Comparative safety of direct oral anticoagulants and warfarin in venous thromboembolism: multicentre, population based, observational study

Abstract

Objective To determine the safety of direct oral anticoagulant (DOAC) use compared with warfarin use for the treatment of venous thromboembolism. Design Retrospective matched cohort study conducted between 1 January 2009 and 31 March 2016. Setting Community based, using healthcare data from six jurisdictions in Canada and the United States. Participants 59 525 adults (12 489 DOAC users; 47 036 warfarin users) with a new diagnosis of venous thromboembolism and a prescription for a DOAC or warfarin within 30 days of diagnosis. Main outcome measures Outcomes included hospital admission or emergency department visit for major bleeding and all cause mortality within 90 days after starting treatment. Propensity score matching and shared frailty models were used to estimate adjusted hazard ratios of the outcomes comparing DOACs with warfarin. Analyses were conducted independently at each site, with meta-analytical methods used to estimate pooled hazard ratios across sites. Results Of the 59 525 participants, 1967 (3.3%) had a major bleed and 1029 (1.7%) died over a mean follow-up of 85.2 days. The risk of major bleeding was similar for DOAC compared with warfarin use (pooled hazard ratio 0.92, 95% confidence interval 0.82 to 1.03), with the overall direction of the association favouring DOAC use. No difference was found in the risk of death (pooled hazard ratio 0.99, 0.84 to 1.16) for DOACs compared with warfarin use. There was no evidence of heterogeneity across centres, between patients with and without chronic kidney disease, across age groups, or between male and female patients. Conclusions In this analysis of adults with incident venous thromboembolism, treatment with DOACs, compared with warfarin, was not associated with an increased risk of major bleeding or all cause mortality in the first 90 days of treatment. Trial registration Clinical trials NCT02833987.

Efficacy and safety of new direct oral anticoagulants in chronic kidney disease: AHA 2019 updated guidelines and review of the literature

“…Numerous studies have shown that DOACs significantly reduce the risk of embolism, strokes and intracranial bleeding events while increasing Gi bleeding compared to VKA use (Table iii) [20][21][22][23]. However, a study published by Jun et al did not show any association of Gi bleeding with the use of DOACs [24].…”

The use of direct oral anticoagulants in chronic kidney disease

“…Overall, they found similar efficacy for all DOACs in the prevention of recurrent VTE and a significant reduction in major bleeding; a finding which was consistent in those with moderate renal impairment (Van Es et al , ). Jun et al () undertook a real‐world observational study looking at the safety of DOACs versus warfarin within the first 90 days of VTE treatment. They looked at the subgroup of CKD, defined as an estimated GFR (eGFR) <60 ml/min/1·73 m 2 , and found no significant difference in major bleeding [HR 1·17(0·75–1·77)] or mortality [HR 0·68 (0·36–1·27)] however 95% of the patients on DOACs were prescribed rivaroxaban.…”

“…They looked at the subgroup of CKD, defined as an estimated GFR (eGFR) <60 ml/min/1·73 m 2 , and found no significant difference in major bleeding [HR 1·17(0·75–1·77)] or mortality [HR 0·68 (0·36–1·27)] however 95% of the patients on DOACs were prescribed rivaroxaban. So, this study is not necessarily representative of the DOACs as a class (Jun et al , ). Unfortunately, this study does not include information on VTE recurrence.…”

A synthetic heparin mimetic that allosterically inhibits factor XIa and reduces thrombosis in vivo without enhanced risk of bleeding

“…Yet, bleeding‐averse anticoagulation continues to be a significant challenge. While some reports suggest improvement in bleeding consequences with DOACs as compared to VKAs, others suggest no major improvement . Another challenge with DOACs is the difficulty of achieving rapid reversal in incidences of excessive bleeding.…”