Warfarin treatment quality and outcomes in patients with non-valvular atrial fibrillation and CKD G3-G5D.

INTRODUCTION: Warfarin treatment quality is calculated as time in therapeutic range (TTR). TTR ≥ 70 % is considered reducing the risk of adverse events for patients with atrial fibrillation (AF). The association of TTR and adverse events in chronic kidney disease (CKD) is however poorly investigated. The aim is to explore this further. MATERIALS AND METHODS: Swedish cohort study based on national healthcare registers between 2009 and 2018, including Swedish Renal Registry, Swedish Stroke Register and AuriculA - the Swedish national quality register for AF and anticoagulation. Investigating the effect of individual TTR (iTTR) and iTTR ≥ 70 % versus <70 % on the risk of ischemic stroke, major bleeding and death for patients with CKD GFR category 3-5 (G3-G5) including patients on dialysis (G5D) and non-valvular AF (NVAF). RESULTS: Of 2379 included patients 21.9 % had G3, 47.5 % G4, 10.8 % G5 and 19.8 % G5D. TTR in G3 was 75.6 %, G4 72.2 %, G5 67.6 % and G5D 62.0 %. Increase by 10 percentage points iTTR conferred lower risk of major bleeding, ischemic stroke and death for all patients (hazard ratio 0.91 (95 % Confidence interval 0.87-0.94), 0.92 (0.85-0.99) and 0.88 (0.85-0.90)). iTTR≥ 70 % versus <70 % was associated with lower risk of bleeding and death in all patients (0.63 (0.51-0.77) and (0.51 (0.43-0.61)), and a non-significant tendency towards lower stroke risk (0.67 (0.43-1.06)). CONCLUSIONS: Warfarin treatment quality worsens with decreasing GFR. Higher iTTR confers lower risk of bleeding, ischemic stroke and death in patients with NVAF and G3-G5D. iTTR ≥ 70 % was associated with better safety profile. Close monitoring of patients with CKD on warfarin is recommended.

Direct oral anticoagulants versus warfarin in patients with non-valvular atrial fibrillation and CKD G3-G5D.

Background: The use of direct oral anticoagulants (DOAC) in patients with non-valvular atrial fibrillation (NVAF) and advanced chronic kidney disease (CKD) including dialysis is growing. Several studies have shown favorable results of DOAC compared with warfarin regarding bleeding risk but no difference in stroke protection. However, these studies had poor time in therapeutic range (TTR), in the warfarin comparison group. Methods: This was a Swedish national cohort study investigating the risk of ischemic stroke and major bleeding on DOAC compared with warfarin in patients with NVAF, glomerular filtration rate category 3-5D (G3-G5D), kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality national healthcare registries including the Swedish Renal Registry, AuriculA (the Swedish national quality register for AF and anticoagulation) and The Stroke Register. Results: At enrolment, of 2453 patients 59% were treated with warfarin (mean TTR 67%) and 41% with DOAC. Overall, 693 (28.3%) had G3, 1113 (45.4%) G4, 222 (9.1%) G5 and 425 (17.3%) G5D. DOAC compared with warfarin showed lower hazard of major bleeding [hazard ratio 0.71 (95% confidence interval 0.53-0.96)] but no difference in ischemic stroke risk. Mortality was increased during DOAC treatment [1.24 (1.01-1.53)], presumably not a causal association since fewer fatal bleedings occurred on DOAC. Conclusions: DOAC treatment, compared with warfarin, is associated with almost 30% lower risk of bleeding in patients with NVAF and CKD G3-G5D. The stroke risk is comparable between the treatments. This is the first study comparing DOAC and well-managed warfarin (TTR 67%) in advanced CKD. Ongoing and planned randomized controlled trials need to confirm the possible benefit of DOAC.

Efficacy and safety of warfarin in patients with non-valvular atrial fibrillation and CKD G3-G5D.

Background: Observational data comparing warfarin with no treatment for patients with non-valvular atrial fibrillation (NVAF) and severely reduced glomerular filtration rate (GFR) are conflicting and randomized controlled trials (RCTs) are lacking. Most studies do not provide information on warfarin treatment quality, making them difficult to compare. Methods: This national cohort study investigates the risk of ischaemic stroke and major bleeding during warfarin treatment compared with no oral anticoagulants in patients with NVAF, GFR category 3-5 (G3-G5) or on dialysis (G5D), with kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality Swedish national healthcare registries, including the Swedish Renal Registry, AuriculA-the Swedish national quality registry for atrial fibrillation and anticoagulation-and the Stroke Registry. Results: At enrolment of 12 106 patients, 21.4% were G3, 43.5% were G4, 11.6% were G5 and 23.6% were G5D. The mean time in the therapeutic range was 70%. Warfarin compared with no treatment showed a lower risk for ischaemic stroke for G3 {hazard ratio [HR] 0.37 [95% confidence interval (CI) 0.18-0.76]}, G4 [0.53 (0.38-0.74)] and G5 [0.49 (0.30-0.79)] and an increased risk of major bleeding in G4 [HR 1.22 (1.02-1.46)], G5 [1.52 (1.15-2.01)] and G5D [1.23 (1.00-1.51)]. All-cause mortality was more than halved on warfarin compared with no treatment in all GFR categories. Conclusions: Warfarin treatment is associated with a lower risk of ischaemic stroke for patients with NVAF and G3, G4 and G5D at the cost of a higher risk of major bleeding for G4-G5D. Existing observational data are conflicting, stressing the need for RCTs on warfarin compared with no treatment in G4-G5D. Awaiting RCTs, it seems reasonable to treat selected patients on dialysis and NVAF with warfarin.

Prophylactic anticoagulants to prevent venous thromboembolism in patients with nephrotic syndrome-A retrospective observational study.

BACKGROUND: Nephrotic syndrome (NS) is associated with increased risk of venous thromboembolism (VTE). Guidelines suggest prophylactic anticoagulants to patients with high risk of thrombosis and low risk of bleeding, but the evidence behind this is poor. This study aims to investigate the effectiveness and risks of prophylactic anticoagulants (PAC) and investigate risk factors for VTE and bleeding in NS. METHODS: A retrospective medical records study including adults with NS, biopsy proven glomerular disease in the county of Västernorrland, Sweden. Outcomes were VTE, bleeding and death. Patients divided into PAC- and no PAC group were compared using Fisher's exact test. Patient time was divided into serum/plasma(S/P)-albumin intervals (<20g/L and ≥20g/L) and VTE- and bleeding rates were calculated. RESULTS: In 95 included NS patients (PAC = 40, no PAC = 55), 7 VTE (7.4%) and 17 bleedings (18%) were found. Outcomes didn't differ significantly between the PAC and no PAC group. Time with S/P-albumin <20g/L conferred higher rates/100 years of VTE (IRR 21.7 (95%CI 4.5-116.5)) and bleeding (IRR 5.0 (1.4-14.7)), compared to time with S/P-albumin>20g/L. CONCLUSION: Duration of severe hypoalbuminemia (S/P-albumin <20g/L) in NS is a risk factor for both VTE and bleeding. There is a need for randomized controlled studies regarding the benefit of PAC in NS as well as risk factors of thrombosis and bleeding in NS.

Serum levels of antibodies against oxidised LDL in kidney graft recipients.

BACKGROUND/AIMS: Lipid abnormalities present in the post-transplant period may contribute to the development and progression of complications leading to graft and patient loss. In the present study serum levels of antibodies against oxidised LDL (Ab-oxLDL) in kidney graft recipients were investigated along with their possible relation to the development of complications in the post-transplant period, and to the outcome of kidney transplantation. METHODS: Serum levels of Ab-oxLDL and lipid pattern were evaluated in 92 kidney graft recipients before and at 3, 6, 12, and 24 months after kidney transplantation, as well as in 90 healthy blood donors (control group). RESULTS: Kidney graft recipients had higher frequency of low levels of Ab-oxLDL as compared with the control group. A decrease in Ab-oxLDL levels was observed at 6 months post-transplant. Patients with early graft loss due to acute rejection had lower pre-transplant Ab-oxLDL levels (p < 0.05) as compared to patients with graft survival >3 months. CONCLUSIONS: It is suggested that decreased Ab-oxLDL levels found in kidney graft recipients may reflect impaired response to the products of lipid oxidation or increased consumption of Ab-oxLDL, and are associated with graft loss due to acute rejection.

Cardiovascular disease after renal transplantation.

Cardiovascular disease is a major hazard limiting the life expectancy of renal transplant recipients and the most frequent cause of late allograft loss. Patients with renal disease have usually been exposed for both traditional, and for them unique, risk factors over a prolonged period of time and may carry the burden of advanced atherosclerotic disease already at the time of transplantation. The observed survival benefit of transplantation is probably from elimination of the numerous uremia-related risk factors. However, immunosuppressive therapy and the chronic inflammatory state, together with genetic susceptibility and not infrequently impaired renal function, may bring about new potentially atherogenic conditions. Metabolic risk factors may jeopardize both patient and graft survival. Several observational studies provide evidence for the negative impact of preexisting metabolic abnormalities on long-term outcomes. Identification of modifiable cardiovascular risk factors may enable risk reduction also in renal transplant recipients. Results of ongoing intervention trials are awaited. The observed improvement of patient survival after renal transplantation during the past decade may reflect the increasing awareness and more optimal care of patients throughout the course of renal disease.