Clinical impact and course of major bleeding with rivaroxaban and vitamin K antagonists.
Rivaroxaban is a new oral anticoagulant (NOAC) that can be prescribed in a fixed dose, making regular monitoring and dose adjustments unnecessary. It has been proven to be safe and effective in comparison with enoxaparin/vitamin K antagonists (LMWH/VKA) for the (extended) treatment of venous thromboembolism in the EINSTEIN studies. Nevertheless, there is a need for information regarding the clinical impact of (major) bleeding events with NOACs such as rivaroxaban.
A post-hoc analysis was performed to compare the severity of clinical presentation and subsequent clinical course of major bleeding with rivaroxaban vs. LMWH/VKA.
Two investigators performed a blinded classification of major bleeding using a priori defined criteria. During the EINSTEIN studies, data concerning the clinical course and measures applied were prospectively collected for each major bleed.
Treatment with LMWH/VKA caused more major bleeding events (1.7%) than rivaroxaban (1.0%; hazard ratio, 0.54; 95% confidence interval [CI], 0.37-0.79). Major bleeding events during rivaroxaban therapy had a milder presentation (23% were adjudicated to the worst categories vs. 38% for LMWH/VKA; hazard ratio or HR, 0.35; 95% CI, 0.17-0.74; P = 0.0062). The clinical course was severe in 25% of all major bleeding events associated with rivaroxaban, compared with 33% of LMWH/VKA-associated bleeds (HR, 0.46; 95% CI, 0.22-0.96; P = 0.040).
Rivaroxaban-associated major bleeding events occurred less frequently, had a milder presentation and appeared to take a less severe clinical course compared with major bleeding with LMWH/VKA.
Eerenberg ES
，Middeldorp S
，Levi M
，Lensing AW
，Büller HR
... -
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Comparison of the short-term risk of bleeding and arterial thromboembolic events in nonvalvular atrial fibrillation patients newly treated with dabigatran or rivaroxaban versus vitamin K antagonists: a French nationwide propensity-matched cohort study.
The safety and effectiveness of non-vitamin K antagonist (VKA) oral anticoagulants, dabigatran or rivaroxaban, were compared with VKA in anticoagulant-naive patients with nonvalvular atrial fibrillation during the early phase of anticoagulant therapy.
With the use of the French medico-administrative databases (SNIIRAM and PMSI), this nationwide cohort study included patients with nonvalvular atrial fibrillation who initiated dabigatran or rivaroxaban between July and November 2012 or VKA between July and November 2011. Patients presenting a contraindication to oral anticoagulants were excluded. Dabigatran and rivaroxaban new users were matched to VKA new users by the use of 1:2 matching on the propensity score. Patients were followed for up to 90 days until outcome, death, loss to follow-up, or December 31 of the inclusion year. Hazard ratios of hospitalizations for bleeding and arterial thromboembolic events were estimated in an intent-to-treat analysis using Cox regression models. The population was composed of 19 713 VKA, 8443 dabigatran, and 4651 rivaroxaban new users. All dabigatran- and rivaroxaban-treated patients were matched to 16 014 and 9301 VKA-treated patients, respectively. Among dabigatran-, rivaroxaban-, and their VKA-matched-treated patients, 55 and 122 and 31 and 68 bleeding events and 33 and 58 and 12 and 28 arterial thromboembolic events were observed during follow-up, respectively. After matching, no statistically significant difference in bleeding (hazard ratio, 0.88; 95% confidence interval, 0.64-1.21) or thromboembolic (hazard ratio, 1.10; 95% confidence interval, 0.72-1.69) risk was observed between dabigatran and VKA new users. Bleeding (hazard ratio, 0.98; 95% confidence interval, 0.64-1.51) and ischemic (hazard ratio, 0.93; 95% confidence interval, 0.47-1.85) risks were comparable between rivaroxaban and VKA new users.
In this propensity-matched cohort study, our findings suggest that physicians should exercise caution when initiating either non-VKA oral anticoagulants or VKA in patients with nonvalvular atrial fibrillation.
Maura G
，Blotière PO
，Bouillon K
，Billionnet C
，Ricordeau P
，Alla F
，Zureik M
... -
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Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy.
Knee arthroscopy (KA) is a routine orthopedic procedure recommended to repair cruciate ligaments and meniscus injuries and in eligible patients, to assist the diagnosis of persistent knee pain. KA is associated with a small risk of thromboembolic events. This systematic review aims to assess if pharmacological or non-pharmacological interventions may reduce this risk. This review is the second update of the review first published in 2007.
To assess the efficacy and safety of interventions, whether mechanical, pharmacological, or in combination, for thromboprophylaxis in adult patients undergoing KA.
For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, the CENTRAL, MEDLINE, Embase and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries, on 14 August 2019.
We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs), whether blinded or not, of all types of interventions used to prevent deep vein thrombosis (DVT) in males and females aged 18 years and older undergoing KA. There were no restrictions on language or publication status.
Two authors independently selected studies for inclusion, assessed trial quality with the Cochrane 'Risk of bias' tool, and extracted data. A third author addressed discrepancies. We contacted study authors for additional information when required. We used GRADE to assess the certainty of the evidence.
This update adds four new studies, bringing the total of included studies to eight and involving 3818 adult participants with no history of thromboembolic disease undergoing KA. Studies compared daily subcutaneous (sc) low-molecular-weight heparin (LMWH) versus control (five studies); oral rivaroxaban 10 mg versus placebo (one study); daily sc LMWH versus graduated compression stockings (GCS) (one study); and aspirin versus control (one study). The incidence of pulmonary embolism (PE) in all trials combined was low, with seven cases in 3818 participants.There were no deaths in any of the intervention or control groups. LMWH versus control When compared with control, LMWH probably results in little to no difference in the incidence of PE in patients undergoing KA (risk ratio (RR) 1.81, 95% confidence interval (CI) 0.49 to 6.65; 1820 participants; 3 studies; moderate-certainty evidence). LMWH showed no reduction of the incidence of symptomatic DVT (RR 0.61, 95% CI 0.18 to 2.03; 1848 participants; 4 studies; moderate-certainty evidence). LMWH may reduce the risk of asymptomatic DVT but the evidence is very uncertain (RR 0.14, 95% CI 0.03 to 0.61; 369 participants; 2 studies; very low-certainty evidence). There was no evidence of an increased risk of all adverse events combined (RR 1.85, 95% CI 0.95 to 3.59; 1978 participants; 5 studies; moderate-certainty evidence). No evidence of a clear effect on major bleeding (RR 0.98, 95% CI 0.06 to 15.72; 1451 participants; 1 study; moderate-certainty evidence), or minor bleeding was observed (RR 1.79, 95% CI 0.84 to 3.84; 1978 participants; 5 studies; moderate-certainty evidence). Rivaroxaban versus placebo One study with 234 participants compared oral rivaroxaban 10 mg versus placebo. No evidence of a clear impact on the risk of PE (no events in either group), symptomatic DVT (RR 0.16, 95% CI 0.02 to 1.29; moderate-certainty evidence); or asymptomatic DVT (RR 0.95, 95% CI 0.06 to 15.01; very low-certainty evidence) was detected. Only bleeding adverse events were reported. No major bleeds occurred in either group and there was no evidence of differences in minor bleeding between the groups (RR 0.63, 95% CI 0.18 to 2.19; moderate-certainty evidence). Aspirin versus control One study compared aspirin with control. No PE, DVT or asymptomatic events were detected in either group. Adverse events including pain and swelling were reported but it was not clear what groups these were in. No bleeds were reported. LMWH versus GCS One study with 1317 participants compared the use of LMWH versus GCS. There was no clear difference in the risk of PE (RR 1.00, 95% CI 0.14 to 7.05; low-certainty evidence). LMWH use did reduce the risk of DVT compared to people using GCS (RR 0.17, 95% CI 0.04 to 0.75; low-certainty evidence). No clear difference in effects was seen between the groups for asymptomatic DVT (RR 0.47, 95% CI 0.21 to 1.09; very low-certainty evidence); major bleeding (RR 3.01, 95% CI 0.61 to 14.88; moderate-certainty evidence) or minor bleeding (RR 1.16, 95% CI 0.64 to 2.08; moderate-certainty evidence). Levels of thromboembolic events were higher in the GCS group than in any other group. We downgraded the certainty of the evidence for imprecision resulting from overall small event numbers; risk of bias due to concerns about lack of blinding, and indirectness as we were uncertain about the direct clinical relevance of asymptomatic DVT detection.
There is a small risk that healthy adult patients undergoing KA will develop venous thromboembolism (PE or DVT). There is moderate- to low-certainty evidence of no benefit from the use of LMWH, aspirin or rivaroxaban in reducing this small risk of PE or symptomatic DVT. There is very low-certainty evidence that LMWH use may reduce the risk of asymptomatic DVT when compared to no treatment but it is uncertain how this directly relates to incidence of DVT or PE in healthy patients. No evidence of differences in adverse events (including major and minor bleeding) was seen, but data relating to this were limited due to low numbers of events in the studies reporting within the comparisons.
Perrotta C
，Chahla J
，Badariotti G
，Ramos J
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《Cochrane Database of Systematic Reviews》
ResearchGate
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