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Peripheral Artery Disease: causes and consequences

Coronary Artery Disease: causes and consequences

Patients with VTE and Renal Impairment

This section looks at the epidemiology of renal impairment in patients with VTE and examines how the presence of renal impairment affects prognosis and treatment with NOACs

Venous thromboembolism (VTE), which encompasses both deep vein thrombosis and pulmonary embolism (PE), is a common cause of morbidity and is the third most common cause of cardiovascular death after coronary heart disease and ischaemic stroke.1 Patients with VTE and renal impairment are at high risk of thrombotic events and require special attention.2 VTE and renal impairment frequently occur concomitantly.1 In the GARFIELD-VTE registry, approximately 46% of patients with established VTE had renal impairment; nearly 265.8% of patients with VTE had mild renal impairment (CrCl 60–89 ml/min) and approximately 20% had moderate-to-severe renal impairment (CrCl <60 ml/min).1

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Patients with VTE by level of renal function1

Patients with impaired renal function are often elderly, yet regardless of age, a decline in renal function has been shown to drastically increase the likelihood of a patient having a VTE.3,4 Those with severe renal impairment are five times more likely to suffer a venous thromboembolic event than those with normal renal function.

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The association between renal impairment and VTE3,4

The incidences of fatal PE and fatal bleeding are both increased greatly in patients with VTE who have renal insufficiency, with these risks increasing as renal function declines. Notably, there is a much higher likelihood of developing a fatal PE in patients with severe renal impairment than those who are immobile for more than 4 days.5

Several large, phase III trials investigated the efficacy and safety of non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) in patients with VTE, with the EINSTEIN DVT and EINSTEIN PE trials of rivaroxaban enrolling the highest proportion of patients with renal impairment.6-9

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Patients with renal impairment in the phase III NOAC VTE trials6-9

In the EINSTEIN PE and EINSTEIN DVT studies almost one-third of patients had renal impairment. In these studies, reassuringly, rivaroxaban demonstrated consistent efficacy compared with standard of care treatment (enoxaparin/VKA), regardless of the patient’s renal function. In patients with moderate renal impairment, rivaroxaban was associated with a significant 77% risk reduction in the risk of major bleeding, compared with enoxaparin/VKA.9
In the AMPLIFY trial, apixaban demonstrated a consistent treatment effect in those with or without renal impairment compared with enoxaparin/warfarin.6 In addition, the Hokusai-VTE trial showed that the protective effects of edoxaban in patients with VTE was unaffected by level of kidney function compared with warfarin.8 In contrast, in a post hoc subgroup analysis of the RE-COVER and RE-COVER II trials, the efficacy of dabigatran appeared to increase with renal impairment; this may have reflected an increase in dabigatran concentration as a result of reduced renal function.7
Overall, there is strong evidence to support the use of NOACs in patients with mild-to-moderate renal impairment and VTE. However, there are currently limited clinical data on patients with severe renal impairment, because this was an exclusion criterion in the aforementioned phase III studies of NOACs.6-8,10

The management of patients with VTE varies worldwide.1 However, both the European Society of Cardiology (ESC) guidelines and the American College of Chest Physicians (ACCP) recommend treatment with NOACs as a first-line therapy over the use of VKAs for the treatment of patients with VTE without a diagnosis of cancer.11,12 When considering the management of patients with VTE and renal impairment, the extent of renal decline may alter the recommended dosage and/or prescription of a NOAC. Rivaroxaban, edoxaban, apixaban and dabigatran are all excreted through the kidneys to some extent,13-16 and as a result may accumulate in patients with renal impairment. Careful dosing and close monitoring of renal function is recommended to avoid bleeding complications.17,18

See page on Anticoagulant Therapy for Venous Thromboembolism Prevention for more information on bleeding risk factors

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Renal excretion of the NOACs13-16

Recommendations by the ESC for the management of acute PE, which follow the respective dosing approved by the European Medicines Agency, do not advise the use of NOACs in patients with severe renal impairment (CrCl <15 ml/min). In patients with mild-to-moderate renal impairment, no dose adjustment is necessary with dabigatran, apixaban or rivaroxaban; however, a dose adjustment of edoxaban from 60 mg to 30 mg once daily in this population is recommended.12 For dabigatran, further label guidance states that for the primary prevention of VTE in orthopaedic surgery in patients with renal impairment (CrCl 30–50 ml/min), a reduced dose should be given.
The ESC concluded that based on currently available evidence from clinical trials, the optimal anticoagulant treatment(s) and regimen in patients with renal impairment and CrCl <30 ml/min remains unclear.12

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ESC recommendations for NOACs in patients with acute-phase treatment of intermediate- or low-risk PE and renal impairment

The CHEST Guideline and Expert Panel Report for Antithrombotic Therapy for VTE Disease provided further advice on anticoagulant treatment in patients with renal impairment. Anticoagulation with a VKA is preferred over NOACs or low molecular weight heparin in patients with renal disease and CrCl <30 ml/min, because NOACs and low molecular weight heparin are contraindicated these patients.11
Following a PE, patients taking anticoagulation therapies should undergo regular assessment of renal function, alongside hepatic function, drug tolerance and adherence, to assess if their risk of bleeding has increased.12


See page on Anticoagulant Therapy for Venous Thromboembolism Prevention


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