Objectives Current guidelines do not recommend direct oral anticoagulants (DOAC) to treat cerebral venous thrombosis (CVT) despite their benefits over standard therapy. We performed a systematic review to summarize the published experience of DOAC therapy in CVT. Data sources MEDLINE, EMBASE, and COCHRANE databases up to November 18, 2020. Eligibility criteria All published articles of patients with CVT treated with DOAC were included. Studies without follow-up information were excluded. Data extraction and synthesis Two independent reviewers screened articles and extracted data. A risk of bias analysis was performed. Primary and secondary outcome measures Safety data included mortality, intracranial hemorrhage (ICH), or other adverse events. Efficacy data included recurrent CVT, recanalization rates, and disability by modified Rankin Scales (mRS). Results 33 studies met inclusion criteria. One randomized controlled trial, 5 observational cohorts, and 27 case series or studies reported 279 patients treated with DOAC for CVT: 41% dabigatran, 47% rivaroxaban, 10% apixaban, and 2% edoxaban, in addition to 315 patients treated with standard therapy. The observational cohorts showed a similar risk of death in DOAC and standard therapy arms (RR 2.12, 95%CI 0.29-15.59). New ICH was reported in 2 (0.7%) DOAC-treated patients and recurrent CVT occurred in 4 (1.5%). A favourable mRS between 0 and 2 was reported in 94% of DOAC-treated patients, more likely than standard therapy in observational cohorts (RR 1.13, 95% CI: 1.02-1.25). Conclusion The evidence for DOAC use in CVT is limited although suggests sufficient safety and efficacy despite variability in timing and dose of treatment. This systematic review highlights that further rigorous trials are needed to validate these findings and to determine optimal treatment regimens. PROSPERO ID: CRD42017078398

The search strategy was iteratively developed with assistance of a research librarian (RS). We searched Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R), EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials for original reports of patients with a diagnosis of CVT treated with a DOAC up to November 18, 2020. We included all available peer-reviewed studies including RCTs, prospective or retrospective observational cohorts, case series and case studies. Studies without follow-up data were excluded. Two authors (GB, JG) independently reviewed titles and abstracts for inclusion.  Authors were contacted for additional information if necessary.

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