Prescription of Direct Oral Anticoagulants to Patients With Moderate-to-Advanced CKD: Too Little or Just Right?
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ABSTRACT:
SUBMITTER: Liabeuf S
PROVIDER: S-EPMC8418947 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background & aimsWhile direct oral anticoagulants (DOACs) are increasingly used in patients with liver disease, safety data especially in advanced chronic liver disease (ACLD) are limited.MethodsLiver disease patients receiving DOAC treatment (ACLD: n = 104; vascular liver disease: n = 29) or vitamin K antagonists (VKA)/low-molecular-weight heparin (LMWH; ACLD: n = 45; vascular: n = 13) between January 2010 and September 2020 were retrospectively included. Invasive procedures and bleeding events were recorded. Calibrated anti-Xa peak levels and thrombomodulin-modified thrombin generation assays (TM-TGAs) were measured in a subgroup of 35/28 DOAC patients.ResultsAmong patients receiving DOAC, 55 (41.3%) had advanced liver dysfunction (Child-Pugh-stage [CPS] B/C) and 66 (49.6%) had experienced decompensation. Overall, 205 procedures were performed in 60 patients and procedure-related bleedings occurred in 7 (11.7%) patients. Additionally, 38 (28.6%) patients experienced spontaneous (15 minor, 23 major) bleedings during a median follow-up of 10.5 (IQR: 4.0-27.8) months. Spontaneous bleedings in ACLD patients were more common in CPS-B/C (at 12 months: 36.9% vs CPS-A: 15.9%, subdistribution hazard ratio [SHR]: 3.23 [95% CI: 1.59-6.58], P < .001), as were major bleedings (at 12 months: 22.0% vs 5.0%, SHR: 5.82 [95% CI: 2.00-16.90], P < .001). Importantly, CPS (adjusted SHR: 4.12 [91% CI: 1.82-9.37], P < .001), but not the presence of hepatocellular carcinoma or varices, was independently associated with major bleeding during DOAC treatment. Additionally, ACLD patients experiencing bleeding had worse overall survival (at 12 months: 88.9% vs 95.0% without bleeding; P < .001). Edoxaban anti-Xa peak levels were higher in patients with CPS-B/C (345 [95% CI: 169-395] vs CPS-A: 137 [95% CI: 96-248] ng/mL, P = .048) and were associated with lower TM-TGA. Importantly, spontaneous bleeding rates were comparable to VKA/LMWH patients.ConclusionsAnticoagulants including DOACs should be used with caution in patients with advanced liver disease due to a significant rate of spontaneous bleeding events.
| S-EPMC8456813 | biostudies-literature
Project description:BackgroundThe 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.MethodsThis 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.ResultsAt 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.ConclusionsDOAC 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.
| S-EPMC10157779 | biostudies-literature
Project description:IntroductionPatients with chronic kidney disease (CKD) require multiple medications. There is no information on prescription patterns or the use of evidence-based therapies for management of CKD from low-middle-income countries. Using baseline data from the Indian CKD (ICKD) cohort, we describe the drug prescription practices in patients with mild to moderate CKD.MethodsThe ICKD study is a prospective, observational cohort study of mild to moderate kidney disease across 11 centers in India. We analyzed all the prescriptions captured at enrollment in the ICKD study. Drugs were categorized into 11 different groups. We provide descriptive data on prescription details and evaluate the appropriateness of medication use.ResultsComplete prescription data were available in 3966 out of 4056 (97.8%) subjects enrolled in the ICKD database. Most patients had stage 3 CKD, 24.9% had diabetic kidney disease, 87% had hypertension, and 25.5% had moderate to severe proteinuria. Renin-angiotensin-aldosterone system blockers were prescribed in less than half (47.9%) and in 58.8% of patients with proteinuric CKD. Metformin was prescribed in 25.7% of diabetic subjects with CKD. Only 40.4% of patients were taking statins; 31.1% and 2.8% subjects with anemia were receiving iron and erythropoiesis-stimulating agents, respectively.ConclusionThis study highlights the missed opportunities for improving outcomes through appropriate prescriptions of drugs in patients with CKD. There is need for dissemination of evidence-based guidelines and institution of sustainable implementation practices for improving the overall health of patients with CKD.
| S-EPMC8418981 | biostudies-literature
Project description:Direct oral anticoagulants (DOACs) have been licensed worldwide for several years for various indications. Each year, 10-15% of patients on oral anticoagulants will undergo an invasive procedure and expert groups have issued several guidelines on perioperative management in such situations. The perioperative guidelines have undergone numerous updates as clinical experience of emergency management has increased and perioperative studies including measurement of residual anticoagulant levels have been published. The high inter-patient variability of DOAC plasma levels has challenged the traditional recommendation that perioperative DOAC interruption should be based only on the elimination half-life of DOACs, especially before invasive procedures carrying a high risk of bleeding. Furthermore, recent publications have highlighted the potential danger of heparin bridging use when DOACs are stopped before an invasive procedure. As antidotes are progressively becoming available to manage severe bleeding or urgent procedures in patients on DOACs, accurate laboratory tests have become the standard to guide their administration and their actions need to be well understood by clinicians. This review aims to provide a systematic approach to managing patients on DOACs, based on recent updates of various perioperative guidance, and highlighting the advantages and limits of recommendations based on pharmacokinetic properties and laboratory tests.
| S-EPMC5433145 | biostudies-literature
Project description:ObjectivesTo describe the prevalence, temporal and regional trends in prescribing direct oral anticoagulants (DOACs) in conjunction with interacting medications.MethodsWe performed a cross-sectional study of pharmacy dispensing data in the Foundation for Pharmaceutical Statistics (SFK) registry on patients who have had a prescription for a DOAC filled at one of 831 randomly selected pharmacies in the Netherlands between Jan 2014-Jan 2019.ResultsWe identified 99,211 patients who had a first DOAC prescription filled. Mean age was 71.6 ± 10.9 years, 58% were male. In 2014, 8,293 patients were treated with DOACs, in 2018, 35,415 were newly started on a DOAC. In 2018, the use of apixaban was most common (52%) in the Eastern region, whereas rivaroxaban was most frequently prescribed (32-48%) in the other regions. At time of first prescription, the vast majority (99.3%) used ≥ 1 concomitant interacting drug, and 3.2% used ≥ 3 interacting medications. Most common were digoxin (37.8%), atorvastatin (31.5%), verapamil (13.7%) and amiodarone (9.7%). While the number of interacting medications remained unchanged over time (median 1, interquartile range 1-1), there was a notable decrease in antiarrhythmic medications and an increase in non-cardiovascular interacting medications (e.g. dexamethasone from 0.9% to 7.1%, antiepileptic drugs from 2.5% to 3.8%, and haloperidol from 0.5% to 2.2% in 2014 and 2018, respectively).ConclusionDOAC use has quadrupled in Dutch clinical practice over the 5‑year period from 2014 to 2018. While the number of patients who take interacting medications remained stable, the profile of interacting medications has changed over time from cardiovascular to medications affecting other organ systems.
| S-EPMC8397808 | biostudies-literature
Project description:Reversal agents for direct oral anticoagulants (DOACs), including factor X inhibitors and direct thrombin inhibitors, are a major concern in clinical practice. After DOACs were introduced and became widely used as an alternative for vitamin K antagonists in the management of venous thromboembolism and nonvalvular atrial fibrillation, the need for effective reversal agents has increased, particularly for life-threatening bleeding episodes related to DOACs or to reverse medication effects during urgent interventions. In the absence of specific reversal agents, prothrombin complex concentrate (PCC) and activated PCC are reasonable options to reverse bleeding associated with DOACs. However, high-quality clinical evidence is lacking. Idarucizumab is the only agent approved by the US Food and Drug Administration to reverse the effects of dabigatran; andexanet alfa and ciraparantag are also under evaluation as reversal agents for DOACs. This review summarizes the current evidence for nonspecific and specific reversal of DOACs.
| S-EPMC5529093 | biostudies-other
Project description:Direct oral anticoagulants (DOACs) are recognized by evidence-based treatment guidelines as the first-line option for the treatment of venous thromboembolism and prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. As use of these anticoagulants has become favored over the past several years, reported bleeding-related adverse drug events with these agents has increased. In randomized clinical trials, all DOACs have a reduced risk for intracranial hemorrhage, while major and other bleeding results have varied among the agents compared to vitamin K antagonists. We have reviewed the bleeding incidence and severity from randomized and real-world data in patients receiving DOACs in an effort to provide the clinician with a critical review of bleeding and offer practical considerations for avoiding adverse events with these anticoagulants.
| S-EPMC5574591 | biostudies-literature
Project description:Background: Geriatric conditions are common among patients with atrial fibrillation (AF) and relate to complications of oral anticoagulation (OAC). Objective: To examine the prevalence of geriatric conditions among older patients with AF on OAC and relate type of OAC to geriatric conditions. Methods: Participants had a diagnosis of AF, were aged ≥65 years, CHA2DS2VASC ≥ 2, and had no OAC contraindications. Participants completed a 6-component geriatric assessment that included validated measures of frailty (CHS Frailty Scale), cognitive function (MoCA), social support (MOS), depressive symptoms (PHQ9), vision, and hearing. Type of OAC prescribed was documented in medical records. Results: 86% of participants were prescribed an OAC. These participants were on average aged 75.7 (SD: 7.1) years, 49% were women, two thirds were frail or pre-frail, and 44% received a DOAC. DOAC users were younger, had lower CHA2DS2VASC and HAS-BLED scores, and were less likely to be frail. In Massachusetts, pre-frailty was associated with a significantly lower odds of DOAC vs. VKA use (OR = 0.64, 95%CI 0.45, 0.91). Pre-frailty (OR = 0.33, 95%CI 0.18-0.59) and social isolation (OR = 0.38, 95%CI 0.14-0.99) were associated with lower odds of DOAC receipt in patients aged 75 years or older. Social isolation was associated with higher odds of DOAC use (OR = 2.13, 95%CI 1.05-4.29) in patients aged 65-74 years. Conclusions: Geriatric conditions were common and related to type of OAC prescribed, differentially by age group. Research is needed to evaluate whether a geriatric examination can be used clinically to better inform OAC decision-making in older patients with AF.
| S-EPMC6831524 | biostudies-literature
Project description:A growing number of patients with an indication for stroke prevention in atrial fibrillation have kidney-, age-, or weight-related alterations in pharmacokinetics that affect dosing of direct oral anticoagulants. Because these patients were excluded from or comprised a small number of patients in clinical trials, there is a lack of evidence to guide clinicians. As a consequence, many patients do not receive oral anticoagulation despite a high risk for atrial fibrillation-related stroke. Here, we present a review of direct oral anticoagulant pharmacokinetics and a review of the available clinical evidence in patients with weight-, kidney-, and age-related disease.
| S-EPMC6490382 | biostudies-literature
Project description:Novel oral anticoagulants (NOACs) (rivaroxaban, dabigatran, apixaban) have been approved by international regulatory agencies to treat atrial fibrillation and venous thromboembolism in patients with kidney dysfunction. However, altered metabolism of these drugs in the setting of impaired kidney function may subject patients with CKD to alterations in their efficacy and a higher risk of bleeding. This article examined the efficacy and safety of the NOACs versus vitamin K antagonists (VKAs) for atrial fibrillation and venous thromboembolism in patients with CKD. A systematic review and meta-analyses of randomized controlled trials were conducted to estimate relative risk (RR) with 95% confidence interval (95% CIs) using a random-effects model. MEDLINE, Embase, and the Cochrane Library were searched to identify articles published up to March 2013. We selected published randomized controlled trials of NOACs compared with VKAs of at least 4 weeks' duration that enrolled patients with CKD (defined as creatinine clearance of 30-50 ml/min) and reported data on comparative efficacy and bleeding events. Eight randomized controlled trials were eligible. There was no significant difference in the primary efficacy outcomes of stroke and systemic thromboembolism (four trials, 9693 participants; RR, 0.64 [95% CI, 0.39 to 1.04]) and recurrent thromboembolism or thromboembolism-related death (four trials, 891 participants; RR, 0.97 [95% CI, 0.43 to 2.15]) with NOACs versus VKAs. The risk of major bleeding or the combined endpoint of major bleeding or clinically relevant nonmajor bleeding (primary safety outcome) (eight trials, 10,616 participants; RR 0.89 [95% CI, 0.68 to 1.16]) was similar between the groups. The use of NOACs in select patients with CKD demonstrates efficacy and safety similar to those with VKAs. Proactive postmarketing surveillance and further studies are pivotal to further define the rational use of these agents.
| S-EPMC3935586 | biostudies-literature