John Hartemink

BACKGROUND: Patients with chronic kidney disease (CKD) have an increased risk of venous thromboembolism (VTE) and atrial fibrillation (AF). Anticoagulants have not been studied in randomised controlled trials with CrCl < 30 ml/min. The objective of this review was to identify the impact of different anticoagulant strategies in patients with advanced CKD including dialysis. METHODS: We conducted a systematic review of randomized controlled trials and cohort studies, searching electronic databases from 1946 to 2022. Studies that evaluated both thrombotic and bleeding outcomes with anticoagulant use in CrCl < 50 ml/min were included. RESULTS: Our initial search yielded 14,503 papers with 53 suitable for inclusion. RCTs comparing direct oral anticoagulants (DOACs) versus warfarin for patients with VTE and CrCl 30-50 ml/min found no difference in recurrent VTE events (RR 0.68(95% CI 0.42-1.11)) with reduced bleeding (RR 0.65 (95% CI 0.45-0.94)). Observational data in haemodialysis suggest lower risk of recurrent VTE and major bleeding with apixaban versus warfarin. Very few studies examining outcomes were available for therapeutic and prophylactic dose low molecular weight heparin for CrCl < 30 ml/min. Findings for patients with AF on dialysis were that warfarin or DOACs had a similar or higher risk of stroke compared to no anticoagulation. For patients with AF and CrCl < 30 ml/min not on dialysis, anticoagulation should be considered on an individual basis, with limited studies suggesting DOACs may have a preferable safety profile. CONCLUSION: Further studies are still required, some ongoing, in patients with advanced CKD (CrCl < 30 ml/min) to identify the safest and most effective treatment options for VTE and AF.

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Thromboembolic events (TEEs) are a serious and potentially fatal complication of nephrotic syndrome (NS). Despite this, there is a lack of evidence examining the benefits of prophylactic anticoagulation (PAC) in NS. It was our objective to review the risk factors, rates of TEEs, and patterns of PAC in patients with primary NS, with the aim to provide a pragmatic approach to PAC in primary NS. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; This is a retrospective longitudinal cohort study of adult patients with primary NS. Included were as follows: biopsy-proven minimal change disease and focal segmental glomerulosclerosis (described as a combined podocytopathy cohort) plus membranous nephropathy (MN) over an 8-year period from a single centre. Anticoagulation practice, TEEs, and longer term outcomes were recorded. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Fifty-four patients with MN and 48 patients with podocytopathies were included. Baseline demographics and severity of NS were comparable. Those with MN were more likely to develop TEE 12 (22%) versus 4 (8%) (&lt;i&gt;p&lt;/i&gt; = 0.027) though this difference was predominantly seen at index diagnosis. Only 2 patients developed TEEs during active incident NS. Rates of PAC were similar when comparing MN (53%) and podocytopathies (58%). Those with a serum albumin &amp;lt;20 g/L and HAS-BLED score &amp;lt;3 were most likely to receive PAC (22/30, 73% in MN vs. 21/30, 70% in podocytopathy). Warfarin was the most common agent used in MN cohort 18/26 (69%) versus prophylactic dose low-molecular-weight heparin in the podocytopathy cohort 12/28 (43%). &lt;b&gt;&lt;i&gt;Discussion/Conclusion:&lt;/i&gt;&lt;/b&gt; PAC practices applied in this cohort of patients were pragmatic and effective, with low TEE rates during active NS.

Abstract Background Early percutaneous coronary intervention (PCI) has a Class 1A recommendation for patients with non-ST elevation myocardial infarction (NSTEMI). However, the benefits of this invasive approach in patients with previous coronary artery bypass graft (CABG) surgery are uncertain, as these patients have previously been excluded from pivotal trials. Purpose We hypothesised that routine invasive management in patients with previous CABG presenting with NSTEMI, but otherwise medically stable, carried similar prognostic outcomes to patients who were medically managed. Methods This single centre retrospective observational study screened patients with prior CABG presenting with NSTEMI between January 2015 and December 2019. Patients either underwent coronary angiography with or without PCI at their physician's discretion or received standard acute coronary syndrome (ACS) medical therapy. Follow up time was 365 days from admission date, and clinical, demographic, procedural and outcome data were collected. The primary endpoint was major adverse cardiac events (MACE), a composite of all-cause mortality and rehospitalisation for unstable angina, myocardial infarction, or heart failure. Results The study included 267 patients (mean ±SD age: 72±10 years, 82% male), of whom 80.1% (N=214) underwent cardiac catheterisation, and 19.9% (N=53) only received standard ACS medical therapy. Amongst the invasive group, 65.4% (N=140) received PCI. No one was referred for re-do CABG. At 1-year follow up, the primary composite outcome occurred in 18 (13%) patients in the PCI group, 13 (18%) in those managed conservatively following angiography, and in 27 (51%) patients receiving medical therapy only. Cox regression modelling showed no significant difference in the 1-year primary endpoint amongst those having an angiogram who received PCI versus those treated medically after invasive assessment (HR: 0.75 [95% CI: 0.38–1.48; P=0.412]). Previous revascularisation with PCI (HR: 1.90 [CI, 1.11–3.24; P=0.018]) and chronic kidney disease (CKD) (HR: 2.60 [CI, 1.56–4.34; P&amp;lt;0.001]) at any stage, were the most important predictors of poor outcomes in CABG patients with NSTEMI irrespective of management strategy. Conclusion Patients with previous CABG who are admitted with NSTEMI who were not considered suitable for invasive angiography experienced significantly higher rates of MACE at 1-year follow up. The presence of CKD or previous PCI were key indicators of poor outcomes irrespective of management strategy. Outcomes amongst those deemed fit enough for invasive angiography were similar irrespective of treatment, suggesting that additional non-invasive testing may help further define which patients would benefit from an invasive strategy. Funding Acknowledgement Type of funding sources: None.

Abstract Background and Aims Patients who inject drugs (PWIDs) represent a uniquely difficult population to manage with haemodialysis, often with reliance on tunneled venous access. This population is historically difficult to reach, and their care is usually associated with higher per capita healthcare costs [1], unsurprisingly poor outcomes are reported [2] with a multitude of likely causes. Here we show the time associated opportunity costs these patients experience including the significant complication of tunnelled dialysis line infection in a person who actively injects drugs. Method This study follows on from the work by Burns [3]. In this retrospective observational study, the electronic health records of patients who were known to be ongoing users of recreational drugs were reviewed from January 2015 – August 2021. Patients were reviewed from their first tunneled line placement until either their death or until the end of the study time period. Stata 14 was used to generate descriptive statistics. Results 6 Patients were identified, 5 had a primary diagnosis of AA Amyloidosis with the other being IgA. This cohort of patients did poorly, 5 out of 6 of the cohort had died with a mean survival of 27 months. Patients were followed for an average of 769 days (range 485 - 1052). The majority of this time alive was spent as an inpatient with the mean percentage of time as an inpatient being 55% (Range 35–81%) with a mean of 411 total inpatient days. The first confirmed bacteraemia occurred within the first 100 days in 4 out of 6 of the patients. Conclusion With this case series we demonstrate the opportunity cost PWIDs experience in the form of time spent as an inpatient. This cost is further added to by the burden of outpatient maintenance haemodialysis. Consideration should also be given to the excess burden their care places on over-stretched healthcare systems. Infections and dialysis compliance are key components in the care of PWIDs and while moving away from tunneled access should be sought whenever possible a multidisciplinary approach should also be considered; these patients commonly lead chaotic lifestyles and in-center dialysis is usually the only option. Including addiction, social and psychiatric services alongside dialysis may be a way to engage with this historically difficult to reach population. The hope is that this study provides the incentive for further studies focusing on the opportunity costs and the quality of life this population can expect when embarking on haemodialysis. This would provide patients with realistic expectations while also aiding clinicians in navigating this difficult ethical situation.

BACKGROUND: Pre-emptive dose reduction of low-molecular-weight heparins (LMWHs) is often utilised in those with chronic kidney disease (CKD) to prevent bioaccumulation. We report on the association of a pre-emptive dose reduction on anti-Xa range and its correlation with clinical outcomes. METHODS: We undertook a retrospective service evaluation of patients with CKD (eGFR < 30 mL/min/1.73 m2) receiving therapeutic dose dalteparin. The primary exposure was dalteparin anti-Xa trough and peak. Primary outcomes were ISTH-defined clinically relevant bleeding, thrombosis, and all-cause mortality within 90 days of LMWH initiation. A multivariate Cox proportional hazards model was employed to assess the relationship between anti-Xa levels and the incidence of bleeding and mortality. RESULTS: A total of 103 patients were identified over a 2-year period. Seventy-eight (75.7%) had anti-Xa monitoring done. Trough anti-Xa distribution was within-target in 58 (75.6%). Patients on dialysis had a higher incidence of bleeding (19 vs. 12, p < 0.05). Patients with bleeding had significantly higher median anti-Xa trough (0.26 vs. 0.13 U/mL, p < 0.01). The median time to bioaccumulation was 19 days. In multivariate Cox models, only anti-Xa trough remained an independent association with bleeding (HR: 1.47 per 0.1 U/mL, 95% CI: 1.05-2.15; p < 0.05). No associations with mortality were identified. CONCLUSION: In this report, trough anti-Xa measurement of dalteparin is independently associated with bleeding in patients with CKD. Further prospective, larger studies are warranted to validate these results before it can be universally recommended in clinical practice.