Effectiveness and safety of direct oral anticoagulants in atrial fibrillation patients switched from vitamin K antagonists: A systematic review and meta‐analysis

A substantial proportion of atrial fibrillation patients initiating direct oral anticoagulants (DOAC) are vitamin K antagonists (VKA)‐experienced, for example switchers from VKA to DOAC. With this study, we aimed to summarize available evidence on the effectiveness and safety of DOAC vs VKA in real‐life VKA‐experienced atrial fibrillation patients. We searched EMBASE, MEDLINE and Cochrane Library systematically for English‐language studies indexed any time before October 2018. We included studies of VKA‐experienced atrial fibrillation patients initiating DOAC therapy, with continued VKA therapy as comparator. Outcomes included arterial thromboembolism and bleeding. When appropriate, meta‐analysis was performed by calculating pooled, weighted and adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Eight cohort studies comparing VKA‐experienced DOAC (dabigatran or rivaroxaban) users with continued VKA users were included. When comparing DOAC to VKA, an increased risk of ischaemic stroke and myocardial infarction was found for dabigatran (pooled aHR of 1.61 [95% CI 1.19‐2.19, I² = 65%] and 1.29 [95% CI 1.10‐1.52, I² = 0%], respectively), but not for rivaroxaban. The use of dabigatran in VKA‐experienced users was associated with an increased risk of gastrointestinal bleeding (pooled aHR 1.63 [95% CI 1.36‐1.94, I² = 30%]), but a decreased risk of intracranial bleeding (pooled aHR 0.45 [95% CI 0.32‐0.64, I² = 0%]). In conclusion, the use of dabigatran in prior VKA users in clinical practice was associated with a slightly increased risk of arterial thromboembolism and gastrointestinal bleeding, but a decreased risk of intracranial bleeding. Importantly, observational studies of real‐life VKA‐experienced oral anticoagulant users may be confounded by the reason for switching.     

Impact of methodological choices on a meta-analysis of real-world evidence comparing non-vitamin-K antagonist oral anticoagulants with vitamin K antagonists for the treatment of patients with non-valvular atrial fibrillation

Objective: The aim of this study was to investigate the impact of methodological choices in a meta-analysis of real-world evidence (RWE) comparing three non-vitamin-K antagonist oral anticoagulants with vitamin K antagonists (VKAs) for the treatment of patients with non-valvular atrial fibrillation (NVAF).

Methods: The meta-analysis was based on a systematic review of RWE studies enrolling incident and prevalent patients aged ≥18 years with NVAF and receiving either rivaroxaban, dabigatran, apixaban or a VKA. Five different scenarios were considered to explore the impact of the initial meta-analysis assumptions: (1) using studies that involved only incident patients; (2) excluding studies that only reported crude values and did not consider any adjustment; (3) including all studies independently of possible database overlap; (4) using studies with data on different dosages for rivaroxaban and dabigatran; and (5) assigning quality weights to studies to assess quality of reporting. These scenarios were run on three outcomes: ischemic stroke (IS), myocardial infarction (MI) and intracranial hemorrhage (ICH).

Results: Across all scenarios, rivaroxaban was associated with significantly lower risks of IS and ICH than VKAs. In most scenarios, dabigatran was associated with significantly lower risks of IS and ICH. In all scenarios, apixaban was associated with a significantly lower risk of ICH.

Conclusions: Sensitivity analyses showed the impact of similar assumptions was different depending on the outcome and the drug considered. The development of recommendations and guidelines for the inclusion of RWE in meta-analyses could prove useful in evaluating the effectiveness of health care interventions.     

Risk of stroke/systemic embolism,major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban,dabigatran or rivaroxaban compared with warfarin in the United States Medicare population

Objective: To compare the risk and cost of stroke/systemic embolism (SE) and major bleeding between each direct oral anticoagulant (DOAC) and warfarin among non-valvular atrial fibrillation (NVAF) patients.

Methods: Patients (≥65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Medicare database from 1 January 2013 to 31 December 2014. Patients initiating each DOAC were matched 1:1 to warfarin patients using propensity score matching to balance demographics and clinical characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major-bleeding-related medical costs between matched cohorts.

Results: Of the 186,132 eligible patients, 20,803 apixaban–warfarin pairs, 52,476 rivaroxaban–warfarin pairs, and 16,731 dabigatran–warfarin pairs were matched. Apixaban (hazard ratio [HR]?=?0.40; 95% confidence interval [CI] 0.31, 0.53) and rivaroxaban (HR?=?0.72; 95% CI 0.63, 0.83) were significantly associated with lower risk of stroke/SE compared to warfarin. Apixaban (HR?=?0.51; 95% CI 0.44, 0.58) and dabigatran (HR?=?0.79; 95% CI 0.69, 0.91) were significantly associated with lower risk of major bleeding; rivaroxaban (HR?=?1.17; 95% CI 1.10, 1.26) was significantly associated with higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban ($63 vs. $131) and rivaroxaban ($93 vs. $139) had significantly lower stroke/SE-related medical costs; apixaban ($292 vs. $529) and dabigatran ($369 vs. $450) had significantly lower major bleeding-related medical costs.

Conclusions: Among the DOACs in the study, only apixaban is associated with a significantly lower risk of stroke/SE and major bleeding and lower related medical costs compared to warfarin.     

Cost-effectiveness analysis of dabigatran versus rivaroxaban for stroke prevention in patients with non-valvular atrial fibrillation using real-world evidence in elderly US Medicare beneficiaries

Objective: Dabigatran and rivaroxaban have been approved by the US FDA to reduce the risk of stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) patients. Newly published real-world evidence based on the US population found that elderly Medicare patients with NVAF treated with rivaroxaban experienced statistically significant increases in intracranial hemorrhage (ICH) and major extracranial bleeding, and statistically nonsignificant decreases in thromboembolic stroke and acute myocardial infarction (AMI) compared with dabigatran. This study assessed the cost-effectiveness of dabigatran vs. rivaroxaban for the treatment of US Medicare NVAF patients.

Methods: A previously published Markov model was adapted to compare dabigatran and rivaroxaban. The model considered thromboembolic stroke, bleeding events, and AMI based on the published real-world event risks. Model outputs included clinical event rates, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs).

Results: Dabigatran patients experienced fewer ICH and major extracranial bleeding events than rivaroxaban patients, but more stroke and AMI events. Dabigatran was found to yield lower costs and higher QALYs than rivaroxaban, with incremental costs of ?$3534 and incremental QALYs of 0.004. Results remained consistent in sensitivity analyses, with a positive net monetary benefit (willingness-to-pay thresholds of $50,000 and $100,000 per QALY) for dabigatran over rivaroxaban for all model inputs tested.

Conclusions: In this study using US Medicare real-world data, dabigatran was found to dominate rivaroxaban. The analyses were limited by the short follow-up period of the real-world data and results may not be generalizable to other patient populations.     

利伐沙班与达比加群低剂量治疗非瓣膜性房颤患者有效性和安全性的Meta分析

目的:系统评价低剂量利伐沙班与达比加群在治疗非瓣膜性房颤患者中的有效性和安全性.方法:计算机检索中、英文数据库PubMed、EMBASE、Cochrane Library、MEDLINE、中国知网、万方、维普,收集低剂量利伐沙班与达比加群治疗非瓣膜性房颤有效性和安全性的队列研究,检索期限从建库至2021年8月.对符合纳入标准的研究进行资料提取和质量评价,采用Revman5.3软件进行统计学分析.结果:最终纳入了17篇研究.Meta分析结果显示:在有效性方面,利伐沙班与达比加群低剂量给药后卒中/全身性栓塞、心肌梗死发生率均无显著差异(P>0.05).在安全性方面,利伐沙班大出血、颅内出血、全因死亡风险均显著高于达比加群(P<0.05),而两组消化道出血风险无显著差异(P>0.05).亚组分析结果表明:欧洲和北美洲地区,两组卒中/全身性栓塞发生率无显著差异,利伐沙班大出血风险高于达比加群;亚洲地区,利伐沙班卒中/全身性栓塞发生率低于达比加群,但中国人群中两药无差异;两组大出血风险无显著差异.无论随访时间是否>1年,利伐沙班大出血风险均高于达比加群,且差异有统计学意义.结论:房颤患者超说明书低剂量给予达比加群的有效性与利伐沙班相似,而达比加群的安全性更高、死亡率更低;由于中国人群纳入的研究数过少,故该结论需谨慎对待.     

Educational Impact on Apixaban Adherence in Atrial Fibrillation (the AEGEAN STUDY): A Randomized Clinical Trial

Adherence to non-vitamin-K oral anticoagulants (NOACs) may be lower than to vitamin K antagonists because NOACs do not require routine monitoring. We assessed the impact of an educational program on adherence and persistence with apixaban in patients with non-valvular atrial fibrillation (NVAF). Patients with NVAF eligible for NOACs with one or more stroke risk factor (prior stroke/transient ischemic attack, age ≥ 75 years, hypertension, diabetes, or symptomatic heart failure) were randomized (1:1) to standard of care (SOC) or SOC with additional educational (information booklet, reminder tools, virtual clinic access). The primary outcome was adherence to apixaban (2.5 or 5 mg twice daily) at 24 weeks. Patients receiving the educational program were re-randomized (1:1) to continue the program for 24 further weeks or to switch to secondary SOC. Implementation adherence and persistence were reassessed at 48 weeks. In total, 1162 patients were randomized (SOC, 583; educational program, 579). Mean implementation adherence ± standard deviation (SD) at 24 weeks was 91.6% ± 17.1 for SOC and 91.9% ± 16.1 for the educational program arm; results did not differ significantly between groups at any time-point. At 48 weeks, implementation adherence was 90.4% ± 18.0, 90.1% ± 18.6, and 89.3% ± 18.1 for continued educational program, SOC, and secondary SOC, respectively; and corresponding persistence was 86.1% (95% confidence interval [CI] 81.3–89.7), 85.2% (95% CI 81.5–88.2), and 87.8% (95% CI 83.4–91.1). Serious adverse events were similar across groups. High implementation adherence and persistence with apixaban were observed in patients with NVAF receiving apixaban. The educational program did not show additional benefits. This study is registered at ClinicalTrials.gov [NCT01884350].     

An early evaluation of bleeding-related hospital readmissions among hospitalized patients with nonvalvular atrial fibrillation treated with direct oral anticoagulants

Objective:

Clinical trials have demonstrated that direct oral anticoagulants (DOACs) are efficacious in reducing stroke risk among patients with nonvalvular atrial fibrillation (NVAF) with differences in the reduction of bleeding risks vs. warfarin. The objective of this study was to assess bleeding-related hospital readmissions among hospitalized NVAF patients treated with dabigatran, rivaroxaban, and apixaban in the US.

Research design and methods:

Patients (≥18 years) with a discharge diagnosis of NVAF who received apixaban, dabigatran, or rivaroxaban during hospitalization were identified from the Premier Hospital database (1 January 2012–31 March 2014) and the Cerner Health Facts hospital database (1 January 2012–31 August 2014). Patients identified from each database were analyzed separately and grouped into three cohorts depending on which DOAC was received. Patient characteristics, hospital resource use and costs, and frequency of readmissions within 1 month were evaluated.

Results:

Among study populations identified from the Premier database (N?=?74,730) and the Cerner database (N?=?14,201), patients who received apixaban were older, had greater comorbidity, and had higher stroke and bleeding risks. After controlling for patient characteristics, including comorbidity and stroke and bleeding risks, compared with patients who received apixaban during their index hospitalizations, the odds of bleeding-related hospital readmissions were significantly greater by 1.4-fold (p?<?0.01) for patients who received rivaroxaban and 1.2-fold (p?=?0.16) numerically greater for patients who received dabigatran among patients identified from the Premier Hospital database. Among patients in the Cerner Health Facts hospital database, bleeding-related hospital readmissions were significantly greater by 1.6-fold (p?=?0.04) for patients who received rivaroxaban and 1.3-fold (p?=?0.30) numerically greater for patients who received dabigatran compared to patients who received apixaban.

Limitations:

No causal relationship between treatment and outcomes can be concluded.

Conclusions:

NVAF patients using different DOACs had different characteristics, including stroke and bleeding risks. Use of rivaroxaban, compared to apixaban was associated with significantly greater risk of bleeding-related readmissions across two database claims analyses.     

Changing anticoagulant paradigms for atrial fibrillation: dabigatran,apixaban and rivaroxaban

Introduction: Vitamin K antagonists (VKAs) are the main therapeutic agents used to prevent embolic events in patients with atrial fibrillation (AF). Despite their proven efficacy, VKAs are underused and have several limitations. In recent years, there has been great interest in the development of new oral anticoagulants with a more efficient pharmacological profile, first tested in venous thromboembolism prevention and later in AF.

Areas covered: The authors review the pharmacological differences between dabigatran, rivaroxaban and apixaban, and potential subgroups of patients in whom these new drugs would constitute a possible alternative to VKA therapy. Pharmacodynamic and pharmacokinetic data from each compound are analyzed in respect to their potential use in AF. This article provides an exhaustive review of the current status of this topic and the controversies still regarding each drug.

Expert opinion: Apixaban and rivaroxaban are under evaluation for thromboembolic prevention in AF; dabigatran was recently approved for this indication. Therefore, it is important to know the characteristics of these drugs as a potential alternative to VKAs.     

Changing anticoagulant paradigms for atrial fibrillation: dabigatran, apixaban and rivaroxaban

INTRODUCTION: Vitamin K antagonists (VKAs) are the main therapeutic agents used to prevent embolic events in patients with atrial fibrillation (AF). Despite their proven efficacy, VKAs are underused and have several limitations. In recent years, there has been great interest in the development of new oral anticoagulants with a more efficient pharmacological profile, first tested in venous thromboembolism prevention and later in AF. AREAS COVERED: The authors review the pharmacological differences between dabigatran, rivaroxaban and apixaban, and potential subgroups of patients in whom these new drugs would constitute a possible alternative to VKA therapy. Pharmacodynamic and pharmacokinetic data from each compound are analyzed in respect to their potential use in AF. This article provides an exhaustive review of the current status of this topic and the controversies still regarding each drug. EXPERT OPINION: Apixaban and rivaroxaban are under evaluation for thromboembolic prevention in AF; dabigatran was recently approved for this indication. Therefore, it is important to know the characteristics of these drugs as a potential alternative to VKAs.     

Comparative coronary risks of apixaban,rivaroxaban and dabigatran: a meta-analysis and adjusted indirect comparison

Aims

There are concerns regarding increased risk of acute coronary syndrome with dabigatran. We aimed to assess whether alternative treatment options such as rivaroxaban or apixaban carry a similar risk as compared with dabigatran.

Methods

We searched MEDLINE and EMBASE for randomized controlled trials of apixaban, dabigatran or rivaroxaban against control (placebo, heparin or vitamin K antagonist). We pooled odds ratios (OR) for adverse coronary events (acute coronary syndrome or myocardial infarction) using fixed effect meta-analysis and assessed heterogeneity with I². We conducted adjusted indirect comparisons to compare risk of adverse coronary events with apixaban or rivaroxaban vs. dabigatran.

Results

Twenty-seven randomized controlled trials met the inclusion criteria. Dabigatran was associated with a significantly increased risk of adverse coronary events in pooled analysis of nine trials (OR 1.45, 95% CI 1.14, 1.86). There was no signal for coronary risk with apixaban from nine trials (pooled OR 0.89, 95% CI 0.78, 1.03) or rivaroxaban from nine trials (pooled OR 0.81, 95% CI 0.72, 0.93). Overall, adjusted indirect comparison suggested that both apixaban (OR 0.61, 95% CI 0.44, 0.85) and rivaroxaban (OR 0.54; 95% CI 0.39, 0.76) were associated with lower coronary risk than dabigatran.Restricting the indirect comparison to a vitamin K antagonist as a common control, yielded similar findings, OR 0.57 (95% CI 0.39, 0.85) for apixaban vs. dabigatran and 0.53 (95% CI 0.37, 0.77) for rivaroxaban vs. dabigatran.

Conclusions

There are significant differences in the comparative safety of apixaban, rivaroxaban and dabigatran with regards to acute coronary adverse events.     

Heavy menstrual bleeding in women treated with rivaroxaban and vitamin K antagonists and the risk of recurrent venous thromboembolism

Anticoagulants increase the risk of heavy menstrual bleeding (HMB). We sought to investigate the incidence, predictors and management of HMB in women on rivaroxaban compared to those on vitamin K antagonists (VKA). We addressed the issue as to whether HMB is associated with VTE recurrences. We performed a single-center prospective study in menstruating women aged 18–55 years treated with rivaroxaban or VKA ≥ 3 months since the index VTE episode. Seventy six women on rivaroxaban and 45 patients on VKA were included. Patients on rivaroxaban more commonly reported HMB compared with those on VKA (31 [41%] vs. 8 [18%], p = 0.009). Women treated with rivaroxaban more frequently needed interventions to reduce menstruation compared with those on VKA (29 [38%] vs. 6 [13%], p = 0.004). During the median follow-up time of 13 months, there were 8 (11%) recurrent VTE on rivaroxaban and 3 (7%) on VKA (p = 0.5). Rivaroxaban treatment predisposed to HMB (odds ratio [OR] 3.2, 95% [confidence interval] CI 1.4–8.2, p = 0.007) and the interruption of anticoagulant treatment for 2–3 days (OR 3.2, 95% CI 1.1–11.6, p = 0.033). HMB during the rivaroxaban treatment predisposed to recurrent VTE (OR 5.3, 95% CI 1.1–33.3, p = 0.038). In menstruating women following VTE, rivaroxaban is associated with a two-fold higher risk of HMB compared with VKA. HMB predisposes to recurrent VTE episode, most likely due to the short interruptions of anticoagulation.     

Comparison of effectiveness and safety of treatment with apixaban vs. other oral anticoagulants among elderly nonvalvular atrial fibrillation patients

Objective: To compare the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) of elderly (≥65 years of age) nonvalvular atrial fibrillation (NVAF) patients initiating apixaban vs. rivaroxaban, dabigatran, or warfarin.

Methods: NVAF patients with Medicare Advantage coverage in the US initiating oral anticoagulants (OACs, index event) were identified from the Humana database (1 January 2013–30 September 2015) and grouped into cohorts depending on OAC initiated. Propensity score matching (PSM), 1:1, was conducted among patients treated with apixaban vs. each other OAC, separately. Rates of S/SE and MB were evaluated in the follow-up. Cox regressions were used to compare the risk of S/SE and MB between apixaban and each of the other OACs during the follow-up.

Results: The matched pairs of apixaban vs. rivaroxaban (n?=?13,620), apixaban vs. dabigatran (n?=?4654), and apixaban vs. warfarin (n?=?14,214) were well balanced for key patient characteristics. Adjusted risks for S/SE (hazard ratio [HR] vs. rivaroxaban: 0.72, p?=?.003; vs. warfarin: 0.65, p?p?p?p?=?.27) and MB (HR: 0.82, p?=?.23) of NVAF patients treated with apixaban vs. dabigatran trended to be lower, but did not reach statistical significance.

Conclusions: In the real-world setting after controlling for differences in patient characteristics, apixaban is associated with significantly lower risk of S/SE and MB than rivaroxaban and warfarin, and a trend towards better outcomes vs. dabigatran among elderly NVAF patients in the US.     

An update on the pharmaceutical management of thrombosis

Introduction: Anticoagulants such as heparins and vitamin K antagonists (VKA) are effective for thrombosis prevention and treatment, but are associated with the risk of bleeding and other limitations, spurring the search for improved drugs.

Areas covered: to evaluate the newer anticoagulants, focusing on those tested in phase III clinical trials such as direct oral anticoagulants (DOACs), antisense oligonucleotides (ASO) and warfarin analogues. DOACs such as dabigatran, rivaroxaban, apixaban and edoxaban are licensed for stroke prevention in atrial fibrillation and treatment of venous thromboembolism, dabigatran, rivaroxaban and apixaban for postoperative thromboprophylaxis in patients undergoing elective hip or knee arthroplasty and rivaroxaban for secondary prevention of acute coronary syndromes. ASO interfering with Factor XI hepatic synthesis were effective and safe for thromboprophylaxis in elective knee arthroplasty.

Expert opinion: DOACs have overcome some limitations of anticoagulants such as VKA, but are still associated with a risk of bleeding and they lack both standardized and widely available tests measuring their anticoagulant effect and a reversal agent, except for idarucizumab, specific for dabigatran, in case of major or life threatening bleeding or emergency surgery. Agents targeting Factor XI and possibly Factor XII may be ideal anticoagulants, as they can prevent thrombosis with low bleeding risk.     

A rapid evidence assessment of bleed-related healthcare resource utilization in publications reporting the use of direct oral anticoagulants for non-valvular atrial fibrillation

Objective: Non-valvular atrial fibrillation (NVAF), a common cardiac arrhythmia, is associated with high morbidity and carries a substantial economic burden. Historically, vitamin K antagonists (VKAs; e.g. warfarin) have been used for therapy of NVAF, but recently several direct oral anticoagulants (DOACs) have been approved for prevention of stroke in patients with NVAF. This review summarizes the real-world evidence (RWE) for healthcare resource utilization (HRU) in patients receiving oral anticoagulants (VKAs and/or DOACs) for therapy of NVAF.

Methods: A PRISMA-compliant literature search assessed Medline^® and Embase^® databases from 1 January 2011 to 4 May 2017, and the National Health Service Economic Evaluation Database from 1 January 2011 to 31 December 2015. Publications were included if they reported observational data from real-world use of one or more anticoagulant therapies. Outcomes of interest included hospitalizations, length of stay (LOS), mortality and costs.

Results: Twenty-eight publications were included. Apixaban and dabigatran were associated with fewer bleed-related hospitalizations than warfarin. Bleed-related LOS were generally longer for warfarin than for DOACs. Bleed-related treatment costs were lower for patients receiving apixaban or receiving dabigatran than patients receiving rivaroxaban or receiving warfarin. Bleed-related mortality in patients receiving oral anticoagulation for treatment of NVAF were low across all DOACs and warfarin.

Conclusions: The limited available evidence for HRU burden among patients receiving oral anticoagulation for NVAF suggests that DOACs (particularly apixaban and dabigatran) offer some degree of benefit in terms of HRU outcomes, compared with warfarin. Further work is required to understand HRU outcomes in patients receiving DOACs.     

Effectiveness and safety of rivaroxaban in nonvalvular atrial fibrillation: data from a contemporary Spanish registry

Objective: To ascertain the clinical profile, management and rates of thromboembolic and bleeding complications in a contemporary cohort of patients with nonvalvular atrial fibrillation (NVAF) on rivaroxaban treatment, with a particular focus on some subgroups of patients.

Methods: Retrospective study that included all NVAF patients who started treatment with rivaroxaban for the prevention of stroke or systemic embolism between December 2012 and December 2015. Rates of outcomes (stroke, nonfatal myocardial infarction, major bleeding, intracranial bleeding and death) during follow-up were calculated.

Results: A total of 732 patients (mean age 76.4?±?9.2?years; 54.5% women) were included. Comorbidities were common (hypertension 87.5%; diabetes 26.5%; renal insufficiency 24.6%; prior stroke/transient ischemic attack 16.8%). Mean CHA₂DS₂-VASc was 3.9?±?1.5 and HAS-BLED 2.3?±?0.9; 61.9% of patients were rivaroxaban naïve users. After a mean treatment period of 22.7?±?7.4?months, rates of stroke, nonfatal myocardial infarction, major bleeding, intracranial bleeding and death were 1.8, 1.0, 3.2, 0.4 and 5.5 events per 100 patient-years, respectively. Rates of stroke and death were higher in patients >75?years (vs. ≤75?years) and in patients with prior stroke/transient ischemic attack or renal insufficiency. Rates of major bleeding were higher among patients >75?years and in patients with prior stroke/transient ischemic attack.

Conclusions: In this contemporary Spanish cohort of NVAF patients on rivaroxaban, patients had many comorbidities, a high thromboembolic risk and a moderate bleeding risk. Overall, rates of stroke and bleeding complications were low and similar to other previous studies. These data suggest that rivaroxaban is effective and safe in routine practice.     

Safety of switching from vitamin K antagonists to dabigatran or rivaroxaban in daily care – results from the Dresden NOAC registry

Aim

Vitamin-K antagonists (VKA) and non-vitamin-K dependent oral anticoagulants (NOAC) have been approved for anticoagulation in venous thromboembolism (VTE) and atrial fibrillation and patients previously treated with VKA are switched to NOAC therapy. Safety data for this switching are urgently needed.

Methods

Using data from a large regional prospective registry of daily care NOAC patients, we evaluated the safety of switching anticoagulation from VKA to dabigatran or rivaroxaban. Switching procedures and cardiovascular and bleeding events occurring within 30 days after switching were centrally adjudicated.

Results

Between 1 October 2011 and 18 June 2013, 2231 patients were enrolled. Of these, 716 patients were switched from VKA to NOAC. Only 410 of the 546 evaluable patients (75.1%) had a recorded INR measurement within the 10 days preceding or following the end of VKA treatment (mean INR 2.4). As of day 30, major bleeding complications were rare (0.3%; 95% CI 0.0, 1.0) with an overall bleeding rate of 12.2% (95% CI 9.8, 14.8). Major cardiovascular events occurred in 0.8% (95% CI 0.3, 1.8). There was no significant difference in outcome event rates between the subgroups of patients with or without INR testing.

Conclusion

In daily care, only 75% of VKA patients have an INR measurement documented before NOAC are started. On average, NOAC are started within 2 to 5 days after the last intake of VKA. However, at 30 days follow-up cardiovascular events or major bleedings were rare both in patients with and without INR testing. However, switching procedures need to be further evaluated in larger cohorts of patients.     

Stroke risk reduction outweighed bleeding risk increase from vitamin K antagonist treatment among nonvalvular atrial fibrillation patients with high stroke risk and low bleeding risk

Objective: Warfarin is widely used for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). We compared the rates of stroke and major bleeding in NVAF patients with a high stroke risk and low bleeding risk profile during warfarin treated (W+) and warfarin untreated (W?) periods.

Method: Insurance claims from six commercial, Medicaid or Medicare databases were analyzed from 2000 to 2014. NVAF patients treated with warfarin, with a CHADS₂/CHA₂DS₂-VASc score ≥2, and an ATRIA score ≤3 at baseline were identified. Incidence rate ratios (IRRs) of stroke and major bleeding were calculated for W?+?versus W? episodes of person-time, as well as for first 30 days versus beyond 30 days of W?+?episodes.

Results: Among 316,145 patients, anticoagulant prophylaxis with warfarin significantly reduced stroke risk, with IRRs ranging from 0.48 (95% CI: 0.46–0.51) to 0.80 (95% CI: 0.70–0.91), and increased major bleeding risk, with IRRs ranging from 1.13 (95% CI: 1.10–1.15) to 1.95 (95% CI: 1.10–3.45). Stroke and major bleeding rates were higher during the first 30 days of W?+?than beyond.

Conclusion: In NVAF patients at high risk for stroke and low risk for bleeding, our data confirm the effectiveness of anticoagulation for stroke prevention. The decrease in stroke risk of anticoagulation may outweigh the risk of major bleeding events, particularly among elderly patients. Potential risks of warfarin during initiation warrant attention, especially among patients who stop and start therapy repeatedly.     

利伐沙班用于超高龄非瓣膜性房颤患者的安全性评价

目的:观察超高龄非瓣膜性房颤(non-valvular fibrillation,NVAF)患者临床特点和抗凝治疗安全性。方法:回顾性分析武汉市第三医院2020年5月至2021年4月接受利伐沙班抗凝治疗的NVAF患者,根据年龄分为观察组(年龄≥80岁)和对照组(<80岁)。观察2组患者发生缺血性脑卒中、心肌梗死、全身性栓塞、大出血及死亡事件的风险。结果:116人完成随访,观察组59人,对照组57人。所有患者至少合并1种慢性疾病,低体质量和肾功能不全是超高龄NVAF患者的生理特点。93.2%患者服用低于标准剂量的利伐沙班,52.5%患者有高或中等依从性。随访结束,2组患者缺血事件、大出血、临床相关非大出血和死亡事件的发生率相似。结论:对于超高龄NVAF患者应充分评估卒中风险和出血风险,低于标准剂量利伐沙班能否达到预期效果需进一步研究。