Use Of Dabigatran Research Articles

Epistaxis and Dabigatran, a New Non-Vitamin K Antagonist Oral Anticoagulant

ObjectiveDabigatran is a new non-vitamin K antagonist (VKA) anticoagulant with anti-thrombin action, with supposedly fewer haemorrhagic complications. However, there are actually no established agents to reverse its effect, nor specific coagulation time tests for monitoring it. Materials and methodsAn observational prospective study was developed, noting epidemiological, clinical and therapeutic features among subjects with epistaxis treated with dabigatran. Results were compared with a group of epistaxis cases of individuals under anticoagulant therapy with VKA (acenocoumarol) and a control group without anticoagulation. ResultsSince its inclusion in our health system almost 3 years ago, 19 patients with epistaxis and concomitant use of dabigatran have been attended at the Emergency Unit in our hospital, as against 59 under VKA therapy and 144 without anticoagulation, with a mean admittance rate of 26%, 28%, and 14%, respectively. In 3 out of 5 individuals admitted due to dabigatran treatment, previously unobserved renal failure was detected. Blood transfusion was needed in 80% of patients using dabigatran, 58% using VKA, and 23% without anticoagulation. Invasive procedures to control nosebleed were required in 80%, 35%, and 21%, respectively. Although haemorrhagic risk was lower in dabigatran cases, they showed the longest stay in the hospital when compared to the other groups. ConclusionsWith dabigatran, there are fewer cases of severe epistaxis than with acenocoumarol, but controlling them is more difficult.

Bleeding incidence and real-life prescribing practices with dabigatran use in an acute care setting.

Since dabigatran's emergence in the United States market for use in preventing stroke and systemic embolism in nonvalvular atrial fibrillation, the Food and Drug Administration has issued two safety alerts for serious bleeding events. The postmarketing findings, along with anecdotal clinician concerns, prompted this drug utilization evaluation for dabigatran. We included all adult patients administered dabigatran from January 1, 2011, to December 31, 2011, while admitted to a large university-affiliated medical center. Dabigatran is available on formulary with a dosing and monitoring policy developed by a multidisciplinary subcommittee of the formulary and therapeutics committee. This is an institutional review board-approved retrospective chart review of 172 patients administered dabigatran during hospitalization. Incidence of gastrointestinal bleeds and minor bleeds with the use of dabigatran. The incidence of gastrointestinal bleeds in our study was 2.3% and minor bleeds was 2.3%. Doses outside of the manufacturer's recommendations were not associated with overt bleeds while in the hospital. Our results demonstrate that the incidence of bleeds experienced with dabigatran was relatively low despite the reports received by FDA.

Comparison of Outcomes After Cardioversion or Atrial Fibrillation Ablation in Patients With Differing Periprocedural Anticoagulation Regimens

BackgroundThere is a paucity of data that compare traditional vitamin K antagonist (VKA) with novel oral anticoagulant regimens in periprocedural management of cardioversion or ablation of atrial fibrillation (AF). We sought to compare outcomes of use of VKA, dabigatran (DABI), and rivaroxaban (RIVA) anticoagulation around the time of intervention. MethodsWe studied consecutive patients undergoing cardioversion or ablation of AF at our centre from October 2010 to October 2013. There were 3 different anticoagulation groups: warfarin (VKA), DABI, and RIVA. Safety was assessed according to number of strokes, transient ischemic attacks (TIAs), and clinically important and not important bleeding events. ResultsBaseline characteristics were well balanced between the groups. Average follow-up was 6 months (± 4 months). A total of 901 patients who underwent cardioversion were studied (VKA [n = 471], DABI [n = 288] and RIVA [n = 141]). In these patients there were no strokes seen during follow-up and 2 TIAs in the DABI group. Bleeding rates were low, with no significant difference between the 3 groups. A total of 680 patients who underwent ablation were studied (VKA [n = 319], DABI [n = 220] and RIVA [n = 171]). There were no strokes reported during follow-up and 3 TIAs: 2 in the VKA group and 1 in the DABI group not resulting in a significant difference between the groups. Bleeding rates were low, with no significant difference between the groups. ConclusionsOverall, there was a low incidence of adverse events for all anticoagulation regimens. Warfarin, DABI, and RIVA use around the time of the procedure are safe and reasonable options for patients who undergo cardioversion or AF ablation.

The use of dabigatran for prevention of ischemic stroke in patiets with atrial fibrillation: special features of treatment in different clinical situations

Atrial fibrillation (AF) is extremely highly prevalent both in Russia and in the world. Ischemic stroke is a severe complication of AF often resulting in disability or death. Therefore important role is given to conduct of primary and secondary prevention of development of thromboembolic complications which is realized by means of administration of antithrombotic therapy. For a long time warfarin has been used for this purpose. However compliance of physicians to its prescription remains unsatisfactory. Recently novel oral anticoagulants (NOAC) have been elaborated. Among them dabigatran has longest period of use and has been recommended as the drug of choice for patients with non-valvular AF. At present time wide use of dabigatran is limited because of lack of clear understanding of some practical questions of the use of this drug. Aim of this review--to analyze available data on efficacy and safety of dabigatran, to study special features of its administration in various clinical situations.

The peri-procedural use of dabigatran in patients undergoing left atrial ablation for atrial fibrillation.

Pulmonary vein isolation is an effective strategy in patients with atrial fibrillation (AF). The peri-procedural use of anticoagulation is routinely employed to reduce thromboembolic risk. The aim of this study was to compare the use of Dabigatran to the other 2 strategies involving the use of Warfarin. Single centre observational study comparing 3 anticoagulation strategies: Group 1 consisted of patients maintained on Warfarin (5.15±2.52mg) with a therapeutic INR of 2-3. Group 2 comprised patients initially treated with Warfarin (6.98±3.17mg), which was discontinued 1week prior to LA ablation, during which time patients were bridged with a therapeutic dose of Dalteparin. Group 3 included patients anticoagulated with Dabigatran (40 patients received 150mg BID, 3 patients received 110mg BID), which was discontinued 24-30h prior to the procedure. A total of 207 patients were included in the study. There were no significant differences in age, sex, LA volume, CHADS2 score or proportion of patients with persistent AF. There were no significant differences in the number of patients with intra-cardiac thrombus found at TOE (Group 1: 2.3% vs. Group 2: 1.5% vs. Group 3: 0%; P=0.37). Furthermore, there were no differences in the rate of groin hematoma (2.2% vs. 1.5% vs. 2.3%; P=0.8) or the development of pericardial effusion (5.4% vs. 8.8% vs. 2.3%; P=0.54). No thromboembolic events were seen. Peri-procedural use of Dabigatran during AF ablation procedures is safe, with no significant difference when compared to conventional anticoagulation with either Warfarin bridged with Dalteparin or uninterrupted Warfarin.

Estimated medical cost reductions associated with use of novel oral anticoagulants vs warfarin in a real-world non-valvular atrial fibrillation patient population

Objective:Results of randomized clinical trials (RCT) demonstrate that novel oral anticoagulants (NOAC) are effective therapies for reducing the risk of stroke in non-valvular atrial fibrillation (NVAF). Prior medical cost avoidance studies have used warfarin event rates from RCTs, which may differ from patients receiving treatment in a real-world (RW) setting, where the quality of care may not be the same as in a RCT. The purpose of this study was to estimate the change in medical costs related to stroke and major bleeding for each NOAC (apixaban, dabigatran, and rivoraxaban) relative to warfarin in a RW NVAF population.Methods:Patients (n = 23,525) with a diagnosis of NVAF during 2007–2010 were selected from a Medco population of US health plans. Stroke and major bleeding excluding intracranial hemorrhage (MBEIH) events were identified using diagnosis codes on medical claims. RW reference event rates were calculated during periods of warfarin exposure. RW event rates for NOACs were estimated by multiplying the corresponding relative risk (RR) from the RCTs by each reference rate. Absolute risk reductions (ARR) or number of events avoided per patient year were then estimated. Changes in medical costs associated with each NOAC were calculated by applying the ARR to the 1-year cost for each event. Costs for stroke and MBEIH were obtained from the literature. Drug and international normalized ratio monitoring costs were not considered in this analysis.Results:Compared to RW warfarin, use of apixaban and dabigatran resulted in total (stroke plus MBEIH) medical cost reductions of $1245 and $555, respectively, during a patient year. Rivaroxaban resulted in a medical cost increase of $144.Conclusions:If relative risk reductions demonstrated in RCTs persist in a RW setting, apixaban would confer the greatest medical cost savings vs warfarin, resulting from significantly lower rates of both stroke and MBEIH.

Bleeding Rates in Veterans Affairs Patients with Atrial Fibrillation Who Switch from Warfarin to Dabigatran

ObjectivesClinical trial data suggest that dabigatran and warfarin have similar rates of major bleeding but higher rates of gastrointestinal bleeding. These findings have not been evaluated outside of a clinical trial. We evaluated the relative risks of any, gastrointestinal, intracranial, and other bleeding for Veterans Affairs patients who switched to dabigatran after at least 6 months on warfarin, compared with patients who continued on warfarin. MethodsWe used national Veterans Affairs administrative encounter and pharmacy data from fiscal years 2010-2012 to identify 85,344 patients with atrial fibrillation who had been taking warfarin for at least 180 days before June 2011, of whom 1394 (1.7%) received dabigatran (150 mg) during the next 15 months. Dates of the first occurrence of each type of bleed and dates of death from June 2011 to September 2012 were determined. Baseline and time-dependent patient characteristics were identified, including comorbid conditions, stroke and bleeding risk scores, and time in therapeutic range for international normalized ratios. Marginal structural models were used to address selection bias in the longitudinal observational data. Weighted logistic regression models were fit using generalized estimating equations and reflected baseline and time-dependent covariates and weekly indicators of anticoagulant type (warfarin or dabigatran). ResultsCompared with patients who never used dabigatran, patients who used dabigatran at least once were younger, were more likely to be white, had lower international normalized ratio time in therapeutic range on warfarin, had lower stroke risk scores, and had similar bleeding risk scores. Overall, 10,734 patients experienced bleeding events, including 131 events after dabigatran use. The risk-adjusted rate of any bleeding was higher with dabigatran compared with warfarin, which was largely driven by a 54% higher risk of gastrointestinal bleeding with dabigatran. Rates of intracranial, other bleeding, and death were similar for dabigatran and warfarin. ConclusionsDabigatran may increase the likelihood of gastrointestinal bleeds.

Hearts aflutter: Atrial fib guidelines released

Hearts aflutter: Atrial fib guidelines released

Characteristics affecting oral anticoagulant therapy choice among patients with non-valvular atrial fibrillation: a retrospective claims analysis.

BackgroundDabigatran is one of the three newer oral anticoagulants (OACs) recently approved in the United States for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. The objective of this study was to identify patient, healthcare provider, and health plan factors associated with dabigatran versus warfarin use among NVAF patients.MethodsAdministrative claims data from patients with ≥2 NVAF medical claims in the HealthCore Integrated Research Database between 10/1/2009 and 10/31/2011 were analyzed. During the study intake period (10/1/2010 - 10/31/2011), dabigatran patients had ≥2 dabigatran prescriptions, warfarin patients had ≥2 warfarin and no dabigatran prescriptions, and the first oral anticoagulant (OAC) prescription date was the index date. Continuous enrollment for 12 months preceding (“pre-index”) and ≥ 6 months following the index date was required. Patients without pre-index warfarin use were assigned to the ‘OAC-naïve’ subgroup. Separate analyses were performed for ‘all-patient’ and ‘OAC-naïve’ cohorts. Multivariable logistic regression (LR) identified factors associated with dabigatran versus warfarin use.ResultsOf 20,320 patients (3,019 dabigatran and 17,301 warfarin) who met study criteria, 27% of dabigatran and 13% of warfarin patients were OAC-naïve. Among all-patients, dabigatran patients were younger (mean 67 versus 73 years, p < 0.001), predominantly male (71% versus 61%, p < 0.001), and more frequently had a cardiologist prescriber (51% versus 30%, p < 0.001) than warfarin patients. Warfarin patients had higher pre-index Elixhauser Comorbidity Index (mean: 4.3 versus 4.0, p < 0.001) and higher ATRIA bleeding risk score (mean: 3.0 versus 2.3, p < 0.001). LR results were generally consistent between all- and OAC-naïve patients. Among OAC-naïve patients, strongest factors associated with dabigatran use were prescriber specialty (OR = 3.59, 95% CI 2.68-4.81 for cardiologist; OR = 2.22, 95% CI 1.65-2.97 for other specialist), health plan type (OR = 1.47 95% CI 1.10-1.96 for preferred provider organization), and prior ischemic stroke (OR = 1.42, 95% CI 1.06-1.90). Older age decreased the probability of dabigatran use.ConclusionsBeside patient characteristics, cardiology specialty of the prescribing physician and health plan type were the strongest factors associated with dabigatran use.

Abstract 169: The Role Of Clinical Prediction Factors On Anticoagulant Selection In Atrial Fibrillation

Background: Atrial fibrillation (AF) often benefits from the use of anticoagulants for prevention of stroke or systemic embolism. While novel oral anticoagulants have emerged as possible alternatives to warfarin, it is unknown how treatment selection is determined in practice with clinical guidelines still evolving. This study examined whether and to what extent anticoagulant selection has been driven by clinical predictions of stroke risk (treatment benefit) and bleeding risk (treatment harm) in real-world practice in the US. Methods: A nationwide database of commercial and Medicare Part D supplement claims from 2009-2011 was used to extract a cohort of non-valvular AF patients who were newly-initiating therapy after dabigatran availability in Oct 2010. Patients were excluded if they had claims associated with a reversible AF condition. Risk scores of ischemic stroke (CHADS2 and CHA2DS2-VASc) and bleeding (ATRIA) were used to examine associations with either warfarin or dabigatran use, calculated via claims in the outpatient pharmaceutical, inpatient medical, outpatient, and provider claims files. Baseline demographic and clinical characteristics were also measured as covariates, including concomitant diseases and medications. Multivariable log-binomial regression models assessed the association between each risk score and anticoagulant use, adjusting for the measured covariates. C-statistics were also used to examine the variation in treatment selection explained by inclusion of the risk scores. Results: In total, 37,401 patients were identified with 31% initiating dabigatran. New users of dabigatran were more likely to be younger, male, and have comorbidities. Patients at intermediate stroke risk (CHADS2 or CHA2DS2-VASc =1) were equally likely to receive warfarin and dabigatran (RR, 95% CI: 0.98, 0.93-1.02), while selection for warfarin was significantly associated with high ischemic stroke risk (CHADS2 or CHA2DS2-VASc ≥2) (RR, 95% CI: 0.87, 0.83-0.92). New users of dabigatran were significantly less likely to have high bleeding risk (ATRIA≥5) versus warfarin (RR, 95%: 0.70, 0.66-0.74). The c-statistic of the base model, which included the other measured covariates, was only marginally increased with the addition of any of the risk scores. Conclusions: Despite controlling for other patient characteristics, bleeding risk was strongly associated with the selection of a specific anticoagulant. However, the extent of selection explained by predictions of treatment harm was minimal. Providers appear to base anticoagulant selection on factors other than predictions of treatment benefit, which has implications for studying the anticoagulants’ comparative effectiveness.

The Rate Of Complications Associated With Concomitant Use Of Dabigatran With Cryoballoon Ablation For Atrial Fibrillation.

Catheter ablation is an evolving therapeutic strategy for the management of atrial fibrillation (AF). It is associated with a risk of thromboembolic events. The peri-procedural anticoagulation management with warfarin has been successful in mitigating this risk. However, introduction of novel oral anticoagulants like dabigatran offers more flexibility in anticoagulation approaches. Previous studies had evaluated the safety and efficacy of dabigatran in the radiofrequency ablation, but data related to cryoballoon ablation is lacking. We performed a retrospective observational study involving patients who underwent cryoballoon ablation for drug-refractory, symptomatic AF while on dabigatran in periprocedural period. Thromboembolic, hemorrhagic or other complications occurring within the first 30 days after the ablation procedure were analyzed. Our study population comprised of 50 patients with mean age of 58.96 ± 3.54 years with 76% (n=38) being male. We found 3 (6%) minor complications in peri-procedural period including 2 groin hematomas and 1 trace asymptomatic pericardial effusion. There were no major intraprocedural or post procedural hemorrhagic or thromboembolic events. None of patients with the minor complications required significant additional workup or extended hospital stay. All the patients were able to continue dabigatran for 30 days without any additional side effects or complications. Dabigatran is a safe and efficacious agent in patients undergoing cryoballoon AF ablation.

Epistaxis y dabigatrán, nuevo anticoagulante oral no antagonista de la vitamina K

ObjectiveDabigatran is a new non-vitamin K antagonist (VKA) anticoagulant with anti-thrombin action, with supposedly fewer haemorrhagic complications. However, there are actually no established agents to reverse its effect, nor specific coagulation time tests for monitoring it. Materials and methodsAn observational prospective study was developed, noting epidemiological, clinical and therapeutic features among subjects with epistaxis treated with dabigatran. Results were compared with a group of epistaxis cases of individuals under anticoagulant therapy with VKA (acenocoumarol) and a control group without anticoagulation. ResultsSince its inclusion in our health system almost 3 years ago, 19 patients with epistaxis and concomitant use of dabigatran have been attended at the Emergency Unit in our hospital, as against 59 under VKA therapy and 144 without anticoagulation, with a mean admittance rate of 26%, 28% and 14%, respectively. In 3 out of 5 individuals admitted due to dabigatran treatment, previously unobserved renal failure was detected. Blood transfusion was needed in 80% of patients using dabigatran, 58% using VKA and 23% without anticoagulation. Invasive procedures to control nosebleed were required in 80%, 35% and 21%, respectively. Although haemorrhagic risk was lower in dabigatran cases, they showed the longest stay in the hospital when compared to the other groups. ConclusionsWith dabigatran, there are fewer cases of severe epistaxis than with acenocoumarol, but controlling them is more difficult.

Relation between frequency of activated partial prothrombin time measurements and clinical outcomes in patients after initiation of dabigatran: A two-center cooperative study

BackgroundAlthough activated partial prothrombin time (aPTT) has often been used as a biomarker for evaluating the safety of dabigatran use in patients with non-valvular atrial fibrillation (NVAF), the optimal frequency of aPTT measurements is unclear. This study aimed to identify the frequency distribution of aPTT measurements in clinical practice and its clinical significance. MethodsThis was a retrospective cooperative study conducted in 2 sites. All NVAF patients who underwent aPTT measurements before and after dabigatran treatment were included (n=380). The patients were divided into 2 groups according to the frequency of aPTT measurements during the first 3 months after drug prescription: Group A: infrequent group with only 1 measurement; and Group B: frequent group with ≥2 measurements. The clinical characteristics and outcomes were compared between the groups. ResultsThe frequency of aPTT measurements in the 3 months after dabigatran initiation varied: 240 patients underwent 1 measurement (Group A), and the remaining 140 patients underwent repeated measurements (Group B). There were significant differences in age and creatinine clearance (Ccr) between the groups (Group A vs. Group B: age 64.0±11.7 vs. 67.0±11.1 years, p=0.01; Ccr 83.8±30.3 vs.76.7±31.1mL/min, p=0.03). During the mean follow-up period of 310 days, there were no significant differences in the discontinuation rate and incidence of bleeding (17% vs. 15% and 5% vs. 3%, respectively; both not significant). In Group B, the aPTT rarely increased beyond twice the upper normal limit within the 3 months (2.1%), although the correlation between the initial and subsequent aPTT measurements was low (r=0.366). ConclusionsIn this retrospective study, the frequency of aPTT measurements after dabigatran initiation might have been dependent on patient characteristics. However, frequent aPTT measurements did not lead to a reduction in adverse clinical events.

Cost-effectiveness of dabigatran versus vitamin K antagonists for the prevention of stroke in patients with atrial fibrillation: A French payer perspective

Atrial fibrillation is the main cause of stroke, but the risk can be reduced, usually with vitamin K antagonists (VKAs) such as warfarin. The RE-LY atrial fibrillation study demonstrated that the rates of stroke and systemic embolism with dabigatran (an oral direct thrombin inhibitor) were similar to or lower than those with warfarin. To estimate the cost-effectiveness, from a French payer perspective, of dabigatran (150 or 110mg bid for patients<or≥80 years, respectively) versus warfarin. Cost-effectiveness was modeled using a Markov model in a cohort of 10,000 patients with atrial fibrillation followed over their lifetime. Events accounted for included ischemic stroke, systemic embolism, transient ischemic attack, hemorrhage, myocardial infarction and death. The model patient population matched the RE-LY patients. Dabigatran was compared with "trial-like" warfarin and "real-world" prescribing. Risks of clinical events were obtained from RE-LY. Event and follow-up costs were based on the French national tariff or published literature. Clinical events, QALYs, total costs and incremental cost-effectiveness ratios (ICERs) were calculated. The ICERs of dabigatran compared with "trial-like" warfarin and "real-world" prescribing were €15,838/QALY and €7473/QALY, respectively. Deterministic and probabilistic sensitivity analyses showed these to be robust to uncertainty and variability in the model parameters. The ICER for dabigatran was below €24,000/QALY or €36,000/QALY in 71% or 92%, respectively, of the simulations when compared with "trial-like" warfarin and 100% and 100%, respectively, when compared with "real-world" prescribing. This study suggests that the use of dabigatran in French atrial fibrillation patients is cost-effective, according to usually accepted thresholds.

Perioperative management of patients on new oral anticoagulants.

New oral anticoagulants (NOACs) offer an alternative to warfarin for preventing stroke in patients with atrial fibrillation. NOACs are expected to replace warfarin and other vitamin K antagonists for most of their indications in the future. Knowledge of the use of NOACs in the perioperative period is important for optimal care. Studies that reported on the use of NOACs were identified, focusing on evidence-based guidance relating to the perioperative period. PubMed was searched for relevant articles published between January 2000 and January 2014. The anticipated expanded clinical use of NOACs such as rivaroxaban (Xarelto™), apixaban (Eliquis™) and dabigatran (Pradaxa™) has the potential to simplify perioperative anticoagulant management because of fewer drug-drug interactions, rapid onset of action, predictable pharmacokinetics and relatively short half-lives. However, coagulation status cannot be monitored by international normalized ratio and no antidotes are currently available. In elective surgery, it is important to discontinue the use of NOACs, with special consideration of renal function as route of elimination. Guidelines for the management of bleeding complications in patients on NOACs are provided, and may be considered for trauma and emergency surgery. Haemodialysis could be considered for bleeding with use of dabigatran. Better options for reversal of the effects of NOACs when bleeding occurs may follow with novel drugs. Management of NOACs in elective and emergency conditions requires knowledge of time of last intake of drug, current renal function and the planned procedure in order to assess the overall risk of bleeding. Currently no antidote exists to reverse the effects of these drugs.

Benefit–Risk Assessment of Dabigatran in the Treatment of Stroke Prevention in Non-Valvular Atrial Fibrillation

Non-valvular atrial fibrillation (NVAF) is the most common clinically significant cardiac arrhythmia and is a common cause of stroke. The direct thrombin inhibitor dabigatran etexilate is approved for a variety of indications requiring anticoagulation, including stroke prevention in NVAF. Dabigatran does not require routine monitoring and exhibits only a few drug-drug interactions; however, impaired renal function needs observation. The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study comprised about 18,000 patients with NVAF who received dabigatran 110mg twice daily or 150mg twice daily, or dose adjusted warfarin. Compared with warfarin, dabigatran 110mg twice daily was associated with similar rates of stroke and systemic embolism, and lower rates of haemorrhage. Dabigatran 150mg twice daily was associated with lower rates of stroke and systemic embolism but similar rates of haemorrhage. The rate of intracerebral haemorrhage (ICH) was significantly lower in both dabigatran arms. Basing on the results of the RE-LY study, the net clinical benefit balancing stroke against ICH has been estimated with various settings (study data, registry patients). In patients with low stroke risk but at high risk of bleeding, only dabigatran 110mg twice daily had a positive net clinical benefit when compared with warfarin. In patients with higher stroke risks, both doses of dabigatran (110 and 150mg twice daily) had a positive net clinical benefit even if the bleeding risk was high. Registry data after approval of dabigatran indicate similar stroke/systemic embolism and major bleeding rates with dabigatran (both doses) compared with warfarin. Pharmacovigilance sources prove the anticipated bleeding risk, but a refined analysis of such data showed that bleeding rates associated with dabigatran use did not appear to be higher than those associated with warfarin. Dabigatran confers an advantage over warfarin regarding stoke prevention without the burden of the surveillance of vitamin K antagonists, especially in patients with high stroke risk. However, in elderly patients with impaired renal function or considerable bleeding risks, label advice regarding dosing needs strict observation.

SAFETY AND EFFICACY OF RIVAROXABAN AND DABIGATRAN IN OCTA- AND NONAGENERIANS WITH ATRIAL FIBRILLATION: A COMMUNITY-BASED EXPERIENCE

Despite the increasing use of dabigatran and rivaroxaban in the older-elderly as an alternative to warfarin to reduce the risk of stroke associated with atrial fibrillation, limited information is available on the efficacy and safety of these newer anticoagulants in this population. We

Use of continuous veno-venous haemodiafiltration therapy in dabigatran overdose

Context. Dabigatran etexilate is one of the newer oral anticoagulants and a direct thrombin inhibitor. Concerns regarding dabigatran's use include its lack of validated laboratory markers for measuring its anticoagulation effect, the impact of renal impairment on its clearance, and the lack of effective strategies for reversal of anticoagulation. Hemodialysis has been utilized to reverse the anticoagulant effects of dabigatran in therapeutic doses. However, hemodialysis may not be feasible in hemodynamically unstable patients. There is little data on clearance rates of dabigatran by continuous renal replacement therapies. Case details. A 66-year-old male presented following a poly-pharmacy overdose of 9 g of dabigatran in combination with metoprolol, amlodipine, olmesartan, and moxonidine. Eleven hours post overdose extracorporeal elimination was implemented as the patient developed worsening coagulopathy with an elevated international normalized ratio of 11 IU, an activated partial thromboplastin time of 115 s, and had renal impairment with a creatinine of 158 μmol/L. As the patient was hemodynamically unstable, continuous veno-venous hemodiafiltration was preferred over intermittent hemodialysis. Renal replacement therapy was performed for 32 h in total and the patient made a full recovery with no hemorrhagic complications or end organ injury. This patient developed a peak serum dabigatran level of 1560 ng/ml, 11 h postoverdose. Clearance of dabigatran via continuous veno-venous hemodiafiltration was calculated, using both the recovery and A-V pair methods, with a mean clearance of 58.1 and 31.9 ml/h, respectively, and a calculated mean extraction ratio of 0.2. Conclusion. There are few case reports and little experience when dabigatran is taken in overdose. This is a case report of a large dabigatran overdose presenting data on the extraction ratio and clearance of dabigatran using continuous veno-venous hemodiafiltration.

Evaluation of Dabigatran Bleeding Adverse Reaction Reports in the FDA Adverse Event Reporting System during the First Year of Approval

Evaluate dabigatran adverse event reports with a reported bleeding event and/or reported fatal outcome compared with warfarin. Retrospective analysis of the FDA Adverse Event Reporting System (FAERS) database. We identified reports from October 1, 2010, through December 31, 2011, in the United States listing dabigatran or warfarin as the primary suspected agent. Bleeding events and related outcomes were determined. A bleeding-related mortality rate was calculated based on national dabigatran treatment data. Dabigatran was the primary suspected agent in 9029 adverse reports. Of these, 2347 (26%) were bleeding events; a fatal outcome was reported in 348 (15%) of the bleeding events. In comparison, warfarin was the suspected agent in 2038 reports, of which 647 (32%) were reported as bleeding events. Among the warfarin bleeding reports, 46 (7.1%) reported a fatal outcome. Based on national dabigatran use and adverse bleed reports with fatal outcomes, we estimate a lower bound of 150 bleeding-related fatalities per 100,000 dabigatran patient-years. Because of underreporting bias, these estimates represent a lower bound on the population bleeding mortality rates. Reports from FAERS are subject to significant bias but suggest that fatal outcomes among dabigatran reports are higher in clinical practice than they were in controlled clinical trials.

Safety of new oral anticoagulants for patients undergoing atrial fibrillation ablation

The new oral anticoagulants (NOAC), dabigatran and rivaroxaban, have been demonstrated to be at least equivalent to warfarin for preventing cardiac thromboembolism (TE) in patients with atrial fibrillation (AF). However, there is limited data regarding use around catheter ablation (CA) procedures. We evaluated the risk of bleeding and TE complications associated with NOAC use during AF ablation. Consecutive patients undergoing AF ablation between January 2011 and 6 September 2013 were grouped based on peri-procedural anticoagulation regimen: (1) uninterrupted warfarin with therapeutic INR (WARF), n = 114, (2) dabigatran, n = 89, or (3) rivaroxaban, n = 98. NOACs were held for 24 h (dabigatran) or 36 h (rivaroxaban) prior to the procedure. Heparin infusion was initiated 6 h post-procedure for the NOAC groups; NOACs were resumed the morning after the procedure. Antral PVI was performed with activated clotting time (ACT) maintained >300 s. TE or bleeding complications during ablation and through 30 days were compared. Three hundred and one patients underwent ablation for paroxysmal (71%) or persistent (29%) AF. International Normalization Ratio (INR) for the WARF group was 2.0 ± 0.5. Baseline characteristics were similar among the groups. There were two TE events (asymptomatic cerebral emboli and TIA), and there were 17 bleeding events (large hematoma n = 4; pericardial effusion n = 6; persistent hematuria n = 1; pseudoaneurism/AV fistula n = 6). Of the six pericardial effusions, three required drainage. There was no significant difference in combined TE/bleeding risk among the groups (WARF vs. dabigatran vs. rivaroxaban; 6.2% vs. 6.7% vs. 6.0%; p = 0.82) CONCLUSIONS: In this group of AF patients undergoing CA, use of peri-procedure dabigatran or rivaroxaban compared to uninterrupted warfarin did not lead to an increase in bleeding or TE complications.