škorňa M, Šrámek M, Drenck N, Sobh K, Lesaine E, Sabben C, Reiner P, Rouanet F, Strbian D, Boskamp S, Mbroh J, Nagel S, Rosenkranz M, Poli S, Thomalla G, Karapanayiotides T, Koutroulou I, Kargiotis O, Palaiodimou L, Barrientos Guerra JD, Huded V, Nagendra S, Prajapati C, Sylaja PN, Sa… See abstract for full author list ➔ Nguyen TN, et al. J Stroke. 2022 May;24(2):256-265. doi: 10.5853/jos.2022.00752. Epub 2022 May 31. J Stroke. 2022. PMID: 35677980 Free PMC article.
Cerebral venous thrombosis.
Moraes Junior AAA, Conforto AB. Moraes Junior AAA, et al. Arq Neuropsiquiatr. 2022 May;80(5 Suppl 1):53-59. doi: 10.1590/0004-282X-ANP-2022-S108. Arq Neuropsiquiatr. 2022. PMID: 35976298 Free PMC article. Review.
Neurovascular complications of antiphospholipid syndrome: a narrative review.
Mendes GNN, Morais ABCG, Gioia LC, Jacquin G, Poppe AY, Soga FH, Andrade JBC. Mendes GNN, et al. Arq Neuropsiquiatr. 2024 Dec;82(12):1-7. doi: 10.1055/s-0044-1793932. Epub 2024 Dec 10. Arq Neuropsiquiatr. 2024. PMID: 39658037 Free PMC article. Review.

See all "Cited by" articles

Publication types

Actions
Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
Medical
- ClinicalTrials.gov
- 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

Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT): A Multicenter International Study

Affiliations

Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT): A Multicenter International Study

Authors

Affiliations

Abstract

Comment in

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous

Abstract

Comment in

Similar articles

Cited by

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous