Management Of Oral Anticoagulants Research Articles

Clinical review: Clinical management of new oral anticoagulants: a structured review with emphasis on the reversal of bleeding complications.

New oral anticoagulants, including dabigatran, rivaroxaban, and apixaban, have been recently approved for primary and secondary prophylaxis of thromboembolic conditions. However, there is no clear strategy for managing and reversing their anticoagulant effects. We aimed to summarize the available evidence for clinical management and reversal of bleeding associated with new oral anticoagulants. Using a systematic review approach, we aimed to identify studies describing reversal strategies for dabigatran, rivaroxaban, and apixaban. The search was conducted using Medline, EMBASE, HealthSTAR, and grey literature. We included laboratory and human studies. We included 23 studies reported in 37 out of 106 potentially relevant references. Four studies were conducted in humans and the rest were in vitro and in vivo studies. The majority of the studies evaluated the use of prothrombinase complex concentrate (PCC), either activated or inactivated, and recombinant activated factor VII (rFVIIa). Other interventions were also identified. Laboratory studies suggest that hemostatic parameters and bleeding might be partially or completely corrected by PCC for rivaroxaban better than dabigatran. Studies in humans suggest that PCC might reverse the effects of rivaroxaban better than dabigatran assessed by hemostatic tests. We were not able to locate studies evaluating the clinical efficacy of these agents. The best available evidence suggests that PCC (activated or inactivated) might be the best option for reversing new anticoagulants. Evidence for rFVIIa is less compelling. There might be differences in the efficacy of reversing agents for different anticoagulants. Studies assessing the clinical efficacy of these reversal agents are urgently needed.

The perioperative management of new direct oral anticoagulants: a question without answers

New direct oral anticoagulant agents (DOAC) are currently licensed for thromboprophylaxis after hip and knee arthroplasty and for long-term prevention of thromboembolic events in non-valvular atrial fibrillation as well as treatment and secondary prophylaxis of venous thromboembolism. Some other medical indications are emerging. Thus, anaesthesiologists are increasingly likely to encounter patients on these drugs who need elective or emergency surgery. Due to the lack of experience and data, the management of DOAC in the perioperative period is controversial. In this article, we review available information and recommendations regarding the periprocedural management of the currently most clinically developed DOAC, apixaban, dabigatran, and rivaroxaban. We discuss two trends of managing patients on DOAC for elective surgery. The first is stopping the DOAC 1-5 days before surgery (depending on the drug, patient and bleeding risk) without bridging. The second is stopping the DOAC 5 days preoperatively and bridging with low-molecular-weight heparin. The management of patients on DOAC needing emergency surgery is also reviewed. As no data exist for the use of haemostatic products for the reversal of the anticoagulant effect in these cases, rescue treatment recommendations are proposed.

Anticoagulation Management in the Perioperative Phase of Implantable Cardioverter Defibrillator Implantation

According to the current guidelines, substitution of warfarin with heparin is recommended as perioperative management in patients with high risk of thromboembolism. Optimal management of oral anticoagulation in patients undergoing implantable cardioverter defibrillator (ICD) implantation, however, remains controversial. Bleeding complications among 273 consecutive patients undergoing initial ICD implantation were retrospectively analyzed. Patients were grouped according to medication at the time of device implantation: neither antiplatelet nor anticoagulation (N group, n=121); antiplatelet only (AP group, n=59); warfarin (W group, n=59); and heparin bridging (H group, n=34). The rate of the major bleeding complications, defined as hematoma requiring reoperation, cardiac tamponade, and pericardial effusion requiring additional hospital stay, was 1.7% in the N group, 0% in the AP group, 5.1% in the W group, and 17.6% in the H group (P<0.001, N group vs. H group). After multivariate adjustment, heparin bridging was a significant predictor of major bleeding complications (odds ratio, 7.44; 95% confidence interval: 2.06-26.89; P=0.0022). The international normalized ratio of 3 patients in the W group with major bleeding complications was 1.98 ± 0.10, and was significantly higher than in patients without them (1.31 ± 0.05, n=26, P<0.001). Heparin bridging increased the risk of bleeding complications at the time of ICD implantation.

WARFARIN MANAGEMENT IN HAEMODIALYSIS—ARE WE MEETING BRITISH HAEMATOLOGY SOCIETY STANDARDS?

We evaluated current oral anticoagulant management at our main dialysis unit and three satellite units against British Haematology Society (BHS) standards. These standards include patients meeting their target INR +/- 0.5 INR units for 60% of the time with an appropriate frequency of monitoring. Data were collected on anticoagulant prescribing and monitoring over one month. None of the four haemodialysis centres were able to achieve BHS standards for all patients. There was wide variability in monitoring frequency, some patients had 13 INRs and up to 10 dose changes. Satellite C had the most patients (63%) meeting BHS target. Satellite A and B both had 50% of patients meeting target. However, Satellite A, where all patients were dosed by anticoagulant clinic, had the least frequent blood sampling and no patients exceeded the therapeutic INR. Units that employed dosing by anticoagulant clinics demonstrated best outcome for INR target with the least frequency of sampling. Service design set up and monitoring pathways play a crucial role in achieving warfarin therapeutic targets in haemodialysis units.

Management of patients who are receiving warfarin or a new oral anticoagulant and require urgent or emergency surgery

An increasing number of patients are receiving long‑term oral anticoagulant therapy and the availability of new oral anticoagulants (OACs), which are easier to use than warfarin, will further expand the population of anticoagulated patients. As a consequence, an increasing number of patients will need perioperative anticoagulant management because of elective or nonelective surgery or procedures. The perioperative management of such patients is pertinent to a broad spectrum of physicians, including anesthesiologists, internists, and surgeons. The objectives of this review are to provide a clinically‑focused background on the pharmacology of warfarin and the new OACs and to suggest perioperative anticoagulant management strategies. This review will focus on the perioperative management of warfarin and new OACs who require urgent or emergent surgery or who require rapid anticoagulant reversal because of ongoing bleeding or high bleeding risk.

Novel Oral Anticoagulation in Management of Venous Thromboembolism, Atrial Fibrillation, and Acute Coronary Syndrome

Venous thromboembolism (VTE) is a major public health concern since the incidence of VTE rises substantially with age. Furthermore, the diagnosis can be elusive since patients can present differently, causing delay in diagnosis and initiation of treatment and resulting in major morbidity and mortality. In addition to accuracy and precision in diagnosis, antithrombotic therapies are the cornerstones of VTE management. In traditional paradigm, vitamin K antagonists (warfarin), indirect factor Xa inhibitors, and heparin are the foundation in management of VTE. Warfarin has been the only available oral anticoagulant therapy for several decades. Although warfarin is effective in both treatment and prophylaxis against VTE, there are several limitations. Therefore, the novel anticoagulation therapies, including rivaroxaban, apixaban, and dabigatran etexilate, have apparent advantages over warfarin in terms of clinical efficacy and adverse effects. The objective of this review is to describe the background and clinical implications of these novel anticoagulants.

Home-monitoring of oral anticoagulation vs. dabigatran

Oral anticoagulation with vitamin k antagonists (VKAs) requires regular testing and dose adjustment. Home-monitoring (self-testing or self-management) is more effective than usual management. Dabigatran, does not require dose-adjustment and appears to be more effective at reducing the risk of stroke with similar risks of bleeding in patients with atrial fibrillation (AF). Dabigatran, however, has not been compared to the home-monitoring. It was the objective to evaluate the efficacy of dabigatran compared with home-monitoring of oral anticoagulation with VKAs. Randomised controlled trials (RCTs) comparing usual management of oral anticoagulation with home-monitoring, dabigatran with usual management, and RCTs comparing dabigatran with home-monitoring and including patient-important outcomes (thromboembolic events, death and major bleeding) were eligible. For our direct comparison we calculated pooled relative risks (RRs) using the Mantzel-Haenzel random effect model. For the indirect comparison we estimated lnRRs and back transformed to RR. We evaluated the quality of the evidence with the GRADE system. Dabigatran, compared with warfarin, was associated with lower rates of stroke or thromboembolism and systemic embolism but similar rates of major haemorrhage and death. Dabigatran 150 mg also increased non-significantly the rate of myocardial infarction. The quality of the evidence was high. Our indirect comparison of home-monitoring of oral anticoagulation versus dabigatran showed no convincing differences in the risk of thromboembolism, death or major bleeding. The estimates for self-management vs. dabigatran showed stronger but still non-significant trends. The quality of the evidence was low. In conclusion, the indirect comparison of home monitoring of oral anticoagulation with dabigatran suggests that the treatments have similar impact on thrombosis, bleeding and death. However, the confidence in the estimate of effect is low to very low. Our analyses contrast with the available comparison of dabigatran with conventional warfarin monitoring.

Long-term self-management of anticoagulation therapy after mechanical heart valve replacement in outside trial conditions

In this investigation, we hypothesize that quality of oral anticoagulation (OA) and long-term outcome after mechanical heart valve (MHV) replacement with self-management (Self-M) of OA is superior to conventional anticoagulation treatment (Conv-T), even in outside trial conditions. One hundred sixty patients (78.8% aortic valve replacements) were trained in international normalized ratio Self-M and 260 patients (86.2% aortic valve replacements) preferred Conv-T. Mean follow-up was 8.6±2.1 years, representing 3612 patient-years. During follow-up, 37.2% bleedings and 10.6% thromboembolic events were recorded in the Self-M group versus 39.6% bleedings (P=0.213) and 15.4% thromboembolic events (P=0.064) in the Conv-T group. Serious adverse events were significantly lower in the Self-M group [grade III bleeding events causing disability or death: 0 versus 4.6% (P=0.03); grade III thromboembolic events: 0.6 versus 5.0% (P=0.011)]. Patients with Self-M were significantly more satisfied with their OA management and their quality of life (P<0.001). Actuarial survival after 1, 5 and 10 years was 100, 99 and 97 with Self-M and 100, 95 and 81% with Conv-T, respectively (P<0.001). Univariate risk factors for mortality were age (P=0.008), type of operation (P=0.021) and conventional OA (P<0.001). In multivariate analysis, only conventional OA reached significance (P<0.001). We conclude that in a routine setting under outside trial conditions Self-M of OA improves long-term outcome and treatment quality.

Role of Pharmacogenomics in the Management of Traditional and Novel Oral Anticoagulants

Warfarin is the most commonly prescribed oral anticoagulant. However, it remains a difficult drug to manage mostly because of its narrow therapeutic index and wide interpatient variability in anticoagulant effects. Over the past decade, there has been substantial progress in our understanding of genetic contributions to variable warfarin response, particularly with regard to warfarin dose requirements. The genes encoding for cytochrome P450 (CYP) 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) are the major genetic determinants of warfarin pharmacokinetics and pharmacodynamics, respectively. Numerous studies have demonstrated significant contributions of these genes to warfarin dose requirements. The CYP2C9 gene has also been associated with bleeding risk with warfarin. The CYP4F2 gene influences vitamin K availability and makes minor contributions to warfarin dose requirements. Less is known about genes influencing warfarin response in African-American patients compared with other racial groups, but this is the focus of ongoing research. Several warfarin pharmacogenetic dosing algorithms and United States Food and Drug Administration-cleared genotyping tests are available for clinical use. Clinical trials are ongoing to determine the clinical utility and cost-effectiveness of genotypeguided warfarin dosing. Results from these trials will likely influence clinical uptake and third party payer reimbursement for genotype-guided warfarin therapy. There is still a lack of pharmacogenetic data for the newly approved oral anticoagulants, dabigatran and rivaroxaban, and with other oral anticoagulants in the research and development pipeline. These data, once known, could be of great importance as routine monitoring parameters for these agents are not available.

Long-Term Oral Anticoagulant Management Associated with Routine Medical Care (RMC) In Patients with Non-Valvular Atrial Fibrillation (NVAF) In Canada,

Abstract 4192 Introduction:There are no prospective, long-term studies describing the process and quality of care, resource utilization (RU), and quality of life (QoL) associated with being on oral anticoagulant therapy for non-valvular atrial fibrillation (NVAF) patients managed through routine medical care (RMC) in Canada. Methods:Resource utilization associated with Oral Anticoagulant Management (ROAM) is a prospective cohort study being conducted across 9 Canadian provinces whose objective is to describe the process and quality of care, RU, clinical events and health utility scores associated with long-term oral anticoagulant (warfarin) therapy in patients with new onset or chronic NVAF. Eligible, consenting patients are followed for 48 weeks and complete a weekly study diary providing data on international normalized ratio (INR) test dates and values, RU associated with warfarin monitoring, and all physician visits, procedures and hospitalizations. Health utility scores, representing the patient's health state, measured using the EuroQol-5D (EQ-5D) standardized QoL instrument are collected every 4 weeks. INR test values and dates and source documentation around patient reported clinical events are also collected from the participating physicians. Results:497 out of a planned enrolment of 600 patients have been recruited. 180 patients with completed 48 week follow-up and physician-provided INR values are included in this analysis, 98% from primary care physicians and specialists (RMC) and 2% from anticoagulant clinics. Median age [range] was 75 [39, 90] years with 67% males. Common co-morbidities were hypertension (60%) and ischemic heart disease (27%). Estimated median [range] time since NVAF diagnosis was 4 [0, 32] years. Physicians reported a total of 2484 INR tests over the study duration (a mean of 13.8 tests per patient) while patients recorded 2711 tests being completed in their diaries over the same time period (a mean of 15.06 tests per patient). Of the 2711 patient reported tests only 1914 INR results (71%) were communicated back to patients via telephone (70%) or in person (15%). Median [quartile] time between the INR test and the patient acquiring the results was 1.4 [1.0, 2.5] days. The INR test dates provided by physicians matched the dates recorded by patients in the diary 67% of the time. 51 (28%) of patients recorded no INR values. Of the 129 patients with at least one recorded INR value, physician and patient INR values matched completely for only 8 (4%) patients and matched on average 62% of the time (range 30% to 98%) for the rest. Mean [95% CI] time in therapeutic range (TTR) by the Rosendaal method was 67% [64%, 71%] using physician reported values and 67% [62%, 72%] based on patient reported values. Mean INR testing frequency was 30 days following an INR in the therapeutic range, 25 days following an INR of less than 2 and 22 days following an INR greater than 3. Three strokes and 3 bleeds were self-reported in 5 patients (9%) that are being adjudicated. The initial mean [95% CI] health utility score was 0.85 [0.83, 0.88]. A decrease in health utility score was observed in 133 (74%) of the patients based on a random effects regression model. Fixed effect estimate of the mean [95% CI] change in health utility scores per 6 months was −0.01 [0, −0.02]. Covariates (age, gender and time since diagnosis) were investigated but had limited effect on the health utility score. Conclusions:This is the first prospective cohort study of NVAF patients on long-term warfarin therapy being monitored primarily through RMC in Canada. The majority of patients are monitored via telephone with frequent miscommunication between health care providers and patients about INR results and delays in getting results to patients. TTR is higher than previously reported for RMC, which may suggest a self-selection bias for better quality physician-patient combinations. Although frequency of testing was appropriate for in-range INRs, the times to testing after out-of-range results appear delayed. Analysis of health utility scores showed a small decrease in health status over time in this cohort of patients with generally high health utility scores. Relationship between TTR and clinical events will be presented. Disclosures:Selby:Boehringer Ingelheim: Honoraria, Research Funding. Mittmann:Boehringer Ingelheim: Research Funding. Isogai:Boehringer Ingelheim: Research Funding. Kaus:Boehringer Ingelheim: Research Funding. Koo:Boehringer Ingelheim: Research Funding. Sealey:Boehringer Ingelheim: Research Funding.

Abstract P97: Operational Redesign of an Outpatient Anticoagulation Management Program- The Vanderbilt Experience

The 2008 Joint Commission National Patient Safety Goals required healthcare organizations to adopt practices to reduce the likelihood of harm associated with use of anticoagulation therapy. Assessment of our anticoagulation programs in 2008 demonstrated gaps that did not meet these new requirements. Patients were enrolled in two large anticoagulation clinics (separately managed by pharmacy and cardiology) with smaller programs linked to their clinical service lines. Identified gaps included: separate programs that were not standardized and had no integrated governance/oversight, inadequate budget and staffing models to meet growing demand, lack of unified practice policy and anticoagulation information systems, and lack of standardized quality measures and reporting. Vanderbilt leadership commissioned an Anticoagulation Executive Steering Committee to perform an operational redesign of the anticoagulation programs to meet National Patient Safety Goals. The committee appointed working groups to: evaluate and redesign clinical operations and finance, perform a technology assessment to develop standard anticoagulation information systems, and develop standardized reporting of quality metrics. The key redesign features were: 1) merging of the existing anticoagulation clinics into a single unified program; 2) dedicated institutional budget for ambulatory anticoagulation services with costs shared across the clinical enterprise; 3) implementation of standard policies and protocols for anticoagulation management and education; 4) creation of dedicated oral anticoagulation management software (AMS) fully integrated into the electronic health record; 5) creation of medical director and program manager positions for operational oversight of the unified program, and an Anticoagulation Oversight Committee for clinical practice supervision; 6) development of a bundle of quality metrics and operational/clinical data reports derived from the AMS. Our redesign experience provides a blueprint for other organizations that provide anticoagulation management to meet National Patient Safety Goals.

Abstract P260: Superior Oral Anticoagulation Management With Self Testing and Automated Online Management; An Interim Analysis

Background: The safety and efficacy of warfarin therapy is critically dependent on control of the international normalized ratio (INR). One-third of 3,587 warfarin-treated patients with their INR time in the therapeutic range (TTR)&gt; 75% had a 50% lower major event rate compared to the one-third whose TTR was &lt; 60%. Objective: Assess the impact of three interventions on INR control and management time. Interventions included weekly INR self testing, daily low dose vitamin K, and online management. Methods: Sixty-three patients who were at least 18 years of age, had completed at least 7 months of warfarin therapy, and did not have a diagnosis of antiphospholipid antibody or HIV/AIDS provided written informed consent. INR control was assessed for 6 months pre-study and for up to 12 months during the study. INR control was reported as %TTR, %TTR +/- 0.3 INR units, and % time at an INR below 1.5 or above 5. Clinician time required for each “virtual visit” was recorded and 1 minute was assigned for each automated visit. Results: Eight of 63 patients were excluded (4 withdrew consent the first week, 3 were early protocol violaters, and 1 had warfarin discontinued at study day 11). Fifty-five patients provided 26.83 patient-years of pre-study data during which the TTR was 56.83%, TTR +/-0.3 INR units was 82.55%, and time below 1.5 or above 5 was 2.41% and 0.09%, respectively. Of 54.14 patient-years of study data, TTR improved to 79.65% TTR, 93.57% for TTR +/-0.3 INR units, and 0.4% and 0.07% for time below an INR of 1.5 or above 5, respectively (see Table ). Clinician management required 8.94 minutes per 4 “virtual visits” per patient per month. Summary: Weekly INR self testing, daily low dose vitamin K, and online automated management improved the TTR by 22%; a degree of improvement that has been associated with a 50% reduction in stroke, heart attack, major bleeding, and death. INRs were rarely very far out of range and management required clinician time of less than 10 minutes per patient per month. INR Control Pre-Study vs Study Period End Point Pre-Study n=55, 26.83 patient-years Study, n=55, 54.14 patient-years % Time in Range 56.83 79.65 % Time in Range +/- 0.3 INR units 82.55 93.57 % Time INR &lt; 1.5 2.41 0.40 % Time INR &gt; 5 0.09 0.07 # (%) Patient with TTR &gt; 75% 11 (20) 39 (70.1) # (%) Patients with TTR +/- 0.3 INR &gt; 75% 17 (30.1) 55 (100) # (%) Patients with TTR &lt; 60 30 (54.5) 4 (7.3) # (%) Patients with TTR +/- 0.3 INR &lt; 60% 7 (12.7) 0 (0.0)

Evaluation of a new standardized protocol for the perioperative management of chronically anticoagulated patients receiving implantable cardiac arrhythmia devices

Perioperative management of oral anticoagulation (OAC) in patients receiving pacemakers or implantable cardioverter-defibrillators remains an issue of concern. We sought to evaluate the safety and the effect on the hospital length of stay of a new standardized protocol for perioperative management of OAC in this setting. The new standardized protocol classified patients according to a renewed evaluation of their thromboembolic (TE) risk. Briefly, patients were considered at moderate-to-high TE risk if they had a mechanical valvular prostheses irrespective of type and location or atrial fibrillation associated with a CHADS(2)score of ≥2, mitral stenosis or previous stroke, and underwent device implantation without stopping OAC (OAC continued, n = 129). Complete interruption of OAC before surgery was performed in low-TE-risk patients (OAC interrupted, n = 82). A retrospective cohort of patients managed with a classic heparin-bridging strategy served as a control group, with 62 patients considered at moderate-to-high TE risk according to previous guidelines (receiving pre- and postoperative low-molecular-weight heparin) and 146 considered at low TE risk (receiving only low doses of postoperative low-molecular-weight heparin). TE events were comparable between the 2 strategies. Patients entering the new standardized protocol had significantly lower rates of pocket hematoma (2.3% for OAC continued vs 17.7% for moderate-to-high TE risk bridging controls, P = .0001, and 0% for OAC interrupted vs 13% for low-TE-risk bridging controls, P <.0001) and shorter hospital stays. A mean of 3.34 hospitalization days per patient were saved with the new standardized protocol, with an estimated cost savings of €850.83 per patient. Implantation of the new standardized protocol resulted in a significant reduction in bleeding complications and hospital stays, with adequate protection against TE events and significant cost savings.

Segurança da ablação de fibrilação atrial com RNI terapêutico: comparação com a transição com heparina de baixo peso

The ideal management of oral anticoagulation (OAC) before and after catheter ablation for atrial fibrillation (AF) is still controversial. To compare two anticoagulation strategies for catheter ablation for AF: warfarin withholding and use of low-molecular-weight heparin (LMWH); and maintenance of warfarin and therapeutic INR (between 2.0 and 3.0). 140 patients (pt) with persistent/permanent AF undergoing catheter ablation for AF were divided into two groups: Group I (70 pt), in which warfarin was withheld five days prior to the procedure and transition to LMWH was used (enoxaparin: 1 mg/kg 2x/day before ablation, and 0.5 mg/kg 2x/day after ablation); Group II (70 pt), in which warfarin was not withheld and the procedure was performed with therapeutic INR. Both groups received intravenous heparin (ACT > 350 seconds) during ablation. In Group I, one pt (1.4%) had a major hemorrhagic complication and four pts (5.7%) had minor hemorrhagic complications. In Group II, two pts (2.8%) had minor hemorrhagic complications and one pt had a major bleeding, which occurred after using LMWH due to INR < 2.0. None of the groups had thromboembolic complications or cardiovascular death over a period of 16 ± 8 months. Catheter ablation for AF without withholding OAC and with therapeutic INR is a strategy that has similar safety and efficacy when compared with the traditional transition to LMWH, avoiding the potentially inadequate anticoagulation of the initial post-ablation period.

Management of patients receiving oral anticoagulants using computer dosing software – does everyone agree? Data from a UK NEQAS (blood coagulation) exercise

The quality of anticoagulation management is not readily or frequently assessed, particularly between different centres. This study sought to evaluate agreement in oral anticoagulant management decisions between participating centres in UK NEQAS programmes. Participants were asked to indicate whether they used computerized dosing support software (CDSS) and to complete a series of questions with respect to anticoagulant management provision. Four clinical scenarios were provided, together with past and current International Normalised Ratio (INR) results. Participants were asked to provide recommendations on the target INR they would assign to the patient, the dose of warfarin and a recall interval. Seven hundred and fifty-nine centres returned results, of which 28% were enrolled in the hospital-based EQA programme, and 72% were participants in the point-of-care testing programme. Six hundred (79%) reported use of CDSS. In one straightforward scenario, there was 99% agreement in dose recommendation. However, for three more complex scenarios, differences were apparent in target INRs employed and both dose and recall recommendations. In some cases, differences related to the software system employed. The study emphasizes large variation in the approach to managing these scenarios and warrants further investigation, together with education including promoting national guidelines for the assignment of target ranges.

Knowledge and Wishes of Patients as Regards Vitamin K Antagonists: a Cross-sectional Survey inWestern Brittany, France

ObjectiveWe aimed to investigate patients’ educational wishes and patients’ perception of their knowledge of anticoagulants. Material and methodsOne thousand patients were randomly sampled from a list of patients living within the Brest district (France) affiliated to the National Health Insurance System and who had been reimbursed after the delivery of vitamin K antagonists in May 2007. A 56-item questionnaire has been mailed along with an information letter and a reply-paid envelope enclosed. ResultsSome 647 questionnaires were received; 82% of responders declared having been informed. Information was globally perceived as complete although alleged as being insufficient as regards bleeding management. Management of oral anticoagulants appears correct; however, only 28% of responders stated having a surveillance booklet; 63% of responders would like information and elicited oral information from their general practitioner. ConclusionOur study highlighted the importance of general practitioners in the French health system when thinking about implementing an educational program on anticoagulation.

Safety and efficacy of warfarin in paediatric patients with prosthetic cardiac valves: a retrospective audit

IntroductionGuidelines for warfarin management in children are essentially extrapolated from adult evidence. This study aimed to address that lack of paediatric-specific data regarding warfarin safety and efficacy for this population. Materials and MethodsA retrospective clinical audit was conducted within a cardiac referral centre incorporating a paediatric anticoagulation service. Children (0–16years) with a prosthetic cardiac valve were included. Warfarin related outcomes were collected between January 1st 2004 and December 31st 2009. Analysis included the percentage of INR tests within, above, or below the target therapeutic range (TTR). Adverse event data was collected regarding major bleeding and thrombotic events. Results75 patient years of warfarin therapy were recorded. 44.0% of INR tests were within the TTR. INR tests not within the TTR were twice as likely to be sub-therapeutic. Children with aortic prosthetic valves achieved their TTR less frequently than children with prosthetic mitral or tricuspid valves. There were no thrombotic events and 3 major bleeding events. ConclusionsAlthough less than 50% of INR results were within the TTR, oral anticoagulant management resulted in acceptable safety and efficacy outcomes for this cohort. Further studies are needed to confirm optimal paediatric-specific warfarin management strategies for children with prosthetic heart valves.

Quality of management of oral anticoagulation as assessed by time in therapeutic INR range in elderly and younger patients with low mean years of formal education: a prospective cohort study

despite the overwhelming evidence of its effectiveness, oral anticoagulation continues to be underused in the elderly, presumably due to physicians' misconceptions when estimating bleeding risk and ability to comply with treatment. to investigate the quality of anticoagulation control among deprived elderly and younger patients. prospective observational study. a public anticoagulation clinic in a developing country. all adult patients on intended long-term (>90 days) oral anticoagulation. We studied 171 patients (79 elderly and 92 non-elderly) with a mean follow-up of 273 ± 84.9 days. the main outcome measure was the quality of anticoagulation management as measured by the time in therapeutic (TTR) international normalised ratio (INR) range. Elderly patients (≥60 years) were compared with younger patients with respect to the educational level and co-morbidities. the mean number of years of formal education was 4.37 ± 3.2 years. The mean TTR was 62.50 ± 17.9% in non-elderly and 62.10 ± 16.6% in elderly (P = 0.862) subjects, despite the higher prevalence of co-morbidities in the latter group: heart failure (46.3 versus 28.6%, P = 0.042), diabetes mellitus (22.8 versus 8.7%, P = 0.011), renal failure (estimated glomerular filtration rate <50 ml/min: 38.0 versus 7.1%, P < 0.001) and polypharmacy (84.8 versus 58.7%, P < 0.001). Fifty elderly and 84 non-elderly subjects require little or no assistance in taking medications. Among them, the elderly had lower educational levels (3.42 ± 2.5 versus 5.55 ± 3.4 years of formal education, P < 0.001) and higher rates of cognitive impairment (34.0 versus 13.1%, P = 0.004), but a similar mean TTR (62.46 ± 16.1 versus 63.02 ± 17.8%, P = 0.856). The oldest (≥75 years) patients did as well as those aged ≤50 years (mean TTR: 62.54 ± 16.0 versus 62.23 ± 16.4%, respectively, P = 0.98). good-quality management of oral anticoagulation is achievable in deprived populations attending an anticoagulation clinic. Elderly patients may experience similar quality of anticoagulation despite having higher levels of co-morbidities and polypharmacy. These results add evidence to the safety of such therapeutic interventions in the elderly.

Home Management of Oral Anticoagulation via Telemedicine Versus Conventional Hospital-Based Treatment

We have developed an expert computer system for the control of oral anticoagulation therapy, accessible by the patients via their own computer. To investigate if the weekly measurement and dosing of international normalized ratio (INR) at home using the online Internet-based system was superior to conventional treatment, we performed a randomized, controlled trial. All 669 patients in our anticoagulation clinic were asked to participate in the trial, providing that they had Internet access and could use the CoaguChek XS system. A total of 140 patients were included and randomized to (A) once weekly measurement and report online, (B) twice weekly measurement and report online, and (C) continued conventional treatment with INR measurement in the lab every 4 weeks and dose adjustment by letter. Group A had 79.7% (95% CI 79.0-80.3) of time in therapeutic range (TTR), group B 80.2% (95% CI 79.4-80.9) of TTR, and group C 72.7% (95% CI 71.9-73.4) TTR. Groups A and B perform statistically significantly better than the conventional group C, with a difference of TTR of 7% points (p < 2.2 × 10(-16)), whereas no difference was seen between A and B. Home measurement of INR and the reporting and dosing of results online once a week increase TTR from 72% to 79% as compared to conventional computer-assisted monitoring in an anticoagulation clinic.

Continuation of warfarin during pacemaker or implantable cardioverter-defibrillator implantation: A randomized clinical trial

Management of oral anticoagulation in patients undergoing pacemaker (PPM) or implantable cardioverter-defibrillator (ICD) implantation remains controversial. Prior studies demonstrate that continuation of warfarin may be safer when compared with strategies requiring interruption and/or heparin bridging. Limited data from randomized trials exist. We conducted a randomized trial to determine whether warfarin continuation is superior to warfarin interruption during PPM or ICD implantation. Patients on oral anticoagulation referred for PPM or ICD implantation were randomized to warfarin continuation versus interruption. Patients randomized to warfarin interruption were further stratified into two groups based on their risk for thromboembolic events in the absence of warfarin. Moderate-risk patients were randomized to warfarin continuation versus warfarin interruption. High-risk patients were randomized to warfarin continuation versus warfarin interruption with heparin bridging. The primary combined outcome included thromboembolic events, anticoagulant-related complications, or any significant bleeding necessitating additional intervention or discontinuation of anticoagulation. We studied 100 patients (average age 70.8 years, 21% female, mean body mass index 28.4) who underwent 64 ICD and 36 PPM implantations. Fifty patients were assigned to continue warfarin. The randomized groups were well matched. Among patients randomized to warfarin interruption, there were two pocket hematomas, one pericardial effusion, one transient ischemic attack, and one patient who developed heparin-induced thrombocytopenia. No events were noted among patients continuing warfarin (P = .056). While the results were not statistically significant, there was a trend toward reduced complications in patients randomized to warfarin continuation. This strategy should be considered in patients undergoing PPM or ICD implantation.