The patterns of anticoagulation control and the risk of stroke,bleeding and mortality in patients with non‐valvular atrial fibrillation

Summary. Background: Anticoagulation control is often summarized using the percentage of time spent in a therapeutic range (TTR). This method does not describe the timing and severity of fluctuations in the International Normalised Ratio (INR).Objective: To evaluate whether the TTR method can be improved by considering the patterns of INR over time.Methods: The cohort included adults aged 40+ years with atrial fibrillation (AF) and laboratory records of INR as recorded in the UK Clinical Practice Research Datalink. Statistical clustering techniques based on simple INR measures were used to describe the patterns of INR. Nested case–control studies calculated the odds ratios (ORs) for the risk of stroke, bleeding and mortality with TTR and different INR patterns. It was also evaluated whether cluster analyses improved the prediction of outcomes over TTR.Results: A number of 27 381 patients were studied with a mean age of 73 years. The OR for mortality was 3.76 (95% confidence interval [CI] 3.03–4.68) in patients with < 30% TTR compared with patients with 100% TTR. INR patterns were found to be best described by six different clusters. The cluster with the most unstable pattern was associated with the largest risk of mortality (OR 10.7, 95% CI 8.27–13.85) and stroke (OR 3.42, 95% CI 2.08–5.63). INR measures that predicted death independent of the TTR‐included absolute difference between two subsequent INR measurements and change relative to the mean over time.Conclusion: Cluster analysis of INR patterns improved the prediction of clinical outcomes over TTR and may help to identify warfarin users who need additional anticoagulation monitoring.     

Anticoagulation for stroke prevention in elderly patients with atrial fibrillation,including those with falls and/or early-stage dementia: A single-center,retrospective, observational study

Background: Anticoagulation for stroke prevention is underused in elderly patients with nonvalvular atrial fibrillation (AF). Those with falls and/or early dementia may be at particular risk for stroke and hemorrhage.Objective: The aim of this study was to determine the prescribing patterns, risks, and benefits of anticoagulation with warfarin or acetylsalicylic acid (ASA) in elderly patients with AF at risk for stroke and hemorrhage, including those with falls and/or dementia.Methods: In this single-center, retrospective, observational study, data from patients aged ≥65 years with chronic nonvalvular AF treated at an urban academic geriatrics practice over a 1-year period were included. Eligible patients were receiving noninvasive management of AF with warfarin or ASA. Data were assessed to determine the prevalences of stroke, hemorrhage, falls, and the possible effects of anticoagulation with dementia. Outcomes events at 12 months, including time-in-therapeutic range (TTR), stroke, hemorrhage, and death, were determined. The stroke risk in each patient was estimated using the CHADS₂ (congestive heart failure, hypertension, age ≥75 years, diabetes, history of stroke or transient ischemic attack) score, and the risk for hemorrhage was estimated using the Outpatient Bleeding Risk Index.Results: A total of 112 patients (mean age, 82 years) were identified; 106 were included in the present analysis (80 women, 26 men); 6 were not receiving antithrombotic therapy and thus were excluded from the analysis. Warfarin was prescribed in 85% (90 patients); ASA, 15% (16). International normalized ratio testing was done frequently, with a median interval of 13.7 days between tests (92% within 28 days). No association was found between an improved TTR and the number of tests per unit of time or the number of patients per clinician. The distributions of both the CHADS₂ and Outpatient Bleeding Risk Index scores were not significantly different between the warfarin and ASA groups. The proportions of patients treated with warfarin were not significantly different between the groups with a high risk for hemorrhage and the groups at lower risk. At 12 months in the 90 patients initially treated with warfarin, the rate of stroke was 2% (2 patients); major hemorrhage, 6% (5); and death, 20% (18). Mortality was greater in patients with falls (45% [5/11]) and/or dementia (47% [8/17]) compared with those without either falls or dementia (12% [8/65]).Conclusions: In this well-monitored geriatric population with chronic AF, including patients with falls and/or dementia, a high percentage were prescribed warfarin (85%), with low rates of stroke, hemorrhage, and death at 12 months despite a low TTR. Patients with falls and/or dementia had a high mortality rate (~45%).     

INR targets and site‐level anticoagulation control: results from the Veterans AffaiRs Study to Improve Anticoagulation (VARIA)

Summary. Background: Not all clinicians target the same International Normalized Ratio (INR) for patients with a guideline‐recommended target range of 2–3. A patient’s mean INR value suggests the INR that was actually targeted. We hypothesized that sites would vary by mean INR, and that sites of care with mean values nearest to 2.5 would achieve better anticoagulation control, as measured by per cent time in therapeutic range (TTR).Objectives: To examine variations among sites in mean INR and the relationship with anticoagulation control in an integrated system of care.Patients/Methods: We studied 103 897 patients receiving oral anticoagulation with an expected INR target between 2 and 3 at 100 Veterans Health Administration (VA) sites from 1 October 2006 to 30 September 2008. Key site‐level variables were: proportion near 2.5 (that is, percentage of patients with mean INR between 2.3 and 2.7) and mean risk‐adjusted TTR.Results: Site mean INR ranged from 2.22 to 2.89; proportion near 2.5, from 30 to 64%. Sites’ proportions of patients near 2.5, below 2.3 and above 2.7 were consistent from year to year. A 10 percentage point increase in the proportion near 2.5 predicted a 3.8 percentage point increase in risk‐adjusted TTR (P < 0.001).Conclusions: Proportion of patients with mean INR near 2.5 is a site‐level ‘signature’ of care and an implicit measure of targeted INR. This proportion varies by site and is strongly associated with site‐level TTR. Our study suggests that sites wishing to improve TTR, and thereby improve patient outcomes, should avoid the explicit or implicit pursuit of non‐standard INR targets.     

超高龄心房颤动患者华法林抗凝过程中心血管不良事件的观察

目的: 观察超高龄房颤患者采用不同强度华法林抗凝后的心血管不良事件发生情况,探讨此类患者国际标准化比值(international normalized ratio,INR)的合理范围,为临床提供依据。方法: 将108例超高龄房颤患者（年龄≥80岁）按INR值分为中等强度抗凝组（56例）和低等强度抗凝组（52例）;低等强度抗凝组的INR维持在1.40~1.80;中等强度抗凝组的INR维持在1.81~2.50。随访（1.8±1.2）年,观察发生主要终点事件（缺血性卒中、全身性栓塞）、次要终点事件（非致命性心肌梗死、全因死亡联合终点）、安全性终点事件（致命性出血、严重出血和轻度出血）的情况。结果: 随访期间,中等强度抗凝组中有3例患者发生栓塞,发生率为5.36%;低等强度抗凝组中有6例发生栓塞,发生率为11.54%,均为脑卒中,2组间差异有统计学意义（P<0.05）。低等强度抗凝组中2例、中等强度抗凝组中3例患者出现眼结膜、鼻出血等不良反应,但均无严重出血,2组间出血发生率差异无统计学意义（P>0.05）。结论: 超高龄房颤患者应用华法林,INR维持在1.81~2.50是安全、有效的。     

Warfarin therapeutic monitoring: is 70% time in the therapeutic range the best we can do?

Heavier than air flying machines are impossible. Lord Kelvin, President, Royal Society of England, 1895 What is known and Objective: Warfarin, an oral anticoagulant, which has been in clinical use for over sixty years, remains a challenge for clinicians to utilize, given the multiplicity of items which can limit its efficacy. Our objective is to review the evidence and comment on whether INR control can be better than has been currently reported in various studies. Comment: The duration of time a patient’s international normalized ratio (INR) is maintained within the therapeutic range (time in the therapeutic range, TTR) for his or her particular indication for the drug impacts the effectiveness and safety of warfarin therapy. Maintaining a therapeutic INR while on warfarin is difficult, and numerous studies employing various strategies confirm the challenge, but not the impossibility of achieving a TTR above 70%. What is new and Conclusion: Maintaining a therapeutic INR requires a dedicated multi‐faceted approach. With diligence, skill and various therapeutic strategies, a TTR >70% can be achieved.     

脑梗死合并心房颤动358例抗凝治疗状况分析

目的 了解心房颤动伴脑梗死住院患者抗凝治疗的情况,并比较与指南建议之间的差距.方法 对我院2008年1月至2012年6月收治的358例脑梗死合并心房颤动患者的临床资料进行回顾性分析,重点分析抗凝药物使用情况.结果 358例患者中254例既往有心房颤动史（70.9％）,在脑梗死发病前服用过华法林者11例,占有心房颤动病史患者的4.3％;11例患者国际标准化比值（INR）均＜1.5.出院患者中,20.9％接受华法林抗凝治疗.使用华法林与HAS-BLED评分,MRS评分及抗血小板药物呈负相关（OR分别为-1.974、-0.725、-4.170,P＜0.05或P＜0.01）.出院后给予华法林治疗的患者中,33.8％长期坚持服用华法林,用药剂量中位数为2.5 mg（1.25～3.75 mg）,INR控制在1.5～3.1之间.患者平均1个月（2周～2个月）复查一次凝血常规,INR在治疗目标范围内的时间百分比平均为（61.6±21.2）％.结论 脑梗死合并心房颤动患者的抗凝治疗率和INR达标率均较低,对出血的担忧和监测INR的不便影响了华法林的使用.     

Review of antithrombotic drug usage in atrial fibrillation

Background: The important prophylactic role of antithrombotic therapy against stroke in nonrheumatic atrial fibrillation (AF) has been clearly established in recent clinical trials. There have been suggestions, however, that practice has been slow to change in light of the findings of these trials Aim: To review cases of AF at the major teaching hospital in Tasmania, Australia, to determine whether the recommendations from the results of the trials had been translated into local clinical practice Methods: A retrospective review of the medical records for consecutive patients who had AF documented on ECG between 1 January and 30 June 1997 was performed. An extensive range of demographic and clinical variables were recorded for patients with chronic or paroxysmal nonrheumatic AF. These included antithrombotic and other drug therapy at admission and discharge from hospital care, risk factors for stroke, contraindications to antithrombotic use, and incidents of ischaemic stroke and bleeding complications that occurred during the period from January 1996 up to 3 months after the hospital admission that was studied Results: The 228 patients included in the study had a mean (±SD) age of 75·3±10·9 years. Sixty-eight per cent had chronic AF and 32% had paroxysmal AF. According to two risk stratification criteria, 91% and 86% of the patients with previously diagnosed chronic or paroxysmal nonrheumatic AF ( n=186) had a high risk of developing stroke at the time of admission to hospital care. However, less than one-third of these patients were receiving warfarin (or warfarin plus aspirin), with almost another one-third receiving no antithrombotic agent. Of those who were not taking warfarin, about 60% had no apparent contraindication to warfarin. For those high risk patients who had a possible contraindication to warfarin, only approximately one-third had been prescribed aspirin. Only a slight increase in the use of antithrombotic agents had occurred by the time of discharge from hospital care. The majority of international normalized ratio (INR) values on admission for patients who had been taking warfarin were subtherapeutic. The estimated annual incidence of bleeding complications in patients taking warfarin was 15·0% overall, 5·0% for major bleeds and 3·8% for intracranial haemorrhages Conclusions: While a number of published trials have demonstrated that antithrombotic agents confer substantial protection against stroke in patients with nonrheumatic AF, the drugs were underused in our setting. There is a need to improve antithrombotic use and to develop a better monitoring system for the provision of safer and more effective antithrombotic therapy.     

Stroke risk assessment for atrial fibrillation: hospital-based stroke risk assessment and intervention program

Background: Despite the proven effectiveness of antithrombotic therapy for atrial fibrillation (AF), the treatment remains suboptimal. The aim of this study was to implement and evaluate a system to improve the appropriate use of antithrombotics for stroke prevention in AF utilizing a clinical pharmacist as a stroke risk assessor. Method: Hospital in‐patients with AF were prospectively identified and they received a formal stroke risk assessment from a pharmacist. The patients’ risk of stroke was assessed and documented according to Australian guidelines and a recommendation regarding antithrombotic therapy was made to the medical team on a specially designed stroke risk assessment form. Results: One hundred and thirty‐four stroke risk assessments were performed during the intervention period. For those patients at high risk of stroke and with no contraindication present (warfarin‐eligible patients), 98% were receiving warfarin on discharge from hospital compared to 74% on admission (P < 0·001). Of the 50 (37%) assessments that recommended a change of therapy, 44 (88%) resulted in a change in the patient’s current antithrombotic therapy compared to their admission therapy. Thirty (68%) of the assessments resulted in an ‘upgrade’ to more‐effective treatment options for example from no therapy to any agent or from aspirin to warfarin. Discussion and Conclusion: The pharmacist‐led stroke risk assessment program resulted in a significant increase in the proportion of patients receiving appropriate thromboprophylaxis for stroke prevention in AF. The methods used in this study should be evaluated in a larger trial, in multiple hospitals, with different pharmacists performing the intervention.     

Warfarin dose management affects INR control

Summary.  Background:  Little is known about how patterns of warfarin dose management contribute to percentage time in the therapeutic International Normalized Ratio (INR) range (TTR). Objectives:  To quantify the contribution of warfarin dose management to TTR and to define an optimal dose management strategy. Patients/methods:  We enrolled 3961 patients receiving warfarin from 94 community-based clinics. We derived and validated a model for the probability of a warfarin dose change under various conditions. For each patient, we computed an observed minus expected (O − E) score, comparing the number of dose changes predicted by our model to the number of changes observed. We examined the ability of O − E scores to predict TTR, and simulated various dose management strategies in the context of our model. Results:  Patients were observed for a mean of 15.2 months. Patients who deviated the least from the predicted number of dose changes achieved the best INR control (mean TTR 70.1% unadjusted); patients with greater deviations had lower TTR (65.8% and 62.0% for fewer and more dose changes respectively, Bonferroni-adjusted P  < 0.05/3 for both comparisons). On average, clinicians in our study changed the dose when the INR was 1.8 or lower/3.2 or higher (mean TTR: 68%); optimal management would have been to change the dose when the INR was 1.7 or lower/3.3 or higher (predicted TTR: 74%). Conclusions:  Our observational study suggests that INR control could be improved considerably by changing the warfarin dose only when the INR is 1.7 or lower/3.3 or higher. This should be confirmed in a randomized trial.     

Efficacy of Warfarin Anticoagulation and Incident Dementia in a Community-Based Cohort of Atrial Fibrillation

Objective

To study the association between time in therapeutic range (TTR) during warfarin therapy and risk of dementia in a population-based cohort of incident atrial fibrillation (AF).

Performance outcomes of a pharmacist‐managed anticoagulation clinic in the rural,resource‐constrained setting of Eldoret,Kenya

Summary. Background: It is recommended that warfarin therapy should be managed through an anticoagulation monitoring service to minimize the risk of bleeding and subsequent thromboembolic events. There are few studies in Sub‐Saharan Africa that describe warfarin management in spite of the high incidence of venous thromboembolism (VTE) and rheumatic heart disease. Objective: To examine the feasibility of the Moi Teaching and Referral Hospital anticoagulation monitoring service and compare its performance with clinics in resource‐rich settings. Methods: A retrospective chart review compared the percentage time in the therapeutic range (TTR) and rates of bleeding and thromboembolic events to published performance targets using the inference on proportions test. Wilcoxon’s rank sum analyses were used to establish predictors of TTR. Results: For the 178 patients enrolled, the mean TTR was 64.6% whereas the rates of major bleeds and thromboembolic events per year were 1.25% and 5%, respectively. In the primary analysis, no statistically significant differences were found between the results of TTR, major bleeds and thromboembolic events for the clinic and published performance rates. In the secondary analysis, having an artificial heart valve and a duration of follow‐up of > 120 days were positively associated with a higher TTR (P < 0.05) whereas venous thromboembolism, history of tuberculosis, HIV and a duration of follow‐up of < 120 days were associated with having a lower TTR (P < 0.05). Conclusions: The performance of the MTRH anticoagulation clinic is non‐inferior to published metrics on the performance of clinics in resource‐rich settings.     

华法林抗凝治疗中药师干预对治疗效果及安全性的影响

目的探讨在华法林抗凝治疗中药师干预对治疗效果及用药安全性的影响。方法选择2017年1月至2017年12月服用华法林进行抗凝治疗的86例患者为对照组,以2018年1月至2018年12月由临床药师参与指导华法林抗凝治疗的86例患者为观察组。比较两组患者的治疗效果。结果观察组达到稳态时间、INR达标时间短于对照组,出院时INR达标率高于对照组(P<0.05)。观察组平均TTR大于对照组,且观察组在TTR<58%范围内的患者占比少于对照组,在TTR>70%范围内患者的占比多于对照组(P<0.05)。观察组血栓及出血总发生率均低于对照组,抗凝知识评分高于对照组(P<0.05)。结论临床药师参与华法林抗凝治疗的指导可以显著提高抗凝质量和安全性,改善患者对抗凝知识的知晓情况。     

Effect of a simple two-step warfarin dosing algorithm on anticoagulant control as measured by time in therapeutic range: a pilot study

Summary.  Background:  The efficacy and safety of vitamin K antagonists for the prevention of thromboembolism are dependent on the time for which the International Normalized Ratio (INR) is in the therapeutic range. The objective of our study was to determine the effect of introducing a simple two-step dosing algorithm, as compared with dosing by anticoagulation clinic staffs on the basis of their experience, on time in therapeutic range (TTR) of warfarin therapy. Methods:  We compared TTRs of all clinic patients before and after the introduction of a simple two-step dosing algorithm at a single anticoagulation clinic in Canada, between 1 August 2006 and 24 December 2008. TTR was calculated using the linear interpolation method of Rosendaal. Results:  We included 873 patients in the 'before' phase and 1088 patients in the 'after' phase. Introduction of the dosing algorithm significantly increased TTR of patients with a therapeutic INR range of 2–3 from 67.2% to 73.2% ( P  < 0.001), and that of patients with a therapeutic INR range of 2.5–3.5 from 49.8% to 63.8% ( P  < 0.001). Conclusions:  The introduction of a simple two-step warfarin-dosing algorithm in place of dosing by experienced anticoagulation clinic staff significantly improved mean TTR for patients in a tertiary-care anticoagulation clinic. This inexpensive and widely applicable algorithm has the potential to improve warfarin control.     

No increased bleeding events with continuation of oral anticoagulation therapy for patients undergoing cardiac device procedure

Background: Switching warfarin for heparin has been a practice for managing periprocedural anticoagulation in high‐risk patients undergoing device‐related procedures. We sought to investigate whether continuation of warfarin sodium therapy without heparin bridging is safe and, when it is continued, the optimal international normalized ratio (INR) without increased bleeding risk at time of device‐related procedure. Methods and Results: We retrospectively studied 766 consecutive patients taking warfarin long term who underwent device‐related procedures. Patients were grouped by treatment: discontinued warfarin (?warfarin, n = 243), no interruption of warfarin (+warfarin, n = 324), and discontinued warfarin with heparin bridging (+heparin, n = 199). The study primary endpoint was systemic bleeding or formation of moderate or severe pocket hematoma within 30 days of the procedure. Thirty‐one (4%) patients had bleeding events, including pocket hematoma in 29 patients. The bleeding events occurred more often for +heparin (7.0%) than ?warfarin (2.1%) or +warfarin (3.7%, P = 0.029). For +warfarin group, INR of 2.0–2.5 at time of procedure did not increase bleeding risk compared with INR less than 1.5 (3.7% vs 3.4%; P = 0.72), but INR greater than 2.5 increased the bleeding risk (10.0% vs 3.4%; P = 0.029). Concomitant aspirin use with warfarin significantly increased bleeding risk than warfarin alone (5.6% vs 1.4%, P = 0.02). Median length of hospitalization was significantly shorter for +warfarin than +heparin (1 vs 6 days; P < 0.001). Conclusion: Continuation of oral anticoagulation therapy with an INR level of <2.5 does not impose increased risk of bleeding for device‐related procedures, although precaution is necessary to avoid supratherapeutic anticoagulation levels. (PACE 2011; 34:868–874)     

ATRIAL FIBRILLATION IN THE ELDERLY: PHYSICIANS' ATTITUDES TO ANTICOAGULATION

SUMMARY The use of warfarin and aspirin for the primary prevention of stroke in elderly patients with atrial fibrillation (AF) is controversial. To establish current practice we circulated a questionnaire to 300 geriatricians (G) and 300 cardiologists (C). The response rates were 47% G and 51% C. Most physicians prescribed warfarin in AF associated with mitral stenosis (G vs C, 86% vs 89%, NS). Cardiologists were more likely to prescribe warfarin in AF associated with dilated cardiomyopathy (G vs C, 52% vs 86%, P<0.01). A minority would prescribe warfarin in aortic valve disease and AF (G vs C, 37% vs 24%, P<0.05) and lone AF (G vs C, 10% vs 26%, P<0.01). Aspirin was favoured in aortic valve disease and lone AF. The cardiologists were less reluctant to use warfarin in the young and more likely to electrically cardiovert the young with chronic AF.     

Patient characteristics associated with oral anticoagulation control: results of the Veterans AffaiRs Study to Improve Anticoagulation (VARIA)

Summary. Background: In patients receiving oral anticoagulation, improved control can reduce adverse outcomes such as stroke and major hemorrhage. However, little is known about patient‐level predictors of anticoagulation control. Objectives: To identify patient‐level predictors of oral anticoagulation control in the outpatient setting. Patients/Methods: We studied 124 619 patients who received oral anticoagulation from the Veterans Health Administration from October 2006 to September 2008. The outcome was anticoagulation control, summarized using percentage of time in therapeutic International Normalized Ratio range (TTR). Data were divided into inception (first 6 months of therapy; 39 447 patients) and experienced (any time thereafter; 104 505 patients). Patient‐level predictors of TTR were examined by multivariable regression. Results: Mean TTRs were 48% for inception management and 61% for experienced management. During inception, important predictors of TTR included hospitalizations (the expected TTR was 7.3% lower for those with two or more hospitalizations than for the non‐hospitalized), receipt of more medications (16 or more medications predicted a 4.3% lower than for patients with 0–7 medications), alcohol abuse (? 4.6%), cancer (? 3.1%), and bipolar disorder (? 2.9%). During the experienced period, important predictors of TTR included hospitalizations (four or more hospitalizations predicted 9.4% lower TTR), more medications (16 or more medications predicted 5.1% lower TTR), alcohol abuse (? 5.4%), female sex (? 2.9%), cancer (? 2.7%), dementia (? 2.6%), non‐alcohol substance abuse (? 2.4%), and chronic liver disease (? 2.3%). Conclusions: Some patients receiving oral anticoagulation therapy are more challenging to maintain within the therapeutic range than others. Our findings can be used to identify patients who require closer attention or innovative management strategies to maximize benefit and minimize harm from oral anticoagulation therapy.     

Risk of post‐thrombotic syndrome after subtherapeutic warfarin anticoagulation for a first unprovoked deep vein thrombosis: results from the REVERSE study

Summary. Background: Risk factors for post‐thrombotic syndrome (PTS) remain poorly understood. Objectives: In this multinational multicenter study, we evaluated whether subtherapeutic warfarin anticoagulation was associated with the development of PTS. Methods: Patients with a first unprovoked deep venous thrombosis (DVT) received standard anticoagulation for 5–7 months and were then assessed for PTS. The time in the therapeutic range was calculated from the international normalized ratio (INR) data. An INR below 2, more than 20% of the time, was considered as subtherapeutic anticoagulation. Results: Of the 349 patients enrolled, 97 (28%) developed PTS. The overall frequency of PTS in patients with subtherapeutic anticoagulation was 33.5%, compared with 21.6% in those with an INR below two for ≤ 20% of the time (P = 0.01). During the first 3 months of therapy, the odds ratio (OR) for developing PTS if a patient had subtherapeutic anticoagulation was 1.78 (95% confidence interval [CI] 1.10–2.87). After adjusting for confounding variables, the OR was 1.84 (95% CI 1.13–3.01). Corresponding ORs for the full period of anticoagulation were 1.83 (95% CI 1.14–3.00) [crude] and 1.88 (95% CI 1.15–3.07) [adjusted]. Conclusion: Subtherapeutic warfarin anticoagulation after a first unprovoked DVT was significantly associated with the development of PTS.     

Warfarin use and the risk of valvular calcification

Summary. Background: Warfarin affects the synthesis and function of the matrix Gla‐protein, a vitamin K‐dependent protein, which is a potent inhibitor of tissue calcification. Objectives: To investigate the incidence of mitral valve calcium (MVC), mitral annular calcium (MAC) and aortic valve calcium (AVC) in patients with non‐valvular atrial fibrillation (AF) treated with warfarin vs. no warfarin. Patients and methods: Of 1155 patients, mean age 74 years, with AF, 725 (63%) were treated with warfarin and 430 (37%) without warfarin. The incidence of MVC, MAC and AVC was investigated in these 1155 patients with two‐dimensional echocardiograms. Unadjusted logistic regression analysis was conducted to examine the association between the use of warfarin and the incidence of MVC, MAC or AVC. Logistic regression analyses were also conducted to investigate whether the relationship stands after adjustment for confounding risk factors such as age, sex, race, ejection fraction, smoking, hypertension, diabetes, dyslipidemia, coronary artery disease (CAD), glomerular filtration rate, calcium, phosphorus, calcium‐phosphorus product, alkaline phosphatase, use of aspirin, beta blockers, angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers, and statins. Results: There was a significant association between the use of warfarin and the risk of calcification [unadjusted odds ratio = 1.71, 95% CI = (1.34–2.18)]. The association still stands after adjustment for confounding risk factors. MVC, MAC or AVC was present in 473 of 725 patients (65%) on warfarin vs. 225 of 430 patients (52%) not on warfarin (P < 0.0001). Whether this is a causal relationship remains unknown. Conclusions: Use of warfarin in patients with AF is associated with an increased prevalence of MVC, MAC or AVC.     

Clinical manifestations and outcomes of severe warfarin overanticoagulation: from the EWA study

Introduction: Severe warfarin overanticoagulation is a risk factor for bleeding, but there is little information on its manifestations, prognosis and factors affecting the outcome. We describe the manifestations and clinical outcomes of severe warfarin overanticoagulation in a large group of patients with atrial fibrillation (AF).

Material and methods: All international normalized ratio (INR) samples (n?=?961,431) in the Turku University Hospital region between 2003 and 2015 were screened. A total of 412?AF patients with INR ≥9 were compared to 405 patients with stable warfarin anticoagulation for AF. Electronic patient records were manually reviewed to collect comprehensive data.

Results: Of the 412 patients with INR ≥9, bleeding was the primary manifestation in 105 (25.5%). Non-bleeding symptoms were recorded in 165 (40.0%) patients and 142 (34.5%) had no symptoms. A total of 17 (16.2%) patients with a bleed and 67 (21.8%) without bleeding died within 30 days after the event. Intracranial haemorrhage strongly predicted death within 30 days. Other significant predictors were non-bleeding symptoms, active malignancies, recent bleed, history of myocardial infarction, older age, renal dysfunction and a recent treatment episode.

Conclusions: Bleeds are not the major determinant of the poor prognosis in severe overanticoagulation, as coincidental INR ≥9 findings also associate with high mortality.

• KEY MESSAGES

• Only a quarter of AF patients with INR ≥9 suffered a bleeding event and the clinical manifestation of INR ≥9 had a significant impact on patient outcome.

• The 30-day mortality rate in patients with INR ≥9 was high ranging from 9.2 to 32.7%.

• Several significant predictors of 30-day mortality after INR ≥9 were identified.