Indications For Anticoagulant Therapy Research Articles

NOAC Therapy Is Also Effective and Safe in Patients Older Than 80 Years — Results of the Prospective Dresden NOAC Registry (NCT01588119)

Background: Non-vitamin-K-antagonist oral anticoagulants (NOACs) have rapidly become a cornerstone in anticoagulant therapy. However, anticoagulated patients older than 80 years represent an especially challenging population, since their thromboembolic and bleeding risks are excessively high and chronic kidney disease is common, making treatment decisions even more complicated. As a consequence, long-term safety data for this specific population are needed.Patients and methods: Using data from DRESDEN NOAC, a prospective regional registry in Germany in which patients with oral anticoagulation undergo prospective follow-up (FU) by quarterly phone interviews, we assessed rates of thromboembolic and bleeding outcomes in patients older than 80 years, based on centrally adjudicated events using standard outcome definitions.Results: Until 30th November 2017, 3984 patients were enrolled into the registry (53% male, mean age 70.2 years), including 935 patients aged ≥ 80 years (487 [52.1%] received rivaroxaban, 198 [21.2%] apixaban, 165 [17.6%] edoxaban and 85 [9.1%] dabigatran, respectively). Indication for anticoagulant therapy was atrial fibrillation (AF) in 752 (80.4%) cases, venous thromboembolism (VTE) in 179 (19.1%), and other indications in 4 (0.4%) cases. This subset of patients had a mean age of 84.2 years (range 80-100y) and 406 (43.4%) patients were male (Table 1).During a mean follow-up of 970.7 ± 642.2 days (mean NOAC exposure 815.3 ± 644.5 days) an intention-to-treat (all events counted) analysis of all very old patients demonstrated an event rate for the composite endpoint of stroke, TIA, systemic embolism or VTE of 1.0/100 patient-years (95% CI 0.8 - 1.2). In AF patients, the rate for stroke, TIA, systemic embolism was 1.0/100 patient-years (95% CI 0.8 - 1.2) and in VTE patients, the rate for recurrent DVT or PE in VTE patients was 0.4/100 patient-years (95% CI 0.2 - 0.7).In the on-treatment analysis (only on-treatment events counted), the corresponding event rates were 0.7/100 patient-years (95% CI 0.5 - 0.9) for the composite endpoint, 0.7/100 patient-years (95% CI 0.5 - 0.9) for stroke, TIA, systemic embolism in AF patients, and 0.1/100 patient-years (95% CI 0.01 - 0.3) for recurrent VTE in VTE patients, respectively. The overall rate of ISTH major bleeding was 1.0/100 patient-years (95% CI 0.8 - 1.2), with numerically higher rates in SPAF patients (1.2/100 patient-years; 95% CI 0.9 - 1.5) compared to VTE patients (0.4/100 patient-years; 95% CI 0.2 - 0.7).255 patients died during FU (2.2/100 patient-years; 95% CI 2.0 - 2.5), of which 120 deaths occurred during or within 3 days after last intake of NOAC (1.3/100 patient-years; 95% CI 1.1 - 1.6). Most common causes of death were fatal cardiovascular event (n= 86; consisting of 20 cases of acute coronary syndrome, 19 ischaemic strokes, 17 VTE, 2 systemic embolism and 123 cases of other cardiovascular deaths such as worsening of chronic heart failure, or unexplained deaths ruled as potentially related to cardiovascular events) and age related death (n= 79), followed by sepsis/infection (n= 40), terminal malignant disease (n= 26), fatal bleeding (n= 11) and other causes (n= 13).Overall, after 1800 days of FU, approximately 80% of this very old population were outcome-free survivors, as indicated by the Kaplan Meier curve (figure1).Conclusions: During long-term FU of more than 2.5 years, this very old population of NOAC recipients demonstrated low rates of cardiovascular or major bleeding complications during active NOAC therapy. Approximately one quarter of the study population died during follow-up, with cardiovascular events being the leading cause of death. Only 11 fatal bleeding events were observed; however, most of the 58 fatal thromboembolic events occurred after anticoagulation was discontinued. This indicates that continued anticoagulation with NOACs may result in a beneficial risk-benefit ratio also in very old patients. [Display omitted] DisclosuresBeyer-Westendorf:Bayer: Honoraria, Research Funding; Boehringer-Ingelheim: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding. Marten:Bayer: Honoraria; Daiichi Sankyo: Honoraria.

Anticoagulant therapies for acute venous thromboembolism: a comparison between those discharged directly from the emergency department versus hospital in two Canadian cities

ObjectiveTo compare the characteristics/management of acute venous thromboembolism (VTE) for patients either discharged directly from the emergency department (ED) or hospitalised throughout a year within two urban cities in Canada.DesignRetrospective...

Identifying patients likely to be referred for a clinical pharmacist intervention in a family medicine residency‐training clinic

IntroductionLittle is known about patient populations within family medicine residency‐training clinics that should be targeted for clinical pharmacy interventions. The objective of this study was to identify patient characteristics associated with receiving an intervention by a clinical pharmacist.MethodsThis retrospective cohort study included 4870 patients aged 40 to 89 years with at least one office visit at the University of Colorado AF Williams Family Medicine clinic from August 1, 2014 to July 31, 2015. Electronic health record data were used to examine associations between 23 previously identified patient‐specific elements and receipt of a clinical pharmacist intervention. Presence of a clinical pharmacist consultation note in the patient's record in the past 12 months was evidence of an intervention. Multivariable logistic regression was used to estimate adjusted odds ratios.ResultsFour percent (n = 182) of patients received at least one clinical pharmacist intervention. Multivariable logistic regression indicated that ≥10 active medications, A1c ≥ 9%, hypertension, depression/anxiety/panic disorder, asthma, indication for anticoagulant therapy, hospitalization/emergency department visit in the last 30 days, age ≥ 65, and Medicaid/uninsured increased the likelihood of receiving a clinical pharmacist intervention, while non‐English speaking significantly decreased the likelihood of receiving a clinical pharmacist intervention. Patients with 7 or more elements were seven times more likely to have a clinical pharmacist intervention than patients with 6 or fewer items (odds ratio = 7.0, 95% confidence interval = 5.2‐9.5).ConclusionsPatients with more elements were more likely to have received a clinical pharmacist intervention. The accumulation of these elements could be used for targeted population‐based clinical pharmacist activities in residency training clinics.

Non tumoral portal vein thrombosis during cirrhosis: Should anticoagulation be proposed?

Background: Portal vein thrombosis (PVT) is considered as infrequent and pejorative event in cirrhosis. Up to date, many questions remain about therapeutic management. Aim: The objectives of this study were to assess the impact of the PVT on the progression of liver disease, to review the indications for anticoagulation and its repercussions. Materials and methods: A case-control study was conducted over a period of 12 years (2002-2013). It included 484 cases of cirrhosis. Among these patients, 41 had non tumoral portal vein thrombosis (case group). The control group included the remaining 443 patients. Results: In our study, there was no impact of PVT on the natural history of cirrhosis both in terms of complications or survival. Only the early introduction of anticoagulant therapy was associated with a re-permeabilization of portal vein at one year (OR1.6; 95% CI [1.10-2.01]). Prolonged anticoagulation was inversely correlated with recurrent PVT after treatment. However, obtaining a portal vein re-permeabilization was not correlated to a significant gain in terms of prevention of complication related to cirrhosis and survival. Conclusions: results suggest that portal vein thrombosis in patients with cirrhosis is not a formal indication for anticoagulant therapy. It should be reserved for candidates of liver transplantation, those with an extension of the PVT to mesenteric vessels or with severe prothrombotic status. Key words: portal vein thrombosis, cirrhosis, anticoagulation.

HOMOCYSTEINE IS ASSOCIATED WITH FUTURE VENOUS THROMBOEMBOLISM IN TWO PROSPECTIVE COHORTS OF WOMEN

Numerous cross-sectional studies of venous thromboembolism (VTE) have identified plasma homocysteine as a potential risk factor for VTE. In contrast, prospective data are sparse with limited studies conducted among women. Given current interest in expanded indications for anticoagulation therapy, we

Combining oral anticoagulation and antiplatelet therapies: appropriate patient selection.

Anticoagulant therapy and antiplatelet therapy are used regularly for prevention of arterial and venous thrombosis, and combinations of the two drug classes are seen with relative frequency in clinical practice. While co-prescribing is as high as 39-55% in some real-world cohort studies, the number of patients that meet criteria for combination therapy based on the overall body of evidence is likely much lower. This may not always be realized by prescribers, and many patients may be continued on long term combination therapies that provide little additional benefit, and carry significant risk for harm. Given the heightened bleeding risk with combination therapies, prescribers should readily reassess the risk: benefit ratio in all patients on combination therapies. Combined antiplatelet and anticoagulant therapy should be used only in those with a low risk of bleeding who have a higher risk of thromboembolic disease events. Most patients with coronary artery disease, atrial fibrillation, peripheral arterial disease, or bioprosthetic cardiac valves will not benefit from combining antiplatelet and anticoagulant therapies. Conversely, patient populations more likely to derive benefit from antiplatelet-anticoagulant combinations include those with mechanical cardiac valves, patients undergoing percutaneous cardiac intervention who have another indication for anticoagulant therapy, and patients with recurrent thrombotic events while being treated with a single agent. This article will attempt to provide readers with a framework to assess which patient populations are likely to derive the greatest benefit with combination anticoagulant-antiplatelet therapies relative to the weighted risk for bleeding.

Дополнительные критерии стратификации риска ишемического инсульта у пациентов с фибрилляцией предсердий и одним не связанным с полом баллом по шкале CHA2DS2-VASс обусловленным артеиальной гипертонией

Purpose. Identification of characteristics, not included in the CHA2DS2-VASc scale, affecting the risk of ischemic stroke in patients with atrial fibrillation (AF) and one non-sex-related risk factor (RF), due to arterial hypertension (AH), of thromboembolic events on this scale. Methods. A “case-control” study was conducted according to retrospective analysis of medical records of patients with AF. The main group included hospitalized due to development of ischemic stroke patients with non-valvular AF and single additional to gender RF on the CHA2DS2-VASc scale due to AH in the period prior to the stroke development. As a comparison group, patients with comparable demographic characteristics, having non-valvular AF with single additional to gender RF on the CHA2DS2-VASc scale due to AH and no history of stroke or systemic embolism, were selected. Anamnesis data and the results of electrocardiography, echocardiography and ultrasonic duplex scanning of brachiocephalic arteries were analyzed. Results. The main group included 37 patients, age 60.15 (±6,21) years, 27% women. The control group included 88 patients, age 60.13 (±4,85) years, 37.58% women. Patients of the main group, compared to the control group patients, significantly more often showed permanent AF (48.7% and 14.3%, p = 0.01), signs of left ventricular hypertrophy (LVH) according to echocardiography (67.6% and 43.6% , p = 0.026), and thickening of the intima-media complex (cIMT) > 0.9 mm (73% and 25%, p <0.0001) according to ultrasonic duplex brachiocephalic arteries scanning. The univariate analysis showed a significant increase of ischemic stroke risk in the presence of a permanent AF (odds ratio (OR) 5.28; 95% confidence interval (CI) 1,15 - 6,94), LVH according to echocardiography (OR 2.81, 95% CI 1.15 - 6.91) and cIMT thickening (OR 7.88, 95% CI 2.96 - 20.94). Conclusion. When assessing the risk of ischemic stroke and making the decision on the oral anticoagulants appointment in patients with atrial fibrillation and single additional to gender risk factor on the CHA2DS2-VASc scale due to AH, in which the indications for anticoagulant therapy are not absolute, it is advisable to consider the data of echocardiography, ultrasonic duplex scanning of brachiocephalic arteries and the form of AF.

Is transesophageal echocardiography needed for evaluating tissue-based transient ischemic attack?

Transient ischemic attack (TIA) is a warning signal for stroke. A comprehensive evaluation of TIA may reduce the risk for subsequent stroke. Data on the findings of cardiac evaluation with transesophageal echocardiography (TEE) in patients with TIA are sparse. Our aims were to determine the frequency of TEE performance and to investigate the findings of TEE in patients with TIA based on the new definition of TIA (i.e., transient neurological symptoms without evidence of infarction). During a 4-year period (2011–2014), 1071 patients (mean age, 70 ± 13 years; female, 49.7%) with TIA were included in a prospective study and evaluated. Of 1071 consecutive patients suffering from TIA, 288 patients (27%) underwent TEE. The median time between admission and TEE was 6 days. Patients with TIA who were evaluated by TEE were younger (67 vs. 71 years, P < 0.001) than those who were not evaluated by TEE. They had a higher rate of sensibility disturbance as a TIA symptom (39% vs. 31%, P = 0.012) but a lower rate of previous stroke (15% vs. 25%, P = 0.001) and atrial fibrillation (2% vs. 21%, P < 0.001) than those who did not. Foramen ovale was detected in 71 patients (25.7%), atrial septal aneurysm in 13 patients (4.6%), and severe atherosclerotic plaques (grade 4 and 5) in the aortic arch in 25 patients (8.7%). One patient (0.3%) had a fibroma detected by TEE. In 17 of the 288 patients (6%) who underwent TEE, the indication for anticoagulation therapy was based on the TEE results, and 1 patient with fibroma underwent heart surgery. During hospitalization, 7 patients experienced a subsequent stroke, and 27 patients had a recurrent TIA. At 3 months following discharge, the rates of readmission, stroke, recurrent TIA, and death were 19%, 2.7%, 4.2%, and 1.6%, respectively. The rates of mortality (0.9% vs. 1.8%, P = 0.7), stroke risk (1.9% vs. 3.0%, P = 0.8), and recurrent TIA (5.0% vs. 3.9%, P = 0.8) were similar in patients who underwent TEE and in those who did not. Performing TEE in patients with tissue-based TIA is helpful in detecting cardiac sources for embolism and may indicate for anticoagulation.

Effectiveness and safety of oral anticoagulation with non-vitamin K antagonists compared to well-managed vitamin K antagonists in naïve patients with non-valvular atrial fibrillation: Propensity score matched cohort study

BackgroundThe global real-life impact of non-vitamin K antagonist oral anticoagulants (NOACs) introduction in the healthcare system in a setting of well-managed vitamin K antagonist (VKA) therapy has not been specifically addressed. MethodsWe did a population-based retrospective cohort study in naïve patients initiating oral anticoagulants for stroke prevention in atrial fibrillation in a region with a well-managed VKA therapy. NOAC and VKA cohorts were identified using Anatomical Therapeutic Chemical (ATC) codes, while excluding other indications for anticoagulation therapy using ICD-9CM codes. Propensity score was conducted using two different approaches: stratification and 1:1 matching. Event-rates were assessed using both an intention to treat (ITT) and as treated analyses. ResultsOf the 137,800 selected patients, 40,411 (6923 treated with NOACs and 33,488 with VKAs) were identified (June 2013–December 2015). Overall ischaemic stroke and major bleeding risk did not significantly differ between the groups both in the ITT and as treated analyses. Noteworthy, intracranial bleeding risk was lower with NOACs (stratified model HR=0.69; 95%CI 0.48–0.99; 1:1 matched model HR=0.73; 95%CI 0.47–1.13) reaching statistical significance in the as treated analysis in both stratified and 1:1 matched models (HR=0.51; 95%CI 0.32–0.80 and HR=0.52; 95%CI 0.30–0.90, respectively). ConclusionDespite well-managed anticoagulation with VKAs, NOACs' introduction has a positive global impact in the public healthcare system in terms of effectiveness and safety especially by lowering intracranial bleeding.

Warfarin Use and Increased Mortality in End-Stage Renal Disease

Background: Controversy exists regarding the benefits and risks of warfarin therapy in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. In this study, we assessed mortality and cardiovascular outcomes associated with warfarin treatment in patients with stages 3-5 CKD and ESRD admitted to the University of California-Irvine Medical Center. Methods: In a retrospective matched cohort study, we identified 59 adult patients with stages 3-6 CKD initiated on warfarin during the period 2011-2013, and 144 patients with stages 3-6 CKD who had indications for anticoagulation therapy but were not initiated on warfarin. All-cause mortality risk associated with warfarin treatment was estimated using Cox proportional hazard regression analysis, and the risk of significant bleeding and major adverse cardiovascular events were analyzed with Poisson regression analysis. Adjustment models were used to account for age, gender, diabetes mellitus, use of antiplatelet agents, and preexisting cardiovascular disease, and stratified by pre-dialysis CKD stages 3-5 vs. ESRD. Findings: During 5.8 years of follow-up, unadjusted mortality risk was higher in CKD patients on warfarin therapy (hazard ratio [HR] 2.34 with 95% CI 1.25-4.39; p < 0.01). After multivariate adjustment and stratification by CKD stage, the mortality risk remained significant in ESRD patients receiving warfarin (HR 6.62 with 95% CI 2.56-17.16; p < 0.001). Furthermore, adjusted rates of significant bleeding (incident rate ratio, IRR 3.57 with 95% CI 1.51-8.45; p < 0.01) and myocardial infarction (IRR 4.20 with 95% CI 1.78-9.91; p < 0.01) were higher among warfarin users. No differences in rates of ischemic or hemorrhagic strokes were found between the 2 groups. Conclusions: Warfarin use was associated with several-fold higher risk of death, bleeding, and myocardial infarction in dialysis patients. If additional studies suggest similar associations, the use of warfarin in dialysis patients warrants immediate reconsideration.

A review study to evaluate holmium:YAG laser lithotripsy with flexible ureteroscopy in patients on ongoing oral anticoagulant therapy.

The objective of this study was to evaluate the safety and efficacy of flexible ureteroscopy (FURS) and holmium:YAG laser lithotripsy for the treatment of upper urinary tract stones in patients on active oral anticoagulants. The records of 1081 patients who underwent flexible ureteroscopic holmium:YAG (Ho:YAG) laser lithotripsy for upper ureteral and renal calculi from 1999 to 2015 were retrospectively reviewed. A total of 84 patients on continuous oral anticoagulation or antiplatelet therapy (warfarin, aspirin, or clopidogrel) were identified. Of these patients, 40 were on warfarin, 25 on aspirin, 11 on clopidogrel, and 8 on both aspirin and clopidogrel. The drugs were not discontinued. The baseline characteristics, indications for anticoagulation therapy, perioperative data, stone-free rate, and complications were documented. Evaluation of outcomes was assessed at 1-, 3-, and 6-month follow-up postoperatively. Mean stone size was 19.7±9.4 (range 8 to 31mm). Twenty patients had upper ureteral and 64 patients had intrarenal calculi. Two patients had bilateral renal calculi. Mean operation time was 78.2±23.8min (range 17 to 144min). Two procedures (2.3%) in warfarin group were terminated due to persistent bleeding causing visual impairment. No transfusions were required. The mean serum hemoglobin levels did not change significantly (12.9±3.7 to 12.2±3.3g/dL). No thromboembolic or cardiac adverse events were observed perioperatively. The double-j (DJ) ureteral catheterization time was 29.6±9.3days (range 14 to 68days) and the hospital stay was 1.6±0.6days (range 1 to 4). The stone-free rate was 95.2% (80 patients) at 6months. Flexible ureteroscopic Ho:YAG laser lithotripsy in patients requiring long-term anticoagulation therapy seems to be a safe and effective procedure and should be considered as a first-line treatment option in such patients for the surgical management of upper urinary tract stones.

Characteristics of patients receiving district-nursing assistance for anticoagulant therapy: A descriptive cohort study

BackgroundChanges between health sectors and contact with multiple professionals are indisputable conditions for many frail elderly patients in anticoagulant therapy. This constitutes a risk factor. We aimed to describe the characteristics of patients receiving district-nursing assistance for their anticoagulant therapy in two Danish municipalities, with a specific focus on the complexity related to the number of professionals involved, number of hospital admissions, polypharmacy and co-morbidity. MethodWe performed a descriptive cohort study of patients receiving district-nursing assistance for their oral anticoagulant therapy. Data were retrieved from municipal patient records and validated by district nurses. ResultsThe cohort included 467 patients; 44.8% were men, 54.2% were women; their mean age was 81.1years. Four out of five lived in their own home, the remaining lived in nursing homes or comparable facilities. During the inclusion period, 46.7% had no hospital admissions, whereas 10.1% had three or more admissions. Besides anticoagulant therapy, 96,6% of the patients received more than three medications. We found an increased mean age among mentally impaired individuals with more than three additional medications and for whom the indications for anticoagulant therapy was stated as unknown, compared to the total sample. ConclusionDanish patients in anticoagulant therapy who receive district-nursing assistance related to the therapy are characterized by physical and mental frailty, polypharmacy, multiple readmissions, multiple sector shifts, and multiple health professionals involved in single patient pathways.

Anticoagulant Therapy In Ischemic Stroke Or TIA

Stroke is the leading cause of disability and the third leading cause of death . Anticoagulants have been used to treat patients with acute ischemic stroke for many years. Despite their widespread use, the usefulness of emergency anticoagulation is a subject of debate. Disagreements exist about the best agent to administer, the route of administration, the use of a bolus dose to start treatment, the level of anticoagulation required, and the duration of treatment. There are 2 types of anticoagulants: Parenteral and oral. Heparin is an anticoagulant that used parenteral. Oral anticoagulants are including Warfarin and new anticoagulants such as Dabigatrn,Rivaroxaban ,Apixaban and other newer drugs.In patients with noncardioembolic ischemic stroke or TIA antiplatelet agents are treatment of choice and preferred to anticoagulants.In cardioembolic ischemic stroke or TIA with high risk of reembolization anticoagulants are considered as preferred treatment. Warfarin, apixaban10mg/d ,Rivaroxaban20mg/d, and dabigatran 150 mg/d are all indicated for the prevention of recurrent stroke in patients with nonvalvular AF, whether paroxysmal or permanent.Also anticoagulant therapy is recommended for ischemic stroke or TIA patients in the setting of acute MI, atrial or ventricular thrombosis or dilated and restricted cardiomyopathy. Some valvular heart diseases are other indication for anticoagulant therapy in ischemic stroke or TIA patients.Ischemic Stroke or TIA in patients with Cerebral vein thrombosis and known hypercoagulable state specially anti phospholipid antibody syndrome are other indications for anticoagulant treatment.

HOW TO REDUCE GASTROINTESTINAL BLEEDING RISK ON ANTICOAGULATION THERAPY IN NON-VALVULAR ATRIAL FIBRILLATION?

Atrial fibrillation (AF) is a significant risk factor for stroke and systemic embolism. For prevention of these complications, most AF patients are indicated to take anticoagulants, that reduce the risk cardioembolic strokes, but increase the risk of bleedings, and the most prevalent are gastrointestinal (GIB). Aim. To assess the rate of pathological changes in esophagus, stomach and duodenum, predisposing for GID, in AF patient with higher risk of stroke and absolute indications for anticoagulation therapy. Material and methods. The analysis done, of case histories of hospitalized patients in the therapeutical university clinics, in the year 2016; of those — 263 with non-valvular AF. Among 222 patients with AF and higher risk of stroke, who had indications for anticoagulants, 103 underwent screening fibroesophagogastroduodenoscopy (FEGDS). Results. The FEGDS, performed in 103 patients with non-valvular AF and high risk of stroke, in 45,6% revealed diseases predisposing to GIB, including esophageal cancer — 1 (2,1%), gastric ulcer — 4 (8,5%), duodenal ulcer — 2 (4,3%), erosive esophagitis and reflux disease — 5 (10,6%), varicose veins of esophagus — 4 (8,5%), erosive gastritis — 31 (66,0%) and erosive duodenitis — 3 (6,4%). Combination of diseases was found in 10 (21,3%) patients. Conclusion. Patients with non-valvular AF and high stroke risk, before starting therapy with anticoagulants, it is aimworthy to perform FEGDS for on-time screening for esophageal, gastric, duodenal pathologies predisposing to GIB.

Assessment of the mean time in the therapeutic INR range and the SAME-TT2R2 score in patients with atrial fibrillation and cognitive impairment.

INTRODUCTION Most patients with atrial fibrillation (AF) are elderly and may have an increased risk of cognitive disorders. Low mean values of the therapeutic international normalized ratio (INR) range (TTR) (≤60%) are associated with increased risk of stroke, vascular events, and bleeding complications. OBJECTIVES The aim of the study was to evaluate the efficacy of long-term anticoagulant therapy in patients treated with vitamin K antagonists (VKAs), depending on their cognitive functions. In addition, we used the SAMe-TT2R2 risk score to predict the risk of ineffective anticoagulation. PATIENTS AND METHODS The analysis comprised 154 patients (68 men and 86 women; mean age, 76 ±10 years) with AF and indications for long-term therapy with VKA (CHA2DS2-VASc score ≥1, HAS-BLED score <3). Cognitive functions were evaluated using the Mini-Mental State Examination (MMSE) score. The efficacy of VKA therapy was determined by the TTR values from the preceding 6 months of treatment. We used the SAMe-TT2R2 score to identify patients who were likely to have poor INR control. RESULTS Depending on the number of MMSE points, patients treated with VKAs were divided into 2 groups: patients with normal cognitive functions (MMSE score ≥27; n = 62) and those with cognitive impairment (MMSE score <27; n = 42). Despite the fact that all patients had indications for anticoagulant therapy, 50 patients (32%) received no VKAs on admission. The mean TTR value exceeded 60% in 61% of patients with an MMSE score of 27 points or higher, whereas mean TTR value was 28% in patients with an MMSE score of less than 27 (P <0.0001). Patients with a SAMe-TT2R2 score of 0 to 1 had higher TTR values than those with a SAMe-TT2R2 score of 2 or higher (r = -0.24; P <0.05 ). The cognitive status was significantly more impaired in patients with persistent and permanent AF compared with patients with paroxysmal AF (MMSE score, 25.8 ±3.7 vs 28.6 ±2; P <0.0001). CONCLUSIONS Cognitive disorders in patients with AF significantly reduce the efficacy of VKA therapy. The decision to administer VKA treatment should be based not only on the CHA2DS2-VASc and HAS-BLED scores, but also on the SAMe-TT2R2 score and the evaluation of the patient's cognitive functions.

P44 Anticoagulation control in adults with congenital heart disease

Background Among patients with acquired cardiovascular disease taking oral vitamin K antagonist medications, time within therapeutic range (TTR) is considered poor when below 60%. To date, however, there are no data about anticoagulation control in adults with congenital heart disease (CHD). This is concerning given that they represent an emerging and growing population of cardiac patients with specific management considerations. Objectives In a sample of adults with CHD taking oral vitamin K antagonist medications, we investigated (i) TTR and (ii) socio-demographic and medical factors associated with lower anticoagulation control. Methods In this retrospective study, the following were study inclusion criteria: age ≥ 18 years, diagnosis of CHD, prescribed oral vitamin K antagonist medication, followed in the thrombosis clinic at least once between January 2005 and December 2010, and adequate frequency of recording of INR values. We documented medical and socio-demographic background, indication for anticoagulation therapy, international normalised ratio (INR) values, and TTR; data were recorded through December 2013. Results We identified 119 eligible patients (49% male; mean age = 39 ± 17 years; mean follow up duration = 4 ± 2.3 years). Defect complexity was categorised as simple (n = 29; 24%), moderate (n = 46, 39%) or great (n = 44; 37%). Specific indications for oral anticoagulation were cardiac arrhythmias (n = 60; 51%), prior thrombus/emboli event (n = 30; 25%), mechanical valves (n = 24; 20%), and other (n = 5; 4%). Twenty-three patients (19%) had a documented psychiatric disorder and 21 patients (18%) had a history of medication non-adherence. Of 71 patients with known educational attainment, 45 (38%) had earned college or university degrees. Of 119 study patients, the mean TTR was 49 ± 19% (range: 0–89%); 82 patients (69%) had poor anticoagulation control (TTR Conclusions Among our study cohort of adults with CHD, patients were within therapeutic INR range only half of the time and more than two-thirds of patients had poor anticoagulation control. Poorer anticoagulation control was observed in patients with moderate defect complexity, with mechanical valves, and with a documented history of medication non-adherence. Future investigation into the clinical outcomes of sub-optimal INR control as well as the potential role of novel oral anticoagulant agents is encouraged.

Utilization of Dabigatran for Atrial Fibrillation at 3 Tertiary Care Centres.

The outpatient management of stroke prevention for patients with atrial fibrillation has recently been published and provides insight into the benefits and risks of the new direct-acting oral anti-coagulants. However, real-world use of these agents for hospital inpatients requires additional study. To determine prescribing patterns for dabigatran at 3 Canadian hospitals, specifically adherence with the hospitals' prescribing restriction limiting dabigatran to patients with nonvalvular atrial fibrillation and creatinine clearance above 30 mL/min (primary outcome) and assessment of age-related prescribing, prescribing of medications with defined contraindications or potential for interaction when given concurrently with dabigatran, and use of risk stratification tools (secondary outcomes). A retrospective chart review of patients for whom dabigatran was prescribed from August to October 2011 was performed at 3 hospitals in Toronto, Ontario. Descriptive statistics were used for all outcomes assessed. Overall, dabigatran was prescribed for 69 inpatients, of whom 16 (23%) were new users (dabigatran initiated during hospital admission) and 53 (77%) were prior users (dabigatran prescribed before admission to hospital). Fifty-eight patients (84%; 14 new users and 44 prior users) received dabigatran according to the hospitals' prescribing restriction. For the remaining 11 patients, dabigatran therapy did not meet prescribing restrictions for use because of valvular disease or presence of prosthetic valve (10 patients [14% of the total sample]) and impaired renal function (1 patient [1%]). Among those whose dabigatran therapy met the prescribing restrictions for use, amiodarone and acetylsalicylic acid were the most common concurrently prescribed medications (17 patients [29%] and 14 patients [24%], respectively). Stroke and bleeding risk were documented for only 27 patients (47%) and 10 patients (17%), respectively. At the study hospitals, dabigatran was appropriately prescribed for the indication of nonvalvular atrial fibrillation in patients without renal impairment in most cases. However, greater consideration of cardiac history (including valvular disease and presence of prosthetic valves), drug interactions, and documentation of risks and benefits is warranted. These research findings highlight the importance of and opportunity for pharmacist review and involvement in assessment and selection of patients with indications for anticoagulant therapy, particularly when agents are new to the market.

Influence of CYP2C9 polymorphism on the fall in International Normalized Ratio in patients interrupting warfarin therapy before elective surgery

Patients on warfarin are normally required to stop treatment for a fixed number of days prior to an invasive procedure. However, the anticoagulant activity of warfarin subsides at different rates among different patients. The aim of this study was to investigate the potential influence of CYP2C9 polymorphism on the variable rate of fall in the International Normalized Ratio (INR) in patients withdrawing from warfarin treatment prior to elective surgery. One hundred and fifty-two patients aged 43-93years were recruited. Demographic data on age, height, weight, gender, daily warfarin dose, indication for anticoagulation therapy, medical diagnosis, surgical operation planned and concomitant medication were recorded. A blood sample was taken for later CYP2C9 genotyping. For patients with two CYP2C9 variant alleles (CYP2C9*2*2 or CYP2C9*2*3), the odds of having an INR of ≥1.5 before the planned day of surgery were 8.64 times greater (95% confidence interval [CI]2.25-33.25) than for other patients. Multiple regression analysis revealed that the rate of fall in the INR was reduced in the presence of two CYP2C9 variant alleles, as well as increasing patient age, weight and number of comorbidities, and increased with increasing initial INR (F5,132 =242.9, P<0.0001), all of which accounted for ~90% of the interindividual variability in the fall in INR. A genotype-guided protocol to tailor warfarin withdrawal according to an individual patient's CYP2C9 genotype could reduce cancellation or delays of planned procedures, and could also be beneficial when transitioning patients from warfarin to one of the new oral anticoagulants.

Post-PCI Antithrombotic Therapy in Patients Requiring Long-Term Anticoagulation.

The number of patients who undergo percutaneous coronary intervention (PCI) and additionally require chronic anticoagulation for a variety of indications is not insignificant. The choice of antithrombotic therapy after PCI in patients with chronic indications for anticoagulation therapy remains a challenge for interventional cardiologists, as the risk of bleeding must be adequately weighed against the benefit of preventing future ischemic events. While these clinical scenarios are encountered in approximately 10 % of patients undergoing PCI, current practice guidelines do not sufficiently guide physicians as to how to best treat these PCI patients requiring chronic anticoagulation. Notwithstanding the clinical difficulties of treating such patients, there are several recent studies and analyses that have assessed optimal antithrombotic strategies in the PCI population, and there are several others that are currently underway. This review evaluates the currently available data and clinical scenarios commonly encountered by treating physicians.

Anticoagulant therapy for venous thromboembolism detected by Doppler ultrasound in patients with metastatic colorectal cancer receiving bevacizumab.

BackgroundDoppler ultrasound imaging is useful for management of venous thromboembolism associated with a subclavicular implantable central venous access system in patients receiving bevacizumab (Bev). We investigated the efficacy and safety of our anticoagulant regimen based on Doppler findings.MethodsPatients aged ≤75 years with metastatic colorectal cancer, no history of thromboembolism, and no prior use of Bev received chemotherapy plus Bev. Doppler ultrasound imaging of the deep venous system to detect thrombosis was performed after the first course of Bev and repeated after the third course in patients with asymptomatic thrombosis. Indications for anticoagulant therapy in patients with asymptomatic thrombosis were as follows: enlarging thrombus (E), thrombus >40 mm in diameter (S), thrombus involving the superior vena cava (C), and decreased blood flow (V).ResultsAmong 79 patients enrolled in this study, asymptomatic thrombosis was detected in 56 patients (70.9%) by Doppler ultrasound imaging after the first course of Bev and there was no thrombus in 23 patients (29.1%). Of these 56 patients, 11 (19.6%) received anticoagulant therapy with warfarin, including eight after the first course and three after follow-up imaging. S + V was observed in four of 11 patients (36.4%), as well as V in two (18.2%), S + V + C in one (9.1%), E + S + V in one (9.1%), E + C in one (9.1%), E in one (9.1%), and C in one (9.1%). All patients resumed chemotherapy, including seven who resumed Bev. Improvement or stabilization of thrombi was achieved in ten patients (90.9%). Only one patient had symptomatic thromboembolism. Mild bleeding due to anticoagulant therapy occurred in six patients (54.5%), but there were no treatment-related severe adverse events or deaths. Severe thromboembolism was not observed in the other 68 patients.ConclusionOur anticoagulant protocol for asymptomatic thrombosis detected by Doppler ultrasound imaging was effective at preventing severe thromboembolism during continued treatment with Bev.