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Ken is 68 years old and has played the guitar in a band for over 15 years. Five years ago, Ken found himself having difficulty sleeping and urinating more frequently during the night. As these symptoms persisted, he began to lose his appetite and regularly found himself short of breath. After a visit to his doctor, urine and blood tests confirmed that Ken had abnormal kidney function with a creatinine clearance (CrCl) of 46 ml/min.
The band recently completed a national tour, travelling in a tour bus to more than 30 cities over 50 dates. Towards the end of the tour, Ken noticed that his right leg had become swollen and felt painful to the touch. Due to an extended period of immobility, he had developed a deep vein thrombosis (DVT).
What does the data tell us about treating patients with abnormal kidney function for acute venous thromboembolism (VTE)?
Guidelines suggest the use of non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) in patients with VTE for the first 3 months of treatment.1-3
Some patients are at greater risk of venous thromboembolic events and, therefore, require special attention. For example, patients who have moderately reduced kidney function (estimated glomerular filtration rate 30–60 ml/min/1.73 m2) are more than twice as likely to suffer a VTE than patients with normal kidney function.4 However, these patients can be challenging to treat because of their increased risk of bleeding during anticoagulation therapy.4-6
Vulnerable patients require guideline-recommended anticoagulation that has been thoroughly tested in patients like them. So how can you ensure that your vulnerable patients receive the validated protection that they deserve?
Phase III trials have investigated the efficacy and safety of NOACs for the treatment of acute VTE, but the patient populations were different in each trial.7-11 Across all NOAC VTE trials, the EINSTEIN programme recruited the greatest number of patients with CrCl 30–≤50 ml/min.9-12
Outcomes in patients with moderately impaired kidney function were reassuring. In a pre-specified pooled subgroup analysis of the EINSTEIN-DVT and EINSTEIN-PE studies, rivaroxaban was non-inferior to low molecular weight heparin (LMWH)/VKA for the treatment of DVT or PE and demonstrated protection from VTE recurrence across kidney function thresholds without increasing their risk of major bleeding compared with LMWH/VKA.12
Incidence of recurrent VTE and major bleeding across kidney function thresholds in the pooled analysis of EINSTEIN-DVT and EINSTEIN-PE trials.12
CrCl, creatinine clearance; LMWH, low molecular weight heparin; VKA, vitamin K antagonist; VTE, venous thromboembolism.
Furthermore, rivaroxaban was investigated in the prospective, international, non-interventional study, XALIA, which also included a high proportion of vulnerable patients.13 Notably, the consistent benefit in protection from recurrent VTE and major bleeding events with rivaroxaban was also observed in real-world practice in patients with DVT in XALIA.13
Efficacy and safety of rivaroxaban versus standard anticoagulation in patients with DVT or PE and moderately reduced GFR.12,13
Patients with CrCl 30–49 ml/min in EINSTEIN-DVT/EINSTEIN-PE and <50 ml/min in XALIA.
*LMWH followed by VKA in EINSTEIN-DVT/EINSTEIN-PE; UFH, LMWH or fondaparinux followed by VKA in XALIA.
#HR could not be calculated due to the low number of events.
CI, confidence interval; CrCl, creatinine clearance; GFR, glomerular filtration rate; HR, hazard ratio; LMWH, low molecular weight heparin; NR, not reported; RWE, real-world evidence; UFH, unfractionated heparin; VKA, vitamin K antagonist; VTE, venous thromboembolism.
The pooled analysis of EINSTEIN-PE and EINSTEIN-DVT also provided high quality evidence in fragile patients with VTE who are at high risk of recurrent events and major bleeding.14-16 Fragile patients were defined as patients with one or more of >75 years of age, CrCl <50 ml/min or low body weight (≤50 kg). Rivaroxaban-treated fragile patients had a significantly lower risk of major bleeding compared with patients treated with LMWH/VKA. Furthermore, a similar level of protection from recurrent VTE events was observed with rivaroxaban compared with LMWH/VKA irrespective of fragility.17
Incidence of recurrent VTE and major bleeding in fragile and non-fragile patients in the pooled analysis of the EINSTEIN-DVT and EINSTEIN-PE trials.17
*ITT population (N=8281); fragile patients (n=1573).
#One or more of: >75 years old, CrCl <50 ml/min, low body weight (≤50 kg).
‡Safety population (N=8246); fragile patients (n=1567).
ARR, absolute risk reduction; ITT, intention to treat; LMWH, low molecular weight heparin; RRR, relative risk reduction; VKA, vitamin K antagonist; VTE, venous thromboembolism.
Rivaroxaban has been thoroughly tested in patients with VTE and abnormal kidney function, like Ken. The EINSTEIN-DVT and EINSTEIN-PE pooled analysis and the real-world XALIA study have demonstrated a favourable efficacy profile for rivaroxaban across vulnerable patient subgroups, including fragile patients. The reassuring safety data from these studies suggest that you can be confident when treating patients whose comorbidities put them at an increased risk of major bleeding. So, when considering how to best protect your vulnerable patients from VTE recurrence, choose guideline-recommended protection that has a breadth of evidence in patients like them.