Quality Of Oral Anticoagulation Research Articles

Quality of Oral Anticoagulation with Vitamin K Antagonists and Direct Oral Anticoagulants in ‘real-World’ Patients: Lessons from a Five Years Audit Study

Background: Even with the introduction of direct oral anticoagulants (DOACs), anticoagulation clinics (ACs) stand with a key role in monitoring. Indeed, routine evaluation by health care professionals is recommended as it is with vitamin K antagonists (VKA) with adjustments in practices of anticoagulation management services. Quality of oral anticoagulation (QOA) is associated to better clinical outcomes in those patients with indications for such therapy. It is well established that patients receiving VKA therapy, maintenance of an international normalized ratio (INR) in the therapeutic range is essential for treatment efficacy and safety. It has been reported that ACs should aim for a time in therapeutic range (TTR) between 70-80% to optimize benefit and minimize the risk of adverse events. So far, QOA for DOACs is not fully established. Aim: Since few clinical data are available considering the new era of ACs, this study aims to describe actual trends and QOA of an AC at a large academic medical hospital. Methodology: We retrospectively analyzed 23275 appointments of 5 consecutive years (May 2018 to May 2023), corresponding to 930 patients that are regularly followed up at an outpatient AC of a central hospital under anticoagulation for at least 8 weeks. TTR (≥70%) determined by Rosendaal method was used for patients under AVK and for those individuals in DOACs, QOA was considered the presence of therapeutic plasma levels of the drugs after the European Heart Rhythm Association 2021 in, at least, one determination. Patients were divided according to target INR in 3 groups: Group 1 with target INR 2-3, including 809 patients mean age 65±18 years (mean±SD), majority (36.6%) with atrial fibrillation (AF); Group 2 with target INR 2.5-3.5, including 92 patients with mean age 70±11 years, majority (85.9%) with mechanical heart valves; Group 3 with target INR 3-4, including 29 patients with mean age 63±15 years, majority (55.5%) with antiphospholipid syndrome. Seventy patients were under DOACs (apixaban in 74.3%), with mean age of 71±17 years, majority (62.9%) with non-valvular AF, were included in Group 1 and all individuals were under direct inhibitors of factor Xa. Descriptive statistics (mean, standard deviation, minimum, maximum, chi-square), inferential statistics (t-test, A-Nova and effect sizes) tests were performed. Results: The 930 patient population, 52.2% female, mean age of 65±18 years and 87% in Group 1, showed a mortality of 17%. The mean recall interval between appointments was superior to 90 days in 94% of the population. The individuals who died in comparison with the survivors showed higher frequency of AF (54.1%) [ χ 2= 47.099; p<.001; φ=.225], were from Group 1 (93%) [ χ 2= 6.641; p=.036; φ=.085], male (59.2%) [ χ 2= 10.103; p=.001; φ=-.104] and older [76±12 vs .63±18 years (p<.001), respectively]. No differences were noticed in mortality between AVK and DOACs [ χ 2= 1.828; p=.401; φ=-.044], even DOAC patients being older than AVK patients (71±17 vs 65±17; p=.005), respectively. QOA associated with mortality being the individuals who died with higher frequency of no QOA (21.9% vs 13.9%) [ χ 2= 8.126; p=.004; φ=-.101] respectively. The individuals on AVK from Group 1 corresponding to 86% of total population showed a mean TTR of 76%, patients from Group 2 had a TTR of 72% and patients in Group 3 had TTR of 55%. From the individuals under DOACs, only 30% had at least one determination of plasma levels of the drug and all but one showed therapeutic levels. Comparatively with our previous studies related to the periods of 2006-2012 and 2012-2018, we noticed a significant decrease in patient population / appointments size (2087/ 61988) (1587/ 37931),(p <.001) with an increase of TTR in Group 1 (1927/1430 patients) (83% /72%) and Group 2 (120/125 patients) (74% / 69%) but a TTR decrease in Group 3 (40 / 32 patients) (54% / 60%) (p <.001). respectively. Mortality in the 2012- 2018 period was 18%. Conclusions and Discussion: The trends of decreasing the number of anticoagulated patients at our AC with an overall good quality of monitoring but with a low percentage of individuals under DOACs suggests that the majority of anticoagulated population is on these drugs without routine follow up in opposition to the recent recommendations. Our study underlines the importance of the quality of anticoagulation monitoring on mortality that was no different from the previous years before SARS-CoV- 2 pandemic nor between AVK and DOACs.

Assessment of the relationship between the level of patient knowledge on warfarin therapy and the quality of oral anticoagulation: A systematic review and meta-analysis.

The present study aimed to investigate the relationship between the level of patient knowledge on warfarin therapy and the quality of oral anticoagulation. This is a systematic review and meta-analysis written on the basis of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Searches at MEDLINE, EMBASE, Scopus and LILACS electronic databases were carried out on February 13, 2023, using the descriptors "Patient Medication Knowledge", "Patient Education as Topic", "Health Education", "Patient Education" and Warfarin. The steps of selection, data extraction and quality analysis of articles were performed independently by two reviewers. The analysis was performed considering patient knowledge as a possible modifier of time in therapeutic range (TTR). The meta-analysis included studies that reported the correlation coefficient (Pearson or Spearman) between patient knowledge and TTR. A subgroup analysis was performed according to questionnaires employed to measure patient knowledge. Twelve studies were selected with an overall sample size of 7634 participants and mean age 58.2 (standard deviation (SD)±12,8) years. Eleven (92.0%) cross-sectional studies. The mean TTR was 57.8% (SD±11,3%) and the average level of knowledge was 60.4%. The meta-analysis indicated that patient level of knowledge on warfarin therapy was moderately associated with TTR (rs = 0.435; 95% confidence interval (CI) = 0.163-0.645; I2 = 96%). Subgroup analysis indicated association between knowledge level and TTR in studies employing the OAK test (rs = 0.617; 95% CI = 0.192-0.847; I2 = 97%) and the AKA (rs = 0.269; 95% CI = 0.002 to 0.501; I2 = 94%). However, the subgroup analysis presented no significant difference between them (p = 0.14). The meta-regression showed a non-significant negative effect of age on the correlation (estimate = -0.028, 95% CI = -0.073 to 0.016, p = 0.207). No publication bias was noted (p = 0.881). To our knowledge, this is the first systematic review and meta-analysis gathering evidence about the relationship between the level of patient knowledge on oral anticoagulation with warfarin and TTR. The implementation of structured and patient-centered educational interventions is essential to effectively increase the level of patient knowledge and, thus, to improve the quality and safety of warfarin therapy. Systematic review registration number: PROSPERO CRD42023398030.

The impact of mental health conditions on oral anticoagulation therapy and outcomes in patients with atrial fibrillation: A systematic review and meta-analysis

One third of patients with atrial fibrillation (AF) are estimated to suffer from mental health conditions (MHCs). We conducted a systematic review and meta-analysis to investigate the impact of MHCs on the prevalence and quality of oral anticoagulation (OAC) therapy and outcomes in patients with AF. Medline database was searched for studies published before March 1st 2021 evaluating AF patients with comorbid MHCs reporting on the prevalence of OAC therapy, time in therapeutic range (TTR) in warfarin-receiving patients, adherence to OAC therapy or adverse outcomes (ischemic stroke, hemorrhage or mortality). Studies reporting on outcome events were included in the meta-analysis. The literature search yielded 17 studies including 977,535 patients that fulfilled the inclusion criteria of this review. AF patients with MHCs had a lower prevalence of OAC use and poorer TTR compared with patients without MHCs. Evidence on OAC quality in patients receiving direct oral anticoagulants (DOACs) was minimal and inconclusive. A decrease in depression-associated deficit in OAC prevalence was observed after the introduction of DOACs. Pooled analysis of five studies reporting on outcomes showed that MHCs were an independent risk factor for both stroke (RR 1.25, 95%CI 1.08–1.45, I2 0%) and major bleeding (RR 1.17, 95%CI 1.08–1.27, I2 27%). Data on mortality were lacking and therefore not included in the meta-analysis. Evidence on the impact of specific MHCs on the outcomes were inadequate. In conclusion, MHCs are independent risk factors for stroke and major bleeding in patients with AF. Future studies are needed to confirm the findings of this meta-analysis, to evaluate the prognostic impact of different MHCs and to clarify whether the introduction of DOACs might have improved the outcomes of these patients.

Gut Microbiota and the Quality of Oral Anticoagulation in Vitamin K Antagonists Users: A Review of Potential Implications.

The efficacy and safety of vitamin K antagonists (VKAs) as oral anticoagulants (OACs) depend on the quality of anticoagulation control, as reflected by the mean time in therapeutic range (TTR). Several factors may be involved in poor TTR such as comorbidities, high inter-individual variability, interacting drugs, and non-adherence. Recent studies suggest that gut microbiota (GM) plays an important role in the pathogenesis of cardiovascular diseases, but the effect of the GM on anticoagulation control with VKAs is unknown. In the present review article, we propose different mechanisms by which the GM could have an impact on the quality of anticoagulation control in patients taking VKA therapy. We suggest that the potential effects of GM may be mediated first, by an indirect effect of metabolites produced by GM in the availability of VKAs drugs; second, by an effect of vitamin K-producing bacteria; and finally, by the structural modification of the molecules of VKAs. Future research will help confirm these hypotheses and may suggest profiles of bacterial signatures or microbial metabolites, to be used as biomarkers to predict the quality of anticoagulation. This could lead to the design of intervention strategies modulating gut microbiota, for example, by using probiotics.

Quality of Oral Anticoagulation with Vitamin K Antagonists in ‘Real-World’ Patients: Lessons from a Six Years Audit Study

Introduction: Among patients receiving vitamin K antagonists (VKA) therapy, maintenance of an international normalized ratio (INR) in the therapeutic range is essential for treatment efficacy and safety. This requires regular monitoring and appropriate dose adjustment. It has been reported that anticoagulation clinics should aim for a time in therapeutic range (TTR) between 70-80% to optimize benefit and minimize the risk of adverse events. Previously (in a study between September 2006 and June 2012), we have reported that patients with longer INR recall interval (4-8 weeks) showed no decrease of monitoring quality and that it would be safe to increase time between measurements. Aim: Since actual recommendations for improving TTR include shortening INR recall interval (Lip et al. 2018) we aimed to evaluate the quality of anticoagulation monitoring after having increased time between measurements beyond the 4-8 weeks recall interval. Methodology: We retrospectively analyzed 37931 appointments of 6 consecutive years (July 2012 to July 2018) corresponding to 1587 patients that are regularly followed up at an outpatient Anticoagulation Clinic of a central hospital under anticoagulation for at least 8 weeks, using TTR determined by Rosendaal method. Patients were divided according to target INR in three groups: Group 1 with target INR 2-3, including 1430 patients corresponding to 30743 appointments with mean age 69±15 years (mean±SD), majority (46.4%) with atrial fibrillation (AF); Group 2 with target INR 2.5-3.5, including 125 patients corresponding to 5439 appointments with mean age 67±12 years, majority (85.6%) with mechanical heart valves; Group 3 with target INR 3-4, including 32 patients corresponding to 1749 appointments with mean age 62±14 years, majority (62.5%) with antiphospholipid syndrome. Descriptive statistics (mean, standard deviation, minimum, maximum, chi-square), inferential statistics (t-test, A-Nova and effect sizes) tests and correlations were performed. Results: The 1587 patient population, 50.5% male, mean age of 68±17 years and 90.1% in Group 1, showed a mortality of 18%. A point-biserial correlation was run to determine the relationship between mortality and gender, age, INR group and diagnostic. Mortality was correlated with diagnosis (57.2% with AF) (rpb = -.071, n = 1587, p = .004), male gender (60%) (rpb = -.089, n = 1587, p <.001) and age (75±12) (rpb = .175, n= 1587, p<.001) but not with INR group (rpb = -.017, n = 1587, p = .499). Indeed, between groups mortality was not different [Χ2(2)=.492; p=.782; φ=.018] nor mean age [F(2, 1584)=2.588; p=.078; η2=.003], but gender distribution was unequal [Χ2(2)= 10.815; p=.004; φ=.083] with male predominating in Group 1 (51.9%) and female in Group 2 (60.8%) and 3 (65.6%). Patients in Group 1, corresponding to 90.1% of the total population, had TTR of 72%, patients in Group 2 had TTR of 69% and patients in Group 3 had TTR of 60%. Comparatively to the previous study (2006-2012), we noticed a significant decrease in patient population / appointments size (2087/ 61988) (p <.001) with a decrease of TTR in Group 1 (1927 patients) (83%) and Group 2 (120 patients) (74%) but a TTR increase in Group 3 (40 patients) (54%) (p <.001). Conclusions and Discussion: More than 90% of the population under VKA treatment showed effective TTR which may infer safety in increasing INR recall interval. The TTR decrease with a smaller population may be explained by the introduction of direct oral anticoagulants in patients with less comorbidities. The increase of TTR in patients with higher INR target suggests a better management of patients under VKA therapy that is actually the only choice for challenging patients. Disclosures No relevant conflicts of interest to declare.

Quality control of oral anticoagulation with vitamin K antagonists in primary care patients in Poland: a multi-centre study.

Vitamin K antagonists (VKAs) remain the mainstay of anticoagulation therapy, which requires monitoring of international normalised ratio (INR). Quality of oral anticoagulation, clinical benefits, and the risk related to VKA use are determined by the time in therapeutic range (TTR). The aim of this study was to assess the therapeutic quality of oral anticoagulation and to determine the factors that affect the incidence of INR outside the recommended range in primary care patients undergoing long-term VKA therapy in Poland. A multi-centre cross-sectional analysis was carried out in 15 general practices from three voivodeships of Poland. At the planned time, INRs measured closest to the designated date in all patients were assessed in terms of being within the therapeutic range. TTR was determined as the percentage of visits with INR in therapeutic range on a given date. Overall, 430 patients aged 70.3 ± 12.7 years (222 men aged 72 ± 12.8 years and 208 women aged 68.5 ± 12.4 years) were included in the study. In the groups with INR below, within, and above therapeutic range, the patients' age was 67.3 ± 13.4, 72 ± 12, and 70.5 ± 13 years (p = 0.001), respectively. TTR for all the participants was 55%. Statistically significant factors associated with INRs outside the therapeutic range were: age below 60 years (compared to older persons; p = 0.003), more or less frequent INR control compared to the recommended intervals of four to eight weeks (p < 0.001), and the type of the VKA used, i.e. acenocoumarol compared to warfarin (p < 0.001). Logarithmic regression analysis showed that the use of acenocoumarol compared to warfarin, increased the chances of INRs below therapeutic range (odds ratio [OR] 3.19; 95% confidence interval [Cl] 1.65-6.16), while male sex increased the probability of INR being above this range (OR 2.01; 95% Cl 1.12- 3.59). The TTR in primary care patients on VKA therapy was 55%. Better quality of oral anticoagulation with VKA could be achieved by using warfarin instead of acenocoumarol, proper INR monitoring in the recommended interval of four to eight weeks, and tighter INR control in younger and male patients.

Quality of oral anticoagulation with vitamin K antagonists in 'real-world' patients with atrial fibrillation: a report from the prospective multicentre FANTASIIA registry.

The efficacy and safety of oral anticoagulation (OAC) using the vitamin K antagonists (VKA) are closely associated with the quality of anticoagulation, reflected by time in therapeutic range (TTR). The SAMe-TT2R2 is a risk score developed to predict the quality of anticoagulation control among VKA users. To analyse the quality of anticoagulation and its clinical determinants based on different methods in a prospective cohort of atrial fibrillation patients on VKA treatment participating in the multicentre Spanish observational registry FANTASIIA. Estimated TTR was calculated from Rosendaal, direct method, international normalized ratio variability, and NICE criteria. Time in therapeutic range values were compared for those patients with a SAMe-TT2R2 score 0-2 and >2. One thousand four hundred and seventy patients were analysed (56.4% male, mean age 74.1 ± 9.5 years). Mean TTR was 61.5 ± 25.1 with Rosendaal and 64.7 ± 24.2 with direct method. There was a high correlation between both methods (ρ = 0.805). The prevalence of poor anticoagulation control was 55%. Diabetes mellitus [odds ratio (OR) 1.38; P = 0.008], peripheral artery disease (PAD, OR 1.62; P = 0.048), and HAS-BLED (OR 1.13; P = 0.022) were independently associated with TTR < 70%. SAMe-TT2R2 score 0-2 had a higher mean TTR than patients with SAMe-TT2R2 >2 (P = 0.044), with a specificity of > 90% for predicting TTR < 70%. Patients with TTR < 70% had higher risk of events (21.7 vs. 16.8%; P = 0.021). In a multicentre prospective registry, 55% of AF patients had poor anticoagulation control with diabetes mellitus, PAD, and HAS-BLED being independently associated with TTR < 70%. A high SAMe-TT2R2 scores had a high specificity for predicting a TTR < 70% as an indicator of poor quality anticoagulation.

Quality of oral anticoagulation with phenprocoumon in regular medical care and its potential for improvement in a telemedicine-based coagulation service--results from the prospective, multi-center, observational cohort study thrombEVAL.

BackgroundThe majority of studies on quality of oral anticoagulation (OAC) therapy with vitamin K-antagonists are performed with short-acting warfarin. Data on long-acting phenprocoumon, which is frequently used in Europe for OAC therapy and is considered to enable more stable therapy adjustment, are scarce. In this study, we aimed to assess quality of OAC therapy with phenprocoumon in regular medical care and to evaluate its potential for optimization in a telemedicine-based coagulation service.MethodsIn the prospective observational cohort study program thrombEVAL we investigated 2,011 patients from regular medical care in a multi-center cohort study and 760 patients from a telemedicine-based coagulation service in a single-center cohort study. Data were obtained from self-reported data, computer-assisted personal interviews, and laboratory measurements according to standard operating procedures with detailed quality control. Time in therapeutic range (TTR) was calculated by linear interpolation method to assess quality of OAC therapy. Study monitoring was carried out by an independent institution.ResultsOverall, 15,377 treatment years and 48,955 international normalized ratio (INR) measurements were analyzed. Quality of anticoagulation, as measured by median TTR, was 66.3% (inte rquartile range (IQR) 47.8/81.9) in regular medical care and 75.5% (IQR 64.2/84.4) in the coagulation service (P <0.001). Stable anticoagulation control within therapeutic range was achieved in 63.8% of patients in regular medical care with TTR at 72.1% (IQR 58.3/84.7) as compared to 96.4% of patients in the coagulation service with TTR at 76.2% [(IQR 65.6/84.7); P = 0.001)]. Prospective follow-up of coagulation service patients with pretreatment in regular medical care showed an improvement of the TTR from 66.2% (IQR 49.0/83.6) to 74.5% (IQR 62.9/84.2; P <0.0001) in the coagulation service. Treatment in the coagulation service contributed to an optimization of the profile of time outside therapeutic range, a 2.2-fold increase of stabile INR adjustment and a significant decrease in TTR variability by 36% (P <0.001).ConclusionsQuality of anticoagulation with phenprocoumon was comparably high in this real-world sample of regular medical care. Treatment in a telemedicine-based coagulation service substantially improved quality of OAC therapy with regard to TTR level, frequency of stable anticoagulation control, and TTR variability.Trial registrationClinicalTrials.gov, unique identifier NCT01809015, March 8, 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0268-9) contains supplementary material, which is available to authorized users.

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.

Letter by Stöllberger et al Regarding Article, “Stroke Risk and Antithrombotic Strategies in Atrial Fibrillation”

HomeStrokeVol. 42, No. 4Letter by Stöllberger et al Regarding Article, “Stroke Risk and Antithrombotic Strategies in Atrial Fibrillation” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Stöllberger et al Regarding Article, “Stroke Risk and Antithrombotic Strategies in Atrial Fibrillation” Claudia Stöllberger, MD, Birke Schneider, MD and Josef Finsterer, MD Claudia StöllbergerClaudia Stöllberger Search for more papers by this author , Birke SchneiderBirke Schneider Search for more papers by this author and Josef FinstererJosef Finsterer Search for more papers by this author Originally published3 Mar 2011https://doi.org/10.1161/STROKEAHA.110.609438Stroke. 2011;42:e365Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2011: Previous Version 1 To the Editor:With interest we read the article of Medi et al about stroke risk and antithrombotic strategies in atrial fibrillation.1 We have several comments on the emerging therapies to prevent stroke that are mentioned in the article: Achieving good control of international normalized ratio (INR) values is a matter of concern in patients undergoing therapy with vitamin K antagonists. A subanalysis of the ACTIVE trial has shown that considerable national differences exist in the quality of oral anticoagulation (OAC).2 Most probably, these differences are caused by organization of the health care system and by differences in the reimbursement of physicians and institutions who take care of patients on vitamin K antagonists. Thus, an improvement in the quality of OAC is a matter of public health, and initiatives should be directed toward these institutions on national and international levels.INR self-monitoring improves the quality of OAC. Patients capable of self-monitoring therapy with vitamin K antagonists have fewer thromboembolic events, a higher proportion of INR values within the therapeutic range, and lower mortality than do patients under conventional monitoring of OAC.3 Instead of only complaining that INR values are frequently outside the therapeutic range, atrial fibrillation patients should be encouraged to perform INR self-monitoring.Whether dabigatran, rivaroxaban, or apixaban will solve the problems associated with vitamin K antagonists is uncertain. These drugs are substrates of the intestinal P-glycoprotein transport system. A variety of drugs and food components affect the P-glycoprotein system, thus influencing serum levels of these drugs. It has been shown that P-glycoprotein-affecting drugs are prescribed to 42% of hospitalized atrial fibrillation patients.4 The relevance of these drug and food interactions are unknown. There is an urgent need to collect data on this issue, a task that will be impeded by the lack of easily available laboratory testing of antithrombotic effects.Furthermore, the long-term effects of thrombin-generation inhibition are unknown. Thrombin plays an important role in infection, immune response, angiogenesis, tumor growth, and endothelial function. Reported adverse effects of new antithrombotic drugs were restricted to hemorrhagic, gastrointestinal, and vascular events; however, they did not consider conditions like cancer, sepsis, or infection. Furthermore, in the RE-LY study, dabigatran was discontinued in 21% of the patients after 2 years. Which alternative therapy should these patients receive?Occlusion of the left atrial appendage (LAA), as stressed by the authors, has a high procedural complication rate and an uncertain long-term effect.1 Because of the high compliance of the LAA myocardium, leaks between the wall and the occluder may develop months, or even years, after occluder implantation, and may be a new source of embolism.5 Furthermore, the LAA protects the left ventricle from pressure and volume overload. The long-term consequences of LAA-occlusion or resection on cardiac function and on the development of heart failure are largely unknown.From these considerations, we conclude that stroke prevention in atrial fibrillation should be directed primarily toward improving the quality of standard OAC by enhancing INR self-monitoring as well as initiatives in public health. Whether new antithrombotic drugs are useful for stroke prevention outside randomized clinical trials is still uncertain. There is an urgent need to assess the relevance of drug and food interactions and potential adverse effects of these drugs. LAA occlusion is an experimental procedure of yet unproven benefit, carries potential risk, and thus should not be performed until all open questions have been answered.Claudia Stöllberger, MDBirke Schneider, MDJosef Finsterer, MD RudolfstiftungWien Österreich and Sana Kliniken medizinische Klinik II Lübeck, DeutschlandFootnotesStroke welcomes Letters to the Editor and will publish them, if suitable, as space permits. Letters must reference a Stroke published-ahead-of-print article or an article printed within the past 3 weeks. The maximum length is 750 words including no more than 5 references and 3 authors. Please submit letters typed double-spaced. Letters may be shortened or edited. Include a completed copyright transfer agreement form (available online at http://stroke.ahajournals.org and http://submit-stroke.ahajournals.org).

The Belgian Improvement Study in Oral Anticoagulant Therapy: a randomized clinical trial

We read with great interest the article by Claes et al . about The Belgian Improvement Study on Oral Anticoagulant Therapy. The randomized clinical trial compares different interventional models to improve the quality of oral anticoagulant therapy in general practitioners' (GP's) practice who mainly manage the control of anticoagulation.1 In Hungary, arterial and venous vessel diseases have a great impact on morbidity and mortality data, so the quality of oral anticoagulation is essential. Last year, we published a retrospective survey …

Quality of oral anticoagulation in patients with atrial fibrillation: A cross-sectional study in general practice

Objective: To evaluate the quality of management of oral anticoagulation among patients on oral anticoagulation for atrial fibrillation, and to verify the relation between patient performance and the risk of an event due to therapy. Methods: In a retrospective cross-sectional study involving 66 general practices, international normalized ratio (INR) values obtained over a 6-mo period were analysed. All INR values were determined by a single clinical laboratory, and additional medical information was provided by GPs. Results: 395 patients were included in the study, with a mean age of 74±9.6 y. In total, 3111 INR values were obtained. The mean number of tests/month per patient was 2.7±4.3. A total of 49 728 d of therapy was evaluated. Fifty-three per cent of the day values were within 0.5 INR units of the target (and 69% within 0.75 INR units of the target). The incidence rate for major bleeding was 4.4/100 patient years (and 2.9/100 patient years for thromboembolic events). There was a significant relation between patient performance and the presence of an event (p=0.017), with an odds ratio of 2.8 (95% CI 1.3–6.3).Conclusion: The quality of oral anticoagulation in patients with atrial fibrillation is suboptimal. This is significantly related to an increased risk of haemorrhagic events.

INR-Selbstmanagement nach mechanischem Herzklappenersatz: ESCAT (Early Self-Controlled Anticoagulation Trial)

Severe thromboembolic and hemorrhagic complications following mechanical heart valve replacement essentially occur due to intense oral anticoagulation and fluctuating individual INR values around the target range. INR self-management can help to minimize these fluctuations. Beginning this therapeutic control immediately after mechanical heart valve replacement further reduces anticoagulant-induced complications. Included in the study were 1200 patients. The quality of oral anticoagulation also improved through INR self-management. Over an observation period of two years, nearly 80 % of INR values recorded by the patients themselves were within the target therapeutic range of 2.5-4.5. This corresponds to a high significance of p < = 0.001 in favor of INR self-management. Only 64.9 % of INR values monitored by family practitioners were within the desired range. The results differed slightly in quality between patient groups with different levels of training (comprehensive, secondary modern, grammar with or without university). Of patients trained in INR self-management following mechanical heart valve replacement, 91.7 % maintained their competence in this technique throughout the entire follow-up period. Only 8.3 % of those trained immediately after surgery were unable to continue with INR self-management.

Comparison between Recombinant and Rabbit Thromboplastin in the Management of Patients on Oral Anticoagulant Therapy

The aim of this study was to compare recombinant thromboplastin (rTF, ISI = 0.82) with rabbit thromboplastin (RT, ISI = 1.46) in order to evaluate which performed better in our thrombosis centre. To this purpose we randomized 67 patients to be double-blind monitored in two groups for three months either with PT performed with RT or with PT performed with rTF. After this period each patient was shifted to the other group. We considered the following as end points of the study: percentages of PT results within the therapeutic range, number of visits and therapeutic dose adjustments per patient. The "last check in file" method was used to evaluate the laboratory quality of oral anticoagulation for both thromboplastins. The results show that there was no difference in the number of visits per patient between the two groups: 6.9 +/- 1.7 in the rTF group versus 7.3 +/- 1.9 in the RT group (p = 0.19). The variations of therapeutic dose per patient were not different in the two groups: the dose was changed once (range 0-8) in the rTF group and once (range 0-11) in the RT group (p = 0.15). The percentages of PT results within the therapeutic range were not different between the two groups. The "last check in file" method showed similar percentages in both groups: PT results in the therapeutic range were 67.2% in the RT group and 68.8% in the rTF group. We conclude that the two thromboplastins had a similar effect on the end points of the study in spite of the relatively high ISI of the RT.

Recombinant Versus High-sensitivity Conventional Thromboplastin: A Randomized Clinical Study in Patients on Oral Anticoagulation

A prospective, randomized, double-blind clinical trial was carried out in a single center to compare the clinical and laboratory quality of oral anticoagulant therapy monitored with recombinant tissue factor (RTF) or with a sensitive, human-derived, conventional thromboplastin (CT) in the PT test. Seven hundred and fifty-seven consecutive patients receiving oral anticoagulation for various indications were randomized to RTF (n = 379) or CT (n = 368) for 6 months. Total follow-up was 167 and 153 patient-years for RTF and TP groups respectively. Fifty-six bleeding events were observed: 31 in the RTF group and 25 in the TP group. The incidence of bleeding was 18.5 and 16.5% pt-yrs for RTF and TP patients respectively (n.s.). The event-free follow-up curves were not significantly different between the two groups. The laboratory quality of oral anticoagulation was evaluated with the "last check in file" method: therapeutic INR was found in the same proportion of RTF and TP patients (70.2% vs 68.8%). Our study shows that RTF is as effective as a sensitive, conventional thromboplastin for monitoring oral anticoagulation.

Progress in the Control of Oral Anticoagulation

SummaryIt should be realized that the quality of oral anticoagulation depends on thorough pharmacological knowledge of coumarin congeners, skilled clinical supervision of the patient and well-standardized laboratory control of patients’ blood. Results of the laboratory control should no longer be expressed in terms of conventional prolongation ratios or percentages only. Exact data as to laboratory standardization with reference plasmas and the results of translation into terms of reference thromboplastins have to be given.