Novel oral anticoagulants(NOACs), which include direct thrombin inhibitor(dabigatran) and direct factor Xa inhibitors(rivaroxaban, apixaban and edoxaban), are gaining popularity in the prevention of embolic stroke in ...Novel oral anticoagulants(NOACs), which include direct thrombin inhibitor(dabigatran) and direct factor Xa inhibitors(rivaroxaban, apixaban and edoxaban), are gaining popularity in the prevention of embolic stroke in non-valvular atrial fibrillation as well as in the prevention and treatment of venous thromboembolism. However, similar to traditional anticoagulants, NOACs have the side effects of bleeding, including gastrointestinal bleeding(GIB). Results from both randomized clinical trials and observations studies suggest that high-dose dabigatran(150 mg b.i.d), rivaroxaban and high-dose edoxaban(60 mg daily) are associated with a higher risk of GIB compared with warfarin. Other risk factors of NOAC-related GIB include concomitant use of ulcerogenic agents, older age, renal impairment, Helicobacter pylori infection and a past history of GIB. Prevention of NOAC-related GIB includes proper patient selection, using a lower dose of certain NOACs and in patients with renal impairment, correction of modifiable risk factors, and prescription of gastroprotective agents. Overt GIB can be managed by withholding NOACs followed by delayed endoscopic treatment. In severe bleeding, additional measures include administration of activated charcoal, use of specific reversal agents such as idarucizumab for dabigatran and andexanent alfa for factor Xa inhibitors, and urgent endoscopic management.展开更多
Objective:Photoselective vaporization of the prostate(PVP)is a widely performed surgical procedure for benign prostatic obstruction.This approach has become particular favoured for men on anti-platelet and anticoagula...Objective:Photoselective vaporization of the prostate(PVP)is a widely performed surgical procedure for benign prostatic obstruction.This approach has become particular favoured for men on anti-platelet and anticoagulation agents such as clopidogrel and warfarin but there is minimal published experience in the setting of novel oral anticoagulants(NOACs).This study was to examine the perioperative outcomes in men on NOACs undergoing PVP,with particular reference to perioperative morbidity.Methods:A retrospective analysis of PVP datasets was undertaken from three centres in Sydney(Australia),Toulouse(France)and Boston(USA).Subjects who had been treated whilst on NOACs without discontinuation or bridging were identified.Perioperative outcomes and treatment parameters were examined and morbidity recorded according to Clavien-Dindo(CD)classification.Results:There were a total of 20 subjects who had undergone PVP whilst NOACs had been continued during the perioperative period.The mean age was 776.5 years.The mean prostate volume,energy utilization and vaporisation time was 9456 mL,301211 kJ,and 3521 min respectively.The mean postoperative duration of catheterization and duration of hospitalization was 2.22.4 days and 2.42.4 days respectively.There was a single episode of urinary tract infection and four subjects required re-catheterisation for non-hematuric retentions.Conclusions:This study supports the safety of men on NOACs undergoing PVP.Whilst this study represents the largest experience of PVP in these men,larger studies are necessary to confirm the safety of PVP in this group of men undergoing BPH-related surgery.展开更多
BACKGROUND Drug-induced liver injury(DILI)can be caused by any prescribed drug and is a significant reason for the withdrawal of newly launched drugs.Direct-acting oral anticoagulants(DOACs)are non-vitamin K-based ant...BACKGROUND Drug-induced liver injury(DILI)can be caused by any prescribed drug and is a significant reason for the withdrawal of newly launched drugs.Direct-acting oral anticoagulants(DOACs)are non-vitamin K-based antagonists recently introduced and increasingly used for various clinical conditions.A meta-analysis of 29 randomised controlled trials and 152116 patients reported no increased risk of DILI with DOACs.However,it is challenging to predict the risk factors for DILI in individual patients with exclusion of patients with pre-existing liver disease from these studies.AIM To determine the risk factors and outcomes of patients who developed DILI secondary to DOACs by systematic review and meta-summary of recent case reports and series.METHODS A systematic search was conducted on multiple databases including PubMed,Science Direct,Reference Citation Analysis,and Google Scholar.The search terms included“Acute Liver Failure”OR“Acute-On-Chronic Liver Failure”OR“Acute Chemical and Drug Induced Liver Injury”OR“Chronic Chemical and Drug Induced Liver Injury”AND“Factor Xa Inhibitors”OR“Dabigatran”OR“Rivaroxaban”OR“apixaban”OR“betrixaban”OR“edoxaban”OR“Otamixaban”.The results were filtered for literature published in English and on adult patients.Only case reports and case studies reporting cases of DILI secondary to DOACs were included.Data on demographics,comorbidities,medication history,laboratory investigations,imaging,histology,management,and outcomes were extracted.RESULTS A total of 15 studies(13 case reports and 2 case series)were included in the analysis,comprising 27 patients who developed DILI secondary to DOACs.Rivaroxaban was the most commonly implicated DOAC(n=20,74.1%).The mean time to onset of DILI was 40.6 d.The most common symptoms were jaundice(n=15,55.6%),malaise(n=9,33.3%),and vomiting(n=9,33.3%).Laboratory investigations showed elevated liver enzymes and bilirubin levels.Imaging studies and liver biopsies revealed features of acute hepatitis and cholestatic injury.Most patients had a favourable outcome,and only 1 patient(3.7%)died due to liver failure.CONCLUSION DOACs are increasingly used for various clinical conditions,and DILI secondary to DOACs is a rare but potentially serious complication.Prompt identification and cessation of the offending drug are crucial for the management of DILI.Most patients with DILI secondary to DOACs have a favourable outcome,but a small proportion may progress to liver failure and death.Further research,including post-marketing population-based studies,is needed to better understand the incidence and risk factors for DILI secondary to DOACs.展开更多
BACKGROUND Most of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation(AF)originated from western countrie...BACKGROUND Most of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation(AF)originated from western countries.AIM To systematically review and quantitatively synthesize the real-world data regarding the efficacy and safety of dabigatran,rivaroxaban,and apixaban compared to warfarin for stroke prevention in Asian patients with non-valvular AF.METHODS Medline,Cochrane,and ClinicalTrial.gov databases were reviewed.A randomeffect model meta-analysis was used and I-square was utilized to assess the heterogeneity.The primary outcome was ischemic stroke.The secondary outcomes were all-cause mortality,major bleeding,intracranial hemorrhage,and gastrointestinal bleeding.RESULTS Twelve studies from East Asia or Southeast Asia and 441450 patients were included.Dabigatran,rivaroxaban,and apixaban were associated with a significant reduction in the incidence of ischemic stroke[hazard ratio(HR)=0.78,95%confidence interval(CI):0.65-0.94;HR=0.79,95%CI:0.74-0.85,HR=0.70,95%CI:0.62-0.78;respectively],all-cause mortality(HR=0.68,95%CI:0.56-0.83;HR=0.66,95%CI:0.52-0.84;HR=0.66,95%CI:0.49-0.90;respectively),and major bleeding(HR=0.61,95%CI:0.54-0.69;HR=0.70,95%CI:0.54-0.90;HR=0.58,95%CI:0.43-0.78;respectively)compared to warfarin.CONCLUSION Dabigatran,rivaroxaban,and apixaban appear to be superior to warfarin in both efficacy and safety in Asians with non-valvular AF.展开更多
基金Supported by the Li Shu Fan Medical Foundation Professorship(to Leung WK)
文摘Novel oral anticoagulants(NOACs), which include direct thrombin inhibitor(dabigatran) and direct factor Xa inhibitors(rivaroxaban, apixaban and edoxaban), are gaining popularity in the prevention of embolic stroke in non-valvular atrial fibrillation as well as in the prevention and treatment of venous thromboembolism. However, similar to traditional anticoagulants, NOACs have the side effects of bleeding, including gastrointestinal bleeding(GIB). Results from both randomized clinical trials and observations studies suggest that high-dose dabigatran(150 mg b.i.d), rivaroxaban and high-dose edoxaban(60 mg daily) are associated with a higher risk of GIB compared with warfarin. Other risk factors of NOAC-related GIB include concomitant use of ulcerogenic agents, older age, renal impairment, Helicobacter pylori infection and a past history of GIB. Prevention of NOAC-related GIB includes proper patient selection, using a lower dose of certain NOACs and in patients with renal impairment, correction of modifiable risk factors, and prescription of gastroprotective agents. Overt GIB can be managed by withholding NOACs followed by delayed endoscopic treatment. In severe bleeding, additional measures include administration of activated charcoal, use of specific reversal agents such as idarucizumab for dabigatran and andexanent alfa for factor Xa inhibitors, and urgent endoscopic management.
文摘Objective:Photoselective vaporization of the prostate(PVP)is a widely performed surgical procedure for benign prostatic obstruction.This approach has become particular favoured for men on anti-platelet and anticoagulation agents such as clopidogrel and warfarin but there is minimal published experience in the setting of novel oral anticoagulants(NOACs).This study was to examine the perioperative outcomes in men on NOACs undergoing PVP,with particular reference to perioperative morbidity.Methods:A retrospective analysis of PVP datasets was undertaken from three centres in Sydney(Australia),Toulouse(France)and Boston(USA).Subjects who had been treated whilst on NOACs without discontinuation or bridging were identified.Perioperative outcomes and treatment parameters were examined and morbidity recorded according to Clavien-Dindo(CD)classification.Results:There were a total of 20 subjects who had undergone PVP whilst NOACs had been continued during the perioperative period.The mean age was 776.5 years.The mean prostate volume,energy utilization and vaporisation time was 9456 mL,301211 kJ,and 3521 min respectively.The mean postoperative duration of catheterization and duration of hospitalization was 2.22.4 days and 2.42.4 days respectively.There was a single episode of urinary tract infection and four subjects required re-catheterisation for non-hematuric retentions.Conclusions:This study supports the safety of men on NOACs undergoing PVP.Whilst this study represents the largest experience of PVP in these men,larger studies are necessary to confirm the safety of PVP in this group of men undergoing BPH-related surgery.
文摘BACKGROUND Drug-induced liver injury(DILI)can be caused by any prescribed drug and is a significant reason for the withdrawal of newly launched drugs.Direct-acting oral anticoagulants(DOACs)are non-vitamin K-based antagonists recently introduced and increasingly used for various clinical conditions.A meta-analysis of 29 randomised controlled trials and 152116 patients reported no increased risk of DILI with DOACs.However,it is challenging to predict the risk factors for DILI in individual patients with exclusion of patients with pre-existing liver disease from these studies.AIM To determine the risk factors and outcomes of patients who developed DILI secondary to DOACs by systematic review and meta-summary of recent case reports and series.METHODS A systematic search was conducted on multiple databases including PubMed,Science Direct,Reference Citation Analysis,and Google Scholar.The search terms included“Acute Liver Failure”OR“Acute-On-Chronic Liver Failure”OR“Acute Chemical and Drug Induced Liver Injury”OR“Chronic Chemical and Drug Induced Liver Injury”AND“Factor Xa Inhibitors”OR“Dabigatran”OR“Rivaroxaban”OR“apixaban”OR“betrixaban”OR“edoxaban”OR“Otamixaban”.The results were filtered for literature published in English and on adult patients.Only case reports and case studies reporting cases of DILI secondary to DOACs were included.Data on demographics,comorbidities,medication history,laboratory investigations,imaging,histology,management,and outcomes were extracted.RESULTS A total of 15 studies(13 case reports and 2 case series)were included in the analysis,comprising 27 patients who developed DILI secondary to DOACs.Rivaroxaban was the most commonly implicated DOAC(n=20,74.1%).The mean time to onset of DILI was 40.6 d.The most common symptoms were jaundice(n=15,55.6%),malaise(n=9,33.3%),and vomiting(n=9,33.3%).Laboratory investigations showed elevated liver enzymes and bilirubin levels.Imaging studies and liver biopsies revealed features of acute hepatitis and cholestatic injury.Most patients had a favourable outcome,and only 1 patient(3.7%)died due to liver failure.CONCLUSION DOACs are increasingly used for various clinical conditions,and DILI secondary to DOACs is a rare but potentially serious complication.Prompt identification and cessation of the offending drug are crucial for the management of DILI.Most patients with DILI secondary to DOACs have a favourable outcome,but a small proportion may progress to liver failure and death.Further research,including post-marketing population-based studies,is needed to better understand the incidence and risk factors for DILI secondary to DOACs.
文摘BACKGROUND Most of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation(AF)originated from western countries.AIM To systematically review and quantitatively synthesize the real-world data regarding the efficacy and safety of dabigatran,rivaroxaban,and apixaban compared to warfarin for stroke prevention in Asian patients with non-valvular AF.METHODS Medline,Cochrane,and ClinicalTrial.gov databases were reviewed.A randomeffect model meta-analysis was used and I-square was utilized to assess the heterogeneity.The primary outcome was ischemic stroke.The secondary outcomes were all-cause mortality,major bleeding,intracranial hemorrhage,and gastrointestinal bleeding.RESULTS Twelve studies from East Asia or Southeast Asia and 441450 patients were included.Dabigatran,rivaroxaban,and apixaban were associated with a significant reduction in the incidence of ischemic stroke[hazard ratio(HR)=0.78,95%confidence interval(CI):0.65-0.94;HR=0.79,95%CI:0.74-0.85,HR=0.70,95%CI:0.62-0.78;respectively],all-cause mortality(HR=0.68,95%CI:0.56-0.83;HR=0.66,95%CI:0.52-0.84;HR=0.66,95%CI:0.49-0.90;respectively),and major bleeding(HR=0.61,95%CI:0.54-0.69;HR=0.70,95%CI:0.54-0.90;HR=0.58,95%CI:0.43-0.78;respectively)compared to warfarin.CONCLUSION Dabigatran,rivaroxaban,and apixaban appear to be superior to warfarin in both efficacy and safety in Asians with non-valvular AF.