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Resuming anticoagulants after anticoagulation-associated intracranial haemorrhage: systematic review and meta-analysis.

ABSTRACT: OBJECTIVE:To determine the adverse outcomes following resumption of anticoagulation in patients with anticoagulation-associated intracranial haemorrhage (ICH). DESIGN:We performed a systematic review and meta-analysis in this clinical population. The Preferred Reporting Items for Systemic Reviews and Meta-Analyses statement was followed, and two authors independently assessed eligibility of all retrieved studies and extracted data. DATA SOURCES:Medline, Embase and the Cochrane Central Register of Controlled Trials, from inception to February 2017. ELIGIBILITY CRITERIA AND OUTCOMES:Randomised controlled trials or cohort studies that recruited adults who received oral anticoagulants at the time of ICH occurrence and survived after the acute phase or hospitalisation were searched. Primary outcomes, including long-term mortality, recurrent ICH and thromboembolic events. Secondary outcomes were the frequency of resuming anticoagulant therapy and related factors. RESULTS:We included 12 cohort studies (no clinical trials) involving 3431 ICH participants. The pooled frequency of resuming anticoagulant therapy was 38% (95% CI 32% to 44%), but this was higher in participants with prosthetic heart valves, subarachnoid haemorrhage or dyslipidaemia. There was no evidence that resuming anticoagulant therapy was associated with higher long-term mortality (pooled relative risk (RR) 0.60, 95%?CI 0.30 to 1.19; p=0.14) or ICH recurrence (pooled RR 1.14, 95%?CI 0.72 to 1.80; p=0.57). Resumption of anticoagulation was associated with significantly fewer thromboembolic events (pooled RR 0.31, 95%?CI 0.23 to 0.42; p<0.001). In a subgroup of patients with atrial fibrillation, resuming anticoagulant therapy was associated with fewer long-term mortality (pooled RR 0.27, 95%?CI 0.20 to 0.37, p<0.001). CONCLUSIONS:Based on these observational studies, resuming anticoagulant therapy after anticoagulation-associated ICH has beneficial effects on long-term complications. Clinical trials are needed to substantiate these findings. PROSPERO REGISTRATION NUMBER:CRD42017063827.

SUBMITTER: Zhou Z

PROVIDER: S-EPMC5961574 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Resuming anticoagulants after anticoagulation-associated intracranial haemorrhage: systematic review and meta-analysis.

Zhou Zien Z Yu Jie J Carcel Cheryl C Delcourt Candice C Shan Jiehui J Lindley Richard I RI Neal Bruce B Anderson Craig S CS Hackett Maree L ML

BMJ open 20180514 5

<h4>Objective</h4>To determine the adverse outcomes following resumption of anticoagulation in patients with anticoagulation-associated intracranial haemorrhage (ICH).<h4>Design</h4>We performed a systematic review and meta-analysis in this clinical population. The Preferred Reporting Items for Systemic Reviews and Meta-Analyses statement was followed, and two authors independently assessed eligibility of all retrieved studies and extracted data.<h4>Data sources</h4>Medline, Embase and the Cochr ...[more]

PMID: 29764874

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Project description:AbstractGlobally, 32% to 70% patients with atrial fibrillation (AF) are prescribed oral anticoagulants (OACs) with warfarin for stroke prevention. However, patients with AF on OACs may experience intracranial hemorrhage (ICH), which presents a treatment dilemma. We therefore investigated whether resuming OACs in these patients is beneficial. Electronic medical records of patients with AF on OACs discharged with ICH between 2001 and 2013 were retrieved from the Taiwan National Health Insurance Research Database for analysis. We excluded patients who were <20 years old, who were not using OACs 6 months prior to ICH, or who had a CHA2DS2-VASc score of ≤1. We also excluded patients who died during admission for ICH, with follow-up for <6 weeks after discharge, or who started OAC >6 weeks after ICH diagnosis. The remaining patients were categorized into those who resumed OAC and those who discontinued OAC. Propensity score matching was performed between the 2 groups. Primary outcomes were mortality/ischemic stroke (IS)/systemic embolism (SE), IS/SE, and recurrent ICH at 6 months and 1 year. After the exclusion criteria were applied, 604 eligible patients (408 discontinued OAC and 196 resumed OAC within 6 weeks) were included in this study, and 186 patients in each group were 1:1 matched. Patients who resumed OAC had significantly lower mortality/IS/SE (hazard ratio [HR] = 0.39, 95% confidence interval [CI] = 0.20-0.76) and IS/SE (HR = 0.12, 95% CI = 0.03-0.53) at 6-month follow-up than patients who discontinued OAC. In addition, patients who resumed OAC had significantly lower mortality/IS/SE (HR = 0.56, 95% CI = 0.34-0.93) and IS/SE (HR = 0.26, 95% CI = 0.09-0.75) at 1-year follow-up. No difference in recurrent ICH was noted between the 2 groups. In conclusion, in patients with AF on OACs with ICH, resuming anticoagulant use was associated with significantly lower risks of composite outcomes of mortality/IS/SE and IS/SE than patients who discontinued OACs. No difference in recurrent ICH was observed between the 2 groups.

Project description:Background: The benefits and risks of starting anticoagulation therapy, such as direct oral anticoagulations (DOACs) or warfarin, in atrial fibrillation (AF) patients with a history of intracranial hemorrhage (ICH) remain controversial. We performed a systematic review and meta-analysis to compare the safety and efficacy of starting oral anticoagulation (OAC) and non-oral anticoagulation in these patients. Methods: PubMed, Cochrane Library, and Embase were searched from inception to 01 May 2022 for randomized controlled trials and cohort studies, reporting effectiveness and safety outcomes for anticoagulation therapy in atrial fibrillation patients with intracranial hemorrhage. The Newcastle-Ottawa Scale (NOS) and the Cochrane Collaboration tool were used to evaluate bias risks for all randomized controlled trials (RCTs) and cohort studies. An effects model was applied to calculate adjusted hazard ratios (aHRs) for randomized controlled trials and cohort studies. Results: We analyzed data from two randomized controlled trials (304 patients) and seven Cohort studies (17,477 patients). Compared to non-oral anticoagulation, starting oral anticoagulation therapy reduced the risk of Ischemic Stroke/Systemic Embolism (SE) (aHR: 0.64, 95% CI: 0.55-0.57) and all-cause death (aHR: 0.53, 95% CI: 0.35-0.80) in atrial fibrillation patients and a prior history intracranial hemorrhage. Starting oral anticoagulation therapy did not increase the risk of recurrent intracranial hemorrhage (aHR: 1.07, 95% CI: 0.66-1.74), but increased the risk of major bleeding (aHR: 1.38, 95% CI: 1.00-1.91) than no oral anticoagulation therapy. The DOACs had a lower risk of Ischemic Stroke/SE (aHR: 0.84, 95% CI: 0.70-1.00), recurrent intracranial hemorrhage (aHR: 0.63, 95% CI: 0.49-0.82), and all-cause death (aHR: 0.65, 95% CI: 0.48-0.88) compared to warfarin. According to subgroup analyses, starting oral anticoagulation therapy have a higher risk of recurrent intracranial hemorrhage than non-oral anticoagulation therapy (aHR: 1.57, 95% CI: 1.36-1.81) for Asians. Conclusion: After intracranial hemorrhage in atrial fibrillation patients, restarting or initiating oral anticoagulation therapy decreased the risk of Ischemic Stroke/SE and all-cause death but did not increase the risk for recurrent intracranial hemorrhage. Direct oral anticoagulations have better efficacy and safety than warfarin if oral anticoagulation therapy is started. However, starting oral anticoagulation increases the risk for recurrent intracranial hemorrhage in the Asian region.

Project description:Splanchnic vein thrombosis (SVT) is not rare in patients with acute pancreatitis. It remains unclear about whether anticoagulation should be given for acute pancreatitis-associated SVT. The PubMed, EMBASE, and Cochrane Library databases were searched. Rates of SVT recanalization, any bleeding, death, intestinal ischemia, portal cavernoma, and gastroesophageal varices were pooled and compared between patients with acute pancreatitis-associated SVT who received and did not receive therapeutic anticoagulation. Pooled rates and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Heterogeneity among studies was evaluated. Overall, 16 studies including 698 patients with acute pancreatitis-associated SVT were eligible. After therapeutic anticoagulation, the pooled rates of SVT recanalization, any bleeding, death, intestinal ischemia, portal cavernoma, and gastroesophageal varices were 44.3% (95%CI = 32.3%-56.6%), 10.7% (95%CI = 4.9%-18.5%), 13.3% (95%CI = 6.9%-21.4%), 16.8% (95%CI = 6.9%-29.9%), 21.2% (95%CI = 7.5%-39.5%), and 29.1% (95%CI = 16.1%-44.1%), respectively. Anticoagulation therapy significantly increased the rate of SVT recanalization (RR = 1.69; 95%CI = 1.29-2.19; P < .01), and marginally increased the risk of bleeding (RR = 1.98; 95%CI = 0.93-4.22; P = .07). The rates of death (RR = 1.42; 95%CI = 0.62-3.25; P = .40), intestinal ischemia (RR = 2.55; 95%CI = 0.23-28.16; P = .45), portal cavernoma (RR = 0.51; 95%CI = 0.21-1.22; P = .13), and gastroesophageal varices (RR = 0.71; 95%CI = 0.38-1.32; P = .28) were not significantly different between patients who received and did not receive anticoagulation therapy. Heterogeneity was statistically significant in the meta-analysis of intestinal ischemia, but not in those of SVT recanalization, any bleeding, death, portal cavernoma, or gastroesophageal varices. Anticoagulation may be effective for recanalization of acute pancreatitis-associated SVT, but cannot improve the survival. Randomized controlled trials are warranted to further investigate the clinical significance of anticoagulation therapy in such patients.

Project description:BACKGROUND:Antithrombotic (anticoagulant or antiplatelet) therapy is withheld from some patients with cerebral cavernous malformations, because of uncertainty around the safety of these drugs in such patients. We aimed to establish whether antithrombotic therapy is associated with an increased risk of intracranial haemorrhage in adults with cerebral cavernous malformations. METHODS:In this population-based, cohort study, we used data from the Scottish Audit of Intracranial Vascular Malformations, which prospectively identified individuals aged 16 years and older living in Scotland who were first diagnosed with a cerebral cavernous malformation during 1999-2003 or 2006-10. We compared the association between use of antithrombotic therapy after first presentation and the occurrence of intracranial haemorrhage or persistent or progressive focal neurological deficit due to the cerebral cavernous malformations during up to 15 years of prospective follow-up with multivariable Cox proportional hazards regression assessed in all individuals identified in the database. We also did a systematic review and meta-analysis, in which we searched Ovid MEDLINE and Embase from database inception to Feb 1, 2019, to identify comparative studies to calculate the intracranial haemorrhage incidence rate ratio according to antithrombotic therapy use. We then generated a pooled estimate using the inverse variance method and a random effects model. FINDINGS:We assessed 300 of 306 individuals with a cerebral cavernous malformation who were eligible for study. 61 used antithrombotic therapy (ten [16%] of 61 used anticoagulation) for a mean duration of 7·4 years (SD 5·4) during follow-up. Antithrombotic therapy use was associated with a lower risk of subsequent intracranial haemorrhage or focal neurological deficit (one [2%] of 61 vs 29 [12%] of 239, adjusted hazard ratio [HR] 0·12, 95% CI 0·02-0·88; p=0·037). In a meta-analysis of six cohort studies including 1342 patients, antithrombotic therapy use was associated with a lower risk of intracranial haemorrhage (eight [3%] of 253 vs 152 [14%] of 1089; incidence rate ratio 0·25, 95% CI 0·13-0·51; p<0·0001; I2=0%). INTERPRETATION:Antithrombotic therapy use is associated with a lower risk of intracranial haemorrhage or focal neurological deficit from cerebral cavernous malformations than avoidance of antithrombotic therapy. These findings provide reassurance about safety for clinical practice and require further investigation in a randomised controlled trial. FUNDING:UK Medical Research Council, Chief Scientist Office of the Scottish Government, The Stroke Association, Cavernoma Alliance UK, and the Remmert Adriaan Laan Foundation.

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Resuming anticoagulants after anticoagulation-associated intracranial haemorrhage: systematic review and meta-analysis.

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Resuming anticoagulants after anticoagulation-associated intracranial haemorrhage: systematic review and meta-analysis.

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