Atrial Fibrillation, Oral Anticoagulants, and Concomitant Active Cancer: Benefits and Risks.
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SUBMITTER: Atterman A
PROVIDER: S-EPMC8169314 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and aimsFew recent large-scale studies have evaluated the risks and benefits of continuing oral anticoagulant (OAC) therapy after catheter ablation (CA) for atrial fibrillation (AF). This study evaluated the status of continuation of OAC therapy and the association between continuation of OAC therapy and thromboembolic and bleeding events according to the CHADS2 score.MethodsThis retrospective study included data from the Japanese nationwide administrative claims database of patients who underwent CA for AF between April 2014 and March 2021. Patients without AF recurrence assessed by administrative data of the treatment modalities were divided into two groups according to continuation of OAC therapy 6 months after the index CA. The primary outcomes were thromboembolism and major bleeding after a landmark period of 6 months. After inverse probability of treatment weighting analysis, the association between OAC continuation and outcomes was determined according to the CHADS2 score.ResultsAmong 231 374 patients included, 69.7%, 21.6%, and 8.7% had CHADS2 scores of ≤1, 2, and ≥3, respectively. Of these, 71% continued OAC therapy at 6 months. The OAC continuation rate was higher in the high CHADS2 score group than that in the low CHADS2 score group. Among all patients, 2451 patients (0.55 per 100 person-years) had thromboembolism and 2367 (0.53 per 100 person-years) had major bleeding. In the CHADS2 score ≤1 group, the hazard ratio of the continued OAC group was 0.86 [95% confidence interval (CI): 0.74-1.01, P = .06] for thromboembolism and was 1.51 (95% CI: 1.27-1.80, P < .001) for major bleeding. In the CHADS2 score ≥3 group, the hazard ratio of the continued OAC group was 0.61 (95% CI: 0.46-0.82, P = .001) for thromboembolism and was 1.05 (95% CI: 0.71-1.56, P = 0.81) for major bleeding.ConclusionsThis observational study suggests that the benefits and risks of continuing OAC therapy after CA for AF differ based on the patient's CHADS2 score. The risk of major bleeding due to OAC continuation seems to outweigh the risk reduction of thromboembolism in patients with lower thromboembolic risk.
| S-EPMC10873714 | biostudies-literature
Project description:BackgroundPatients with cancer are more likely to develop nonvalvular atrial fibrillation (NVAF). Currently there are no definitive clinical trials or treatment guidelines for NVAF patients with concurrent cancer.ObjectivesThis subgroup analysis of the ARISTOPHANES study compared the risk of stroke/systemic embolism (stroke/SE) and major bleeding (MB) among NVAF patients with active cancer who were prescribed non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin.MethodsA retrospective observational study was conducted in NVAF patients with active cancer who newly initiated apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, through September 30, 2015, with the use of Medicare and 4 U.S. commercial claims databases. Cox models were used to estimate the risk of stroke/SE and MB in the pooled propensity score-matched cohorts.ResultsA total of 40,271 patients were included, with main cancer types of prostate (29%), female breast (17%), genitourinary (14%), and lung (13%). Compared with warfarin, apixaban was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.45-0.78) and MB (HR: 0.58; 95% CI: 0.50-0.68); dabigatran and rivaroxaban had similar risks of stroke/SE (dabigatran: HR: 0.88 [95% CI: 0.54-1.41]; rivaroxaban: HR: 0.82 [95% CI: 0.62-1.08]) and MB (dabigatran: HR: 0.76 [95% CI: 0.57-1.01]; rivaroxaban: HR: 0.95 [95% CI: 0.85-1.06]). Risks of stroke/SE and MB varied among NOAC-NOAC comparisons, while consistent treatment effects were seen for all treatment comparisons across key cancer types.ConclusionsAmong this cohort of NVAF patients with active cancer, the risk of stroke/SE and MB varied among oral anticoagulants and were consistent across cancer types.
| S-EPMC8463723 | biostudies-literature
Project description:Background and objectivesAll randomized trials of direct oral anticoagulants in atrial fibrillation excluded patients with severe kidney disease. The safety and effectiveness of direct oral anticoagulants across the range of eGFR in real-world settings is unknown. Our objective is to quantify the risk of bleeding and benefit of ischemic stroke prevention for direct oral anticoagulants compared with warfarin in patients with atrial fibrillation with and without CKD.Design, setting, participants, & measurementsWe created a propensity score-matched cohort of 3206 patients with atrial fibrillation and direct oral anticoagulant use and 3206 patients with atrial fibrillation using warfarin from October of 2010 to February of 2017 in an electronic health record (Geisinger Health System). The risks of bleeding and ischemic stroke were compared between direct oral anticoagulant and warfarin users using Cox proportional hazards regression, stratified by eGFR (?60 and <60 ml/min per 1.73 m2).ResultsThe mean (SD) age of the 6412 participants was 72 (12) years, 47% were women, and average eGFR was 69 (21) ml/min per 1.73 m2. There were 1181 bleeding events and 466 ischemic strokes over 7391 person-years of follow-up. Compared with warfarin use, the hazard ratios (HRs) (95% confidence interval [95% CI]) of bleeding associated with direct oral anticoagulant use were 1.01 (0.88 to 1.17) and 1.23 (1.02 to 1.48) for those with eGFR?60 and eGFR<60 ml/min per 1.73 m2, respectively (P-interaction=0.10). There was no difference between direct oral anticoagulant and warfarin users in the risk of ischemic stroke: HRs (95% CI) of 0.94 (0.74 to 1.18) and 1.02 (0.76 to 1.37) for those with eGFR?60 and eGFR<60 ml/min per 1.73 m2, respectively (P-interaction=0.70). Similar findings were observed with individual drugs.ConclusionsIn a large health care system, patients with eGFR<60 ml/min per 1.73 m2 who took direct oral anticoagulants for atrial fibrillation had slightly higher risk of bleeding compared with those on warfarin, but similar benefits from prevention of ischemic stroke.
| S-EPMC6086708 | biostudies-literature
Project description:Background Diltiazem, a moderate cytochrome P450 3A4 isozyme/P-glycoprotein inhibitor, may potentiate the bleeding risk of direct oral anticoagulants (DOACs) through pharmacokinetic interactions. We evaluated the association between concomitant use of diltiazem with DOACs and bleeding among patients with atrial fibrillation, across varying degrees of kidney function. Methods and Results We identified 4544 patients with atrial fibrillation who were initiated on rivaroxaban (n=1583), apixaban (n=2373), or dabigatran (n=588), between 2010 and 2019 in Geisinger Health, with a mean age of 72 years and an estimated glomerular filtration rate of 70 mL/min per 1.73 m2. At the time of DOAC initiation, 15% patients were taking diltiazem and an additional 5% were initiated on diltiazem during follow-up. Among DOAC users, using diltiazem concurrently (versus DOAC alone) was associated with an increased risk of any bleeding-related hospitalization (unadjusted risk difference, 2.4; 95% CI, 0.6-4.2 events per 100 person-years; adjusted hazard ratio, 1.56, 95% CI, 1.15-2.12), as well as major bleeding (unadjusted risk difference, 1.4 [95% CI, 0.1-2.6 events per 100 person-years]; adjusted hazard ratio, 1.84 [95% CI, 1.18-2.85]). Increased risk of any/major bleeding with diltiazem was observed in both patients with and without CKD (estimated glomerular filtration rate <60 mL/min per 1.73 m2) (P for interaction=0.524 and 0.629, respectively). Among 13 179 warfarin users (the negative control), concomitant diltiazem use was not associated with bleeding. Conclusions Concomitant use of diltiazem with DOACs was associated with a higher bleeding risk in patients with atrial fibrillation, consistently in both subgroups of chronic kidney disease and non-chronic kidney disease. For DOAC users, concomitant diltiazem should be prescribed only when the benefit outweighs the risk, with close monitoring for signs of bleeding.
| S-EPMC9707838 | biostudies-literature
Project description:The choice of an oral anticoagulant (OAC) for patients with nonvalvular atrial fibrillation (NVAF) is a major and complex clinical decision taking into account the individual risk-benefit ratio and bearing in mind the chronicity of therapy. This review focuses on the safety and efficacy of new oral anticoagulants (NOACs) compared with conventional vitamin K antagonists (VKA) in patients with NVAF. Current data suggest that NOACs are at least as effective and safe as VKAs for most NVAF subjects. The NOACs do not mandate dietary restrictions and regular pharmacodynamic monitoring, and they seem to have lesser incidence of intracranial or fatal bleeding when compared with VKAs. However, both dabigatran 150 twice daily and rivaroxaban have a slightly higher incidence of gastrointestinal bleeding when compared with VKAs. The article will delineate the current knowledge as well as scientific gaps related to the choice and dosage of anticoagulation regimens for various NVAF subsets and will address certain common clinical scenarios requiring special considerations. The article also addresses the shortcomings of NOACs: lack of therapeutic pharmacokinetic and pharmacodynamic targets, absence of tools to assess compliance and efficacy, rigid and limited dosage options, and absence of effective and inexpensive reversal agents.
| S-EPMC6490750 | biostudies-literature
Project description:Background Data on the effectiveness and safety of oral anticoagulant (OAC) agents in very elderly nonvalvular atrial fibrillation patients with high bleeding risk are lacking. Objectives This study examined 2-year outcomes and effects of OAC agents among these patients using the ANAFIE (All Nippon Atrial Fibrillation in the Elderly) registry (N = 32,275) data. Methods Patients were classified into high-risk (age: ≥80 years; CHADS2 score: ≥2; and presence of ≥1 bleeding risk factor: creatinine clearance of 15-30 mL/minute, prior bleeding at critical sites, body weight of ≤45 kg, or continuous antiplatelet use) and reference groups. Results In the high-risk (n = 7,104) and reference (n = 25,171) group patients, 89.0% and 93.4%, respectively, used OAC agents. Of these, respectively, 30.1% and 24.2% used warfarin, and 58.9% and 69.1% used direct-acting OAC (DOAC) agents. Compared with the reference group, the high-risk group had higher incidences of stroke/systemic embolism, major bleeding, intracranial hemorrhage, gastrointestinal bleeding, cardiovascular events, and all-cause death. In the high-risk group, DOAC agent use vs nonuse of OAC agents was associated with reduced incidences of stroke/systemic embolism (HR: 0.53; 95% CI: 0.36-0.79) and all-cause death (HR: 0.65; 95% CI: 0.52-0.81) but not with major bleeding (HR: 1.09; 95% CI: 0.63-1.89). DOAC agents were superior to warfarin in effectiveness and safety. For high-risk patients, history of major bleeding, severe liver dysfunction, and falls within 1 year were independent risk factors for major bleeding. Conclusions High-risk elderly nonvalvular atrial fibrillation patients had higher event incidences. DOAC agents were associated with reduced risk of stroke/systemic embolism and all-cause death vs nonuse of OAC agents or warfarin. (Prospective Observational Study in Late-Stage Elderly Patients With Nonvalvular Atrial Fibrillation [ANAFIE registry]; UMIN000024006) Central Illustration
| S-EPMC9700004 | biostudies-literature
Project description:BackgroundApproximately 20% of older persons with dementia have atrial fibrillation (AF). Nearly all have stroke risks that exceed the guideline-recommended threshold for anticoagulation. Although individuals with dementia develop profound impairments and die from the disease, little evidence exists to guide anticoagulant discontinuation, and almost one-third of nursing home residents with advanced dementia and AF remain anticoagulated in the last 6 months of life. We aimed to quantify the benefits and harms of anticoagulation in this population.MethodsUsing Minimum Data Set and Medicare claims, we conducted a retrospective cohort study with 14,877 long-stay nursing home residents aged ≥66 between 2013 and 2018 who had advanced dementia and AF. We excluded individuals with venous thromboembolism and valvular heart disease. We measured anticoagulant exposure quarterly, using Medicare Part D claims. The primary outcome was all-cause mortality; secondary outcomes were ischemic stroke and serious bleeding. We performed survival analyses with multivariable adjustment and inverse probability of treatment (IPT) weighting.ResultsIn the study sample, 72.0% were female, 82.7% were aged ≥80 years, and 13.5% were nonwhite. Mean CHA2 DS2 VASC score was 6.19 ± 1.58. In multivariable survival analysis, anticoagulation was associated with decreased risk of death (HR 0.71, 95% CI 0.67-0.75) and increased bleeding risk (HR 1.15, 95% CI 1.02-1.29); the association with stroke risk was not significant (HR 1.08, 95% CI 0.80-1.46). Results were similar in models with IPT weighting. While >50% of patients in both groups died within a year, median weighted survival was 76 days longer for anticoagulated individuals.ConclusionPersons with advanced dementia and AF derive clinically modest life prolongation from anticoagulation, at the cost of elevated risk of bleeding. The relevance of this benefit is unclear in a group with high dementia-related mortality and for whom the primary goal is often comfort.
| S-EPMC9957933 | biostudies-literature
Project description:Atrial fibrillation (AF) is the most prevalent clinically relevant arrhythmia, affecting millions of individuals in Europe and the USA. Atrial fibrillation increases the risk of stroke; the long-term standard of care for prevention of AF-related stroke is anticoagulation. The use of anticoagulants should be based on the absolute risks of stroke and bleeding and the relative benefit-risk profile of the individual patient. Treatment options include vitamin K antagonists (VKAs) such as warfarin, whose use is long-established but associated with drawbacks, including regular coagulation monitoring requirements and many food and drug interactions. The non-VKA oral anticoagulants are gaining widespread use as alternatives to VKAs, and are supported in treatment guidelines for patients with AF at moderate to high risk of stroke. Adherence to medication is important for the long-term efficacy of any therapy; however, relatively low levels of medication adherence are to be expected in 'real-world' AF patients compared with clinical trials. Experience across several therapy areas, including cardiovascular disease, shows that poor adherence to chronic medication is common. However, simple dosing schedules may be advantageous in this respect, and because long-term outcomes in AF are likely to be influenced by adherence, once-daily dosing has the potential to improve rates of stroke prevention in patients with AF.
| S-EPMC5421204 | biostudies-other
Project description:BackgroundStroke prevention is complicated in patients with atrial fibrillation (AF) and coronary artery disease (CAD). We compared the risk of major bleeding among Japanese patients with AF and CAD commencing warfarin, dabigatran, or rivaroxaban.MethodsThis study included adults with AF and CAD who were newly prescribed the non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran or rivaroxaban, or warfarin, and registered between 18 April 2011 through 31 December 2020 in the Medical Data Vision hospital-based clinical database. The primary outcome was major bleeding, and the secondary outcome was a composite of stroke, systemic embolism, myocardial infarction, all-cause inpatient mortality, major bleeding, major gastrointestinal bleeding, and intracerebral hemorrhage. Cox proportional hazard models with stabilized inverse probability treatment weighting were used to estimate hazard ratios (HRs) with 95 % CIs via a two-step approach; first between warfarin and each NOAC, then between NOACs if sample size conditions were met.ResultsDabigatran, rivaroxaban, and warfarin groups included 6712, 20,329, and 12,316 patients, respectively. Major bleeding risk was lower in NOACs versus warfarin (dabigatran: HR 0.50, 95 % CI: 0.40-0.62; rivaroxaban: HR 0.78, 95 % CI: 0.69-0.90); this risk was lower with dabigatran compared with rivaroxaban (HR 0.64, 95 % CI: 0.51─0.79). Net clinical benefit was superior to warfarin in both NOACs (dabigatran: HR 0.78, 95 % CI: 0.71-0.85; rivaroxaban: HR 0.83, 95 % CI: 0.78-0.88).ConclusionsAmong real-world Japanese patients with AF and CAD, NOACs were associated with better clinical outcomes than warfarin. Treatment with dabigatran had a lower risk of major bleeding than rivaroxaban.Clinical trial registration: NCT05051904 (ClinicalTrials.gov).
| S-EPMC10651495 | biostudies-literature
Project description:AimsAtrial fibrillation (AF) is a risk factor for brain infarction, which can lead to epilepsy. We aimed to investigate whether treatment of AF with direct oral anticoagulants (DOACs) affects the risk of epilepsy in comparison to treatment with the vitamin K antagonist phenprocoumon (PPC).Methods and resultsWe performed an active comparator, nested case-control study based on the German Pharmacoepidemiological Research Database that includes claims data from statutory health insurance providers of about 25 million persons since 2004. In 2011-17, 227 707 AF patients initiated treatment with a DOAC or PPC, of which 1828 cases developed epilepsy on current treatment with an oral anticoagulant. They were matched to 19 084 controls without epilepsy. Patients with DOAC treatment for AF had an overall higher risk of epilepsy with an odds ratio of 1.39, 95% CI (1.24; 1.55) compared to current PPC treatment. Cases had higher baseline CHA2DS2-VASc scores and more frequently a history of stroke than controls. After excluding patients with ischaemic stroke prior to the diagnosis of epilepsy, the risk of epilepsy was still higher on DOACs than on PPC. In contrast, within a cohort of patients with venous thromboembolism, the risk of epilepsy on treatment with DOACs was less elevated [adjusted odds ratio 1.15, 95% CI (0.98; 1.34)].ConclusionIn patients with AF initiating oral anticoagulation, treatment with a DOAC was associated with an increased risk of epilepsy compared to the vitamin K antagonist PPC. Covert brain infarction may explain the observed elevated risk of epilepsy.
| S-EPMC10228540 | biostudies-literature