Paradoxical Procoagulant Effect of Early Doses of Warfarin: Possible Role of Non-Vitamin K Oral Anticoagulant in Patients with Atrial Fibrillation-Related Stroke.
Ontology highlight
ABSTRACT:
SUBMITTER: Kim Y
PROVIDER: S-EPMC4460341 | biostudies-literature | 2015 May
REPOSITORIES: biostudies-literature
Publications
Paradoxical Procoagulant Effect of Early Doses of Warfarin: Possible Role of Non-Vitamin K Oral Anticoagulant in Patients with Atrial Fibrillation-Related Stroke.
Journal of stroke 20150529 2
Similar Datasets
Project description:BackgroundSeveral studies have shown the cost-effectiveness of direct oral anticoagulants (DOACs), compared with warfarin, to prevent atrial fibrillation (AF) related complications. However, few have reported cost-effectiveness of DOACs in AF patients with intermediate stroke risk. Thus, we investigated the cost-effectiveness of DOACs vs. warfarin in non-valvular AF patients with intermediate stroke risk using national representative data.MethodsWe identified 7,954 newly diagnosed non-valvular AF patients (≥18 years) with intermediate stroke risk (CHA2DS2-VASc score: 1 for men and 2 for women) using the national healthcare utilization data from August 1, 2016, to July 31, 2019. Annual incidence rate of AF-related composite outcomes (heat failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, and gastrointestinal bleeding) was estimated. Cost-effectiveness was estimated using a Markov chain model with the transition probability of 1 year. The willingness-to-pay (WTP) was set at $32,000 per quality-adjusted life-year (QALY) gained.ResultsThe total cost of warfarin, rivaroxaban, apixaban, dabigatran and edoxaban was $2,874, $5,761, $5,151, $5,761 and $5,851, respectively. The QALYs gained were 10.83, 10.95, 11.10, 10.49 and 10.99 years, respectively. The incremental cost-effectiveness ratio of rivaroxaban, apixaban, dabigatran and edoxaban was $29,743.99, $8,426.71, -$8,483.04 and $18,483.55, respectively. The WTP was set at $32,000. DOACs (except dabigatran) were more cost-effective compared with warfarin because they did not exceed the WTP in the base-case analysis.ConclusionOur findings showed that DOACs were more cost-effective than warfarin in non-valvular AF patients with intermediate stroke risk.
| S-EPMC9035745 | biostudies-literature
Project description:Background Liver cirrhotic patients with nonvalvular atrial fibrillation have been excluded from randomized clinical studies regarding oral anticoagulants for stroke prevention. Whether non-vitamin K antagonist oral anticoagulants ( NOAC s) are superior to warfarin for these patients remains unclear. Methods and Results This nationwide retrospective cohort study, with data collected from the Taiwan National Health Insurance Research Database, enrolled 2428 liver cirrhotic patients with nonvalvular atrial fibrillation taking apixaban (n=171), dabigatran (n=535), rivaroxaban (n=732), or warfarin (n=990) from June 1, 2012, to December 31, 2016. We used propensity score-based stabilized weights to balance covariates across study groups. Patients were followed until the occurrence of an event or the end date of study. The NOAC group (n=1438) showed risk of ischemic stroke/systemic embolism and intracranial hemorrhage comparable to that of the warfarin group (n=990) after adjustment. The NOAC group showed significantly lower risk of gastrointestinal bleeding (hazard ratio: 0.51 [95% CI, 0.32-0.79]; P=0.0030) and all major bleeding (hazard ratio: 0.51 [95% CI, 0.32-0.74]; P=0.0003) compared with warfarin group. Overall, 90% (n=1290) of patients were taking a low-dose NOAC (apixaban 2.5 mg twice daily, rivaroxaban 10-15 mg daily, or dabigatran 110 mg twice daily). The subgroup analysis indicated that both dabigatran and rivaroxaban showed lower risk of all major bleeding than warfarin. The advantage of lower gastrointestinal and all major bleeding with NOACs over warfarin is contributed by those subgroups with either nonalcoholic or nonadvanced liver cirrhosis. Conclusions NOACs have a risk of thromboembolism comparable to that of warfarin and a lower risk of major bleeding among liver cirrhotic Asian patients with nonvalvular atrial fibrillation. Consequently, thromboprophylaxis with low-dose NOAC s may be considered for such patients.
| S-EPMC6474939 | biostudies-literature
Project description:Background Reduced time in international normalized ratio therapeutic range (TTR) limits warfarin safety and effectiveness. In patients switched from warfarin to direct oral anticoagulants (DOACs), patient factors associated with low TTR could also increase risk of DOAC nonadherence. We investigated the relationship between warfarin TTR and DOAC adherence in warfarin-treated patients with atrial fibrillation switched to DOAC. Methods and Results Using data from the Veterans Health Administration, we identified patients with atrial fibrillation switched from warfarin to DOAC (switchers) or treated with warfarin alone (non-switchers). Logistic regression was used to evaluate association between warfarin TTR and DOAC adherence. We analyzed 128 605 patients (age, 71±9; 1.6% women; CHA2DS2-VASc 3.5±1.6); 32 377 switchers and 96 228 non-switchers. In 8016 switchers with international normalized ratio data to calculate 180-day TTR before switch, TTR was low (median 0.45; IQR, 0.26-0.64). Patients with TTR <0.5 were more likely to be switched to DOAC (odds ratio [OR],1.68 [95% CI,1.62-1.74], P<0.0001), as were those with TTR <0.6 or TTR <0.7. Proportion of days covered ≥0.8 was achieved by 76% of switchers at 365 days. In low-TTR individuals, proportion of days covered ≥0.8 was achieved by 70%, 72%, and 73% of switchers with TTR <0.5, 0.6, and 0.7, respectively. After multivariable adjustment, TTR <0.5 decreased odds of achieving 365-day proportion of days covered ≥0.8 (OR, 0.49; 0.43-0.57, P<0.0001), with similar relationships for TTR <0.6 and TTR <0.7. In non-switchers with TTR <0.5, long-term TTR remained low. Conclusions In patients with atrial fibrillation switched from warfarin to DOAC, most achieved adequate DOAC adherence despite low pre-switch TTRs. However, TTR trajectories remained low in non-switchers. Patients with low warfarin TTR more consistently achieved treatment targets after switching to DOACs, although adherence-oriented interventions may be beneficial.
| S-EPMC9075386 | biostudies-literature
Project description:Atrial fibrillation (AF) is the most common cardiac arrhythmia in the developed world and is associated with a fivefold increase in the risk of stroke, accounting for up to 15% of strokes in the general population. The European Society of Cardiology now recommends direct oral anticoagulants, such as rivaroxaban, apixaban, and dabigatran, in preference to vitamin K antagonist therapy for the prevention of stroke in patients with A F. This review focuses on the direct Factor Xa inhibitor rivaroxaban, summarizing the properties that make rivaroxaban appropriate for anticoagulant therapy in this indication (including its predictable pharmacokinetic and pharmacodynamic profile and once-daily dosing regimen) and describing data from the Phase III ROCKET AF trial, which showed once-daily rivaroxaban to be noninferior to warfarin for the prevention of stroke in patients with nonvalvular AF. In this trial, similar rates of major and nonmajor clinically relevant bleeding were observed; however, when compared with warfarin, rivaroxaban was associated with clinically significant reductions in intracranial and fatal bleeding. On the basis of these results, rivaroxaban was approved in both the United States and the European Union for the prevention of stroke and systemic embolism in patients with nonvalvular AF. Subanalyses of ROCKET AF data showed rivaroxaban to have consistent efficacy and safety across a wide range of patients, and studies to confirm these results in real-world settings are underway. This review also describes practical considerations for treatment with rivaroxaban in clinical practice (including dose reductions in specific high-risk patients, eg, those with renal impairment), recommendations for the transition from vitamin K antagonists to rivaroxaban, the management of bleeding events, and the measurement of rivaroxaban exposure.
| S-EPMC3968084 | biostudies-other
Project description:BackgroundTo overcome the several drawbacks of warfarin, non-vitamin K antagonist oral anticoagulants (NOACs) were developed. Even though randomized controlled trials (RCTs) provided high-quality evidence, the real-world evidence is still needed. This systematic review and meta-analysis proposed to measure the safety and efficacy profile between warfarin and NOACs in non-valvular atrial fibrillation (NVAF) patients in preventing stroke.ResultsWe collected articles about the real-world studies comparing warfarin and NOACs for NVAF patients recorded in electronic scientific databases such as Embase, ProQuest, PubMed, and Cochrane. The pooled hazard ratio (HR) and 95% confidence interval (CI) were estimated using the generic inverse variance method. A total of 34 real-world studies, including 2287288 NVAF patients, were involved in this study. NOACs effectively reduced the stroke risk than warfarin (HR 0.77; 95% CI 0.69 to 0.87; p < 0.01). Moreover, NOACs effectively lowered all-cause mortality risk (HR 0.71; 95% CI 0.63 to 0.81; p < 0.01). From the safety aspect, compared to warfarin, NOACs significantly reduced major bleeding risk (HR 0.68; 95% CI 0.54 to 0.86; p < 0.01) and intracranial bleeding risk (HR 0.54; 95% CI 0.42 to 0.70; p < 0.01). However, NOACs administration failed to decrease gastrointestinal bleeding risk (HR 0.78; 95% CI 0.58 to 1.06; p = 0.12).ConclusionsIn NVAF patients, NOACs were found to be more effective than warfarin at reducing stroke risk. NOACSs also lowered the risk of all-cause mortality, cerebral hemorrhage, and severe bleeding in NVAF patients compared to warfarin.
| S-EPMC8357866 | biostudies-literature
Project description:BackgroundAtrial fibrillation detected after stroke (AFDAS) has a lower risk of ischemic stroke recurrence than known atrial fibrillation (KAF). While the benefit of oral anticoagulants (OAC) for preventing ischemic stroke recurrence in KAF is well established, their role in patients with AFDAS is more controversial. This study aimed to evaluate the association between OAC use and the risk of recurrent ischemic stroke in patients with AFDAS in a real-world setting.MethodsThis nationwide retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database. Patients hospitalized with a first-ever ischemic stroke and AFDAS confirmed within 30 days after hospitalization were assigned to OAC and non-OAC cohorts. Inverse probability of treatment weighting was applied to balance the baseline characteristics of the cohorts. The primary outcome was ischemic stroke recurrence. Secondary outcomes were intracranial hemorrhage (ICH), death, and the composite outcome of "ischemic stroke recurrence, ICH, or death." Multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI).ResultsA total of 4,508 hospitalized patients with stroke and AFDAS were identified. Based on OAC use, 2,856 and 1,652 patients were assigned to the OAC and non-OAC groups, respectively. During the follow-up period (median duration, 2.76 years), the OAC cohort exhibited a lower risk of ischemic stroke recurrence (aHR, 0.84; 95% CI, 0.70-0.99), death (aHR, 0.65; 95% CI, 0.58-0.73), and composite outcome (aHR, 0.70; 95% CI, 0.63-0.78) than did the non-OAC cohort. The risk of ICH (aHR, 0.96; 95% CI, 0.62-1.50) was not significantly different between the two cohorts.ConclusionOAC use in patients with AFDAS was associated with reduced risk of ischemic stroke recurrence, without an increased risk of ICH. This supports current guidelines recommending OACs for secondary stroke prevention in patients with AF, regardless of the time of diagnosis.
| S-EPMC9354040 | biostudies-literature
Project description:It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed. We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OACprior ) with those without prior oral anticoagulation (OACnaive ). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OACchanged ) with those who continued the same anticoagulation as secondary prevention (OACunchanged ). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine-Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71-84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2-12]). The median CHA2 DS2 -Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) was 5 (IQR = 4-6) and was similar for OACprior (n = 1,195) and OACnaive (n = 4,119, p = 0.103). During 6,128 patient-years of follow-up, 289 patients had AIS (4.7% per year, 95% CI = 4.2-5.3%). OACprior was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OACchanged (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OACunchanged (n = 585). Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA2 DS2 -Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high-risk patient group. ANN NEUROL 2020.
| S-EPMC7383617 | biostudies-literature
Project description:Background and purposeTo evaluate the outcome events and bleeding complications of the European Society of Cardiology (ESC) guideline-matched oral anticoagulant therapy for patients with acute ischemic stroke and atrial fibrillation (AF).MethodsPatients with acute ischemic stroke and AF from a nationwide multicenter registry (Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts [K-ATTENTION]) between January 2013 and December 2015 were included in the study. Patients were divided into the ESC guideline-matched and the non-matched groups. The primary outcome was recurrence of any stroke during the 90-day follow-up period. Secondary outcomes were major adverse cerebrovascular and cardiovascular events, ischemic stroke, intracranial hemorrhage, acute coronary syndrome, allcause mortality, and major hemorrhage. Propensity score matching and logistic regression analyses were performed to assess the effect of the treatments administered.ResultsAmong 2,321 eligible patients, 1,126 patients were 1:1 matched to the ESC guidelinematched and the non-matched groups. As compared with the non-matched group, the ESC guideline-matched group had a lower risk of any recurrent stroke (1.4% vs. 3.4%; odds ratio [OR], 0.41; 95% confidence interval [CI], 0.18 to 0.95). The risk of recurrent ischemic stroke was lower in the ESC guideline-matched group than in the non-matched group (0.9% vs. 2.7%; OR, 0.32; 95% CI, 0.11 to 0.88). There was no significant difference in the other secondary outcomes between the two groups.ConclusionsESC guideline-matched oral anticoagulant therapy was associated with reduced risks of any stroke and ischemic stroke as compared with the non-matched therapy.
| S-EPMC7900398 | biostudies-literature
Project description:BackgroundFor patients with atrial fibrillation who have an ischemic stroke or transient ischemic attack (TIA) despite taking direct oral anticoagulants (DOACs), the optimal strategy for ongoing anticoagulation is unknown.MethodsUsing provincial administrative databases in Alberta, Canada, we compared anticoagulant use before/after the breakthrough stroke/TIA and assessed recurrence of stroke/TIA or bleeding, with consideration of medication adherence. Adherence was defined as the proportion of days covered (PDC) being ≥ 80%.ResultsAmong 985 patients, the median age was 80 years (interquartile range 13), with a mean CHADS2 score of 1.7± 1 prior to the index event. Patients were followed for a median of 643 days (interquartile range 836). Following the index stroke/TIA event, 623 patients (63%) filled a prescription for the same DOAC regimen, 83 (8%) filled a prescription for a different dose, 155 (16%) switched DOAC agents, 51 (5%) switched to warfarin, and 73 (7%) filled no oral anticoagulant prescription. Patients who kept the same regimen more commonly had TIA index events (59%); patients who changed dose or drug more often had stroke index events (55%-78%). During follow-up, 135 (14%) had stroke/TIA recurrence, and 46 (5%) had bleeding; rates of each did not differ between prescribing patterns. Post-index event, the proportion of patients with a proportion of days covered ≥ 80% improved from 55% to 80%.ConclusionsAlthough most maintained the same DOAC regimen after stroke/TIA, rates of recurrent stroke/TIA and bleeding were similar across prescribing patterns. Stroke/TIA severity may have influenced prescribing practices. DOAC prescription adherence improved poststroke/TIA and signals an opportunity for optimization in patients with atrial fibrillation.
| S-EPMC10502439 | biostudies-literature
Project description:AimThe aim of this study was to establish whether non-vitamin K antagonist oral anticoagulants (NOACs) are superior to warfarin in preventing stroke recurrence for atrial fibrillation (AF) patients with an ischemic or hemorrhagic stroke at the baseline.MethodsFrom 1 January 2009 to 31 December 2017, stroke patients with AF treated with oral anticoagulants in the National Health Insurance Research Database in Taiwan were enrolled. The study was retrospective cohort design. Outcome measures were ischemic and hemorrhagic stroke recurrence. The Cox proportional hazard model was used to obtain the hazard ratio (HR).ResultsIn total, 39,840 stroke patients with AF treated with NOAC and 42,583 treated with warfarin were identified. NOACs were superior to warfarin in preventing all recurrent stroke [adjusted HR: 0.67, 95% confidence interval (CI), 0.63-0.71, p < 0.001]. Results for the ischemic stroke population were the same as that for all types for stroke (adjusted HR: 0.66, 95% CI, 0.62-0.70, p < 0.001). For the hemorrhagic stroke population, NOACs were equivalent to warfarin in preventing ischemic stroke (adjusted HR: 1.11, 95% CI, 0.86-0.43, p < 0.001), but NOACs were superior to warfarin in preventing hemorrhagic stroke (adjusted HR: 0.64, 95% CI, 0.55-0.74, p < 0.001).ConclusionsNOACs were generally superior to warfarin in terms of efficacy and safety in previous stroke patients. The robustness of our findings was verified and should add new information to current recommendations for Asian stroke patients in selecting NOACs.
| S-EPMC7705193 | biostudies-literature