warfarin and Diabetes-Mellitus

This study incorporates the results of subgroup analyses of currently published randomized controlled trials (RCTs) and real-world cohort studies to compare the effectiveness and safety of new direct oral anticoagulants (NOACs) and warfarin among nonvalvular atrial fibrillation patients with diabetes.. The PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov databases were searched. Five retrospective cohort studies and four subgroup analyses of RCTs were included in this meta-analysis.. A meta-analysis of the data of 26,7272 patients showed that for patients with nonvalvular atrial fibrillation and diabetes, NOACs can significantly reduce the incidence of stroke/systemic embolism (SSE), ischaemic stroke, and haemorrhagic stroke compared with warfarin, with no significant difference in major bleeding and all-cause mortality. Additionally, NOACs were superior to warfarin in the incidence of intracranial bleeding, gastrointestinal bleeding, myocardial infarction, and vascular death.. Among nonvalvular atrial fibrillation patients with diabetes, NOACs were associated with a lower risk of SSE versus warfarin, with no significant difference in major bleeding. Therefore, NOACs may be a better clinical choice.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome; Warfarin

This meta-analysis was conducted to compare the efficacy and safety of rivaroxaban with warfarin in patients with atrial fibrillation (AF) and diabetes mellitus.. PubMed, Embase, Cochrane Library, and Web of Science databases were systematically searched from the establishment of databases up to 15 October 2019. Studies on efficacy and safety outcomes of rivaroxaban and warfarin were included. Efficacy and safety outcomes, including stroke, ischemic stroke, stroke or systemic embolism, myocardial infarction, major adverse cardiac events, major bleeding, intracranial hemorrhage, and major gastrointestinal bleeding were collected for meta-analysis.. Compared with warfarin, rivaroxaban could significantly reduce stroke (risk ratio [RR] 0.77; 95% confidence interval [CI] 0.63-0.95; P = 0.01), ischemic stroke (RR 0.74; 95% CI 0.63-0.87; P = 0.0004), stroke or systemic embolism (RR 0.73; 95% CI 0.60-0.89; P = 0.002), myocardial infarction (RR 0.68; 95% CI 0.56-0.82; P < 0.0001), and major adverse cardiac events (RR 0.71; 95% CI 0.53-0.94; P = 0.02) in patients with AF and diabetes. Moreover, rivaroxaban was associated with a lower risk of major bleeding (RR 0.79; 95% CI 0.65-0.96; P = 0.02), intracranial hemorrhage (RR 0.52; 95% CI 0.39-0.69; P < 0.00001), and major gastrointestinal bleeding (RR 0.74; 95% CI 0.56-0.98; P = 0.04). Similar results were obtained in stratified meta-analysis of cohort studies.. Our study suggests a favorable risk-benefit profile of rivaroxaban, with superior efficacy and safety over warfarin in patients with AF and diabetes.

Topics: Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Diabetes Mellitus; Hemorrhage; Humans; Myocardial Infarction; Rivaroxaban; Stroke; Warfarin

With the aim of recommending proper anticoagulation for patients with atrial fibrillation (AF) and diabetes mellitus, we performed the network meta-analysis comparing the non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in terms of efficacy (stroke or systemic embolism) and safety (major bleeding) outcome.. A systematic search of PubMed, EMBASE, Web of Science and Cochrane Library was performed with the items "dabigatran, edoxaban, apixaban, rivaroxaban, warfarin, AF and diabetes mellitus". On the basis of R (version 3.5.1, R Foundation for Statistical Computing) and JAGS (version 4.3.0) to perform the network meta-analysis, our work was also conducted with the help of NetMetaXL (version1.6.1) and winBUGS (version1.4.3) to obtain the cumulative ranking curve (SUCRA) of treatments.. With respect to the most effective drug for preventing systemic embolism or stroke, there was a high probability that dabigatran150 (SUCRA 0.88) would ranked first, followed by apixaban (SUCRA 0.63), dabigatran110 (SUCRA 0.59) and rivaroxaban (SUCRA 0.51). In comparison, probability of ranking the safest drug for preventing major bleeding was edoxaban (SUCRA 0.94), followed by dabigatran110 (SUCRA 0.59) and rivaroxaban (SUCRA 0.52).. In patients suffering from AF and diabetes, dabigatran 110 mg (bid) was more likely to become the choice for its performance on preventing systemic embolism or stroke and major bleeding, followed by rivaroxaban 20 mg (QD).

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Humans; Network Meta-Analysis; Stroke; Warfarin

Atrial fibrillation is one of the most common concomitant diseases in patients with diabetes mellitus (DM). Meta-analyses of multiple studies have shown that the risk of AF is higher for diabetic patients with impaired glucose homeostasis than for patients without DM. Patients with AF and DM were younger, more frequently had arterial hypertension, chronic kidney disease, heart failure, and ischemic heart disease, and stroke and were characterized with a more severe course of AF. The article discusses possible mechanisms of the mutually aggravating effects of DM and AF, scales for evaluating the risk of bleeding (CHADS2, CHA2DS2‑VASc, HAS-BLED), and the role of anticoagulants. A meta-analysis of 16 randomized clinical studies, including 9 874 patients, has demonstrated the efficacy of oral anticoagulants in prevention of stroke with an overall decrease in the relative risk by 62 % compared to placebo (95% confidence interval, from 48 to 72 ). For prevention of complications in patients with AF and DM, current antithrombotic therapies can be used, specifically the oral factor Xa inhibitor, rivaroxaban, which is the best studied in patients with AF and DM and represents a possible alternative to warfarin in such patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Humans; Risk Factors; Rivaroxaban; Stroke; Warfarin

Direct oral anticoagulants (DOACs) include dabigatran, which inhibits thrombin, and apixaban, edoxaban, and rivaroxaban, which inhibit factor Xa. They have been extensively studied in large trials involving patients affected by the most common cardiovascular diseases. As the presence of diabetes leads to peculiar changes in primary and secondary hemostasis, in this review we highlight the current evidence regarding DOAC use in diabetic patients included in the majority of recently conducted studies. Overall, in trials involving patients with atrial fibrillation, data seem to confirm at least a similar efficacy and safety of DOACs compared to warfarin in patients with or without diabetes. Furthermore, in diabetic patients, treatment with DOACs is associated with a significant relative reduction in vascular death compared to warfarin. In trials enrolling patients undergoing percutaneous coronary intervention, results concerning bleeding events are consistent in patients with or without diabetes. With regards to the COMPASS study, in patients with diabetes (n = 10,241), addition of rivaroxaban 2.5 mg to aspirin resulted in a significantly lower incidence of major adverse cardiovascular events (HR 0.74, 95% CI 0.61-0.90; interaction p = 0.68) with higher rates of major bleeding expected (HR 1.70, 95% CI 1.25-2.31). The 3287 patients with peripheral artery disease and diabetes receiving rivaroxaban plus aspirin had a twofold higher absolute reduction in the composite endpoint (cardiovascular death, myocardial infarction, and stroke) than patients without diabetes. Finally, we report the involvement of cytochromes or P-glycoprotein on the metabolism of the most commonly prescribed glucose-lowering drugs. No clinically relevant interactions are expected during the concomitant use of DOACs and anti-diabetic agents.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Diabetic Angiopathies; Fibrinolytic Agents; Hemorrhage; Humans; Myocardial Infarction; Stroke; Treatment Outcome; Warfarin

In patients with atrial fibrillation (AF), the safety and efficacy of nonvitamin K antagonist oral anticoagulants (NOACs) vs warfarin according to diabetes mellitus (DM) status are not completely characterized. We performed a meta-analysis to clarify whether in these patients the strategy of oral anticoagulation should be tailored to diabetes status. In this study-level meta-analysis, we included 4 randomized phase III trials comparing NOACs and warfarin in patients with nonvalvular AF; a total of 18 134 patients with DM and 40 454 without DM were overall considered. Incidence of the following outcome measures was evaluated during the follow-up: stroke or systemic embolism, ischemic stroke, major bleeding, intracranial bleeding, and vascular death. Use of NOACs compared with warfarin reduced stroke/systemic embolism in diabetic (Risk Ratios [RR] 0.80, 95% CI 0.68-0.93; P = .004) and nondiabetic patients (RR 0.83, 0.73-0.93; P = .001) (P for interaction .72). No interaction between diabetes status and benefits of NOACs was found for the occurrence of ischemic stroke, major bleeding, or intracranial bleeding (P for interaction >.05 for each comparison). Reduction of vascular death rates with NOACs was significant in diabetic patients (4.97% vs 5.99% with warfarin; RR 0.83, 0.72-0.96; P = .01), in whom absolute the reduction of this outcome measure was higher than in nondiabetics (1.02% vs 0.27%), although no interaction was present (P = .23). Results of this meta-analysis support the safety and efficacy of NOACs compared with warfarin in diabetic patients with nonvalvular AF.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Diabetes Complications; Diabetes Mellitus; Humans; Prognosis; Randomized Controlled Trials as Topic; Safety; Stroke; Vitamin K; Warfarin

Recent studies have indicated that osteocalcin, a peptide secreted by osteoblasts, functions as an anti-diabetogenic hormone in mice. Osteocalcin knock out mice exhibit obesity, hyperglycemia, and decreased insulin secretion relative to wild-type mice. Treatment with non-carboxylated osteocalcin upregulates energy expenditure, and ameliorates obesity and diabetes in mouse models of obesity-related diabetes. Of interest, the beneficial effects of osteocalcin were shown to be specific to non-carboxylated osteocalcin. This appears, however, inconsistent with recent clinical studies showing insulin-sensitizing effects of vitamin K, which promotes gamma-carboxylation of osteocalcin. These findings shed new light on the crosstalk between bone and energy expenditure, and lead to new questions. These questions include: (1) Does non-carboxylated osteocalcin exert the beneficial effects in humans?; (2) Does warfarin, a vitamin K antagonist, improve insulin, sensitivity and lower blood glucose levels?; (3) and Do estrogen and bisphosphonate, which reduce circulating osteocalcin, contribute to insulin resistance and obesity? These issues await further investigations.

Topics: Animals; Bone Density Conservation Agents; Diabetes Mellitus; Diphosphonates; Estrogens; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Resistance; Mice; Obesity; Osteoblasts; Osteocalcin; Vitamin K; Warfarin

To elucidate predisposing factors for enlargement of intracerebral hematoma (ICH) during warfarin therapy, we reviewed 47 patients on warfarin who developed acute ICH and determined relationships among ICH enlargement, INR reversal and clinical data. Among 36 patients treated to counteract the effects of warfarin within 24 h of onset, ICH increased in 10 patients (enlarged group), but remained unchanged in the remaining 26 (unchanged group), while ICH remained unchanged in another 11 patients in whom the effect of warfarin was reversed after 24 h. The international normalized ratio (INR) was counteracted immediately in 11 patients treated with prothrombin complex concentrate (PCC) but gradually in the other 36 treated by reducing the dose of warfarin, or by administering vitamin K or fresh frozen plasma. Multivariate analysis with a logistic regression model showed an INR value <2.0 at admission or for 24 h after immediate INR correction with PCC prevented ICH enlargement (OR 0.069, 95%CI 0.006-0.789, p = 0.031). An INR value of >2.0 within 24 h of ICH seems an important predisposing factor for ICH enlargement.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Cerebral Hemorrhage; Comorbidity; Diabetes Mellitus; Disease Progression; Female; Humans; Hypercholesterolemia; Hypertension; International Normalized Ratio; Liver Diseases; Male; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Retrospective Studies; Risk Factors; Tomography, X-Ray Computed; Vitamin K; Warfarin

To conduct a systematic review of drug induced adverse ocular effects in diabetes to determine if this approach identified any previously unrecognised adverse drug effects; to make a preliminary assessment of the feasibility of this approach in identifying adverse drug reactions; and to assess the current accessibility of this information to prescribing physicians.. Literature search of online biomedical databases. The search strategy linked eye disorders with adverse drug reactions and diabetes. Source journals were classified as medical, pharmaceutical, diabetes related, or ophthalmological. It was determined whether the reactions identified were recorded in drug datasheets and the British National Formulary.. 63 references fulfilled the selection criteria, of which 45 were considered to be relevant to the study. The majority of these were case reports but cross sectional surveys, case-control and cohort studies, and review articles were also identified. 61% of the reactions were not recorded in the British National Formulary and 41% were not recorded in the datasheets. 55% appeared in specialist ophthalmology journals.. This is a feasible approach to the identification of adverse drug reactions. Adverse reactions not listed in the most commonly used reference sources were found. The majority were published in specialist ophthalmology journals which might not be seen by prescribing physicians.

Topics: Chlorpropamide; Contraceptives, Oral; Diabetes Mellitus; Eye Diseases; Glucocorticoids; Humans; Interferons; Online Systems; Streptokinase; Warfarin

Several recent randomized clinical trials of anticoagulation in atrial fibrillation have demonstrated significant reduction in stroke rates with a small incidence of bleeding complications. The objective of this study was to determine whether the recommendations resulting from these trials have been implemented into routine practice, and if the anticoagulation control, therapeutic efficacy, and low complication rates achieved in the trials have been matched in community practice.. We analyzed the anticoagulation practices and outcomes obtained for patients in atrial fibrillation at a large staff model health maintenance organization (HMO). We reviewed the medical records of all patients in atrial fibrillation as of April 1990. We compared demographic characteristics and clinical risk factors between HMO patients and those in the clinical trials. We also compared anticoagulation monitoring, adequacy of anticoagulation control, and clinical outcomes at the HMO with those achieved in the clinical trials.. Of 238 HMO patients in atrial fibrillation, 198 were without contraindications and therefore eligible for anticoagulation. Of these, 168 were offered anticoagulation (84.8%) and 156 were receiving anticoagulation therapy (78.8% of those eligible). The HMO patients had a greater prevalence of comorbidities than those in the clinical trials. The routine monitoring interval at the HMO was estimated at between 36.3 and 40.9 days (compared with 21 to 28 days reported in the clinical trials). The prothrombin time ratios at the HMO were in the target range on 50% of days compared with 68% of days in the clinical trials. The annual stroke and major bleeding rates in the HMO patients (1.3% and 0.6%, respectively) were not significantly different from the rates in the clinical trials (1.3% and 1.1%, respectively). The annual minor bleeding rate of 13.6% at the HMO was greater than the 7.8% to 8.4% rates in the two trials with better anticoagulation control (Boston Area Anticoagulation Trial for Atrial Fibrillation and Stroke Prevention in Atrial Fibrillation Study) but was not significantly different than the rates of 12.7% and 13.7% of the two trials with poorer anticoagulation control (Canadian Atrial Fibrillation Anticoagulation Study and Stroke Prevention in Nonrheumatic Atrial Fibrillation Study).. Anticoagulation practices in this community setting appear to be good in that a large majority of patients were receiving anticoagulation therapy, and there were few major adverse outcomes. However, this study illustrates two common problems in attempting to apply the results of randomized clinical trials to routine practice: (1) differences between community patient populations and those on which the conclusions of clinical trials are based, and (2) less successful application of therapeutic interventions in settings other than that of a controlled clinical trial. The greater prevalence of comorbidities in the HMO patient population appears to convey a greater overall risk of thromboembolism and bleeding complications than in the clinical trials. In addition, the suboptimal anticoagulation control achieved at the HMO may increase the risks and decrease the potential benefits compared with those achieved in the clinical trials. Thus, the efficacy demonstrated in the clinical trials of anticoagulation in atrial fibrillation may not be directly translated into effectiveness in practice.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Contraindications; Diabetes Mellitus; Female; Health Maintenance Organizations; Humans; Hypertension; Male; Practice Patterns, Physicians'; Prothrombin Time; Randomized Controlled Trials as Topic; Risk; Treatment Outcome; Warfarin

The RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial demonstrated that higher-risk patients with atrial fibrillation had lower rates of stroke or systemic embolism and a similar rate of major bleeding, on average, when treated with dabigatran 150mg compared to warfarin. Since population-level averages may not apply to individual patients, estimating the heterogeneity of treatment effect can improve application of RE-LY in clinical practice.. For 18040 patients randomized in RE-LY, we used patient-level data to develop multivariable models to predict the risk for stroke or systemic embolism and for major bleeding including all three treatment groups (dabigatran 110mg, dabigatran 150mg, and warfarin) over a median follow up of 2.0 years. The mean predicted absolute risk reduction (ARR) for stroke/systemic embolism with dabigatran 150mg compared to warfarin was 1.32% (range 11.6% lower to 3.30% higher risk). The mean predicted ARR for bleeding was 0.41% (range 8.93% lower to 63.4% higher risk). Patients with increased stroke/systemic embolism risk included those with prior stroke/TIA (OR 2.01), diabetics on warfarin (OR 2.00), and older patients on dabigatran 150mg (OR 1.68 for every 10-year increase). Major bleeding risk was higher in patients on aspirin (OR 1.25), with a history of diabetes (OR 1.34) or prior stroke/TIA (OR 1.22), those with heart failure on dabigatran 110mg (OR 1.52), older patients on either dabigatran 110mg or 150mg (OR 1.57 and 1.93, respectively, for each 10-year increase), and heavier patients on dabigatran 110mg or 150mg; patients in a region outside the United States and Canada and with better renal function had lower bleeding risk.. There is substantial heterogeneity in the benefits and risks of dabigatran relative to warfarin among patients with atrial fibrillation. Using individualized estimates may enable shared decision making and facilitate more appropriate use of dabigatran; as such, it should be prospectively tested.. www.clinicaltrials.gov number, NCT00262600.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Canada; Dabigatran; Diabetes Mellitus; Female; Hemorrhage; Humans; Male; Middle Aged; Risk Assessment; Risk Factors; Stroke; Time Factors; Warfarin

Vascular calcification is common in diabetic patients. Warfarin has been associated with renovascular calcification and worsening renal function; rivaroxaban may provide renopreservation by decreasing vascular inflammation. We compared the impact of rivaroxaban and warfarin on renal outcomes in diabetic patients with non-valvular atrial fibrillation (NVAF).. Using United States IBM MarketScan data from January 2011 to December 2017, we identified adults with both NVAF and diabetes, newly-initiated on rivaroxaban or warfarin with ≥12-month insurance coverage prior to anticoagulation initiation. Patients with Stage 5 chronic kidney disease (CKD) or undergoing haemodialysis at baseline were excluded. Differences in baseline covariates between cohorts were adjusted using inverse probability-of-treatment weighting (IPTW) based on propensity scores (absolute standardized differences <0.1 achieved for all after adjustment). Outcomes included incidence rates of emergency department/hospital admissions for acute kidney injury (AKI) and the composite of the development of Stage 5 CKD or need for haemodialysis. Patients were followed until an event, index anticoagulant discontinuation/switch, insurance disenrollment, or end-of-data availability. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression. We assessed 10 017 rivaroxaban (22.6% received a reduced dose) and 11 665 warfarin users. In comparison to warfarin, rivaroxaban was associated with lower risks of AKI (HR = 0.83, 95% CI = 0.74-0.92) and development of Stage 5 CKD or need for haemodialysis (HR = 0.82, 95% CI = 0.70-0.96). Sensitivity and subgroup analyses had similar effects as the base-case analysis.. Rivaroxaban appears to be associated with lower risks of undesirable renal outcomes vs. warfarin in diabetic NVAF patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Factor Xa Inhibitors; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Incidence; Male; Middle Aged; Propensity Score; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; United States; Warfarin; Young Adult

The aim of this study was to evaluate dabigatran dual therapy versus warfarin triple therapy in patients with or without diabetes mellitus in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial.. It is unclear whether dual therapy is as safe and efficacious as triple therapy in patients with atrial fibrillation with diabetes following percutaneous coronary intervention.. In RE-DUAL PCI, 2,725 patients with atrial fibrillation (993 with diabetes) who had undergone PCI were assigned to warfarin triple therapy (warfarin, clopidogrel or ticagrelor, and aspirin) or dabigatran dual therapy (dabigatran 110 mg or 150 mg twice daily and clopidogrel or ticagrelor). Median follow-up was 13 months. The primary outcome was the composite of major bleeding or clinically relevant nonmajor bleeding, and the main efficacy outcome was the composite of death, thromboembolic events, or unplanned revascularization.. Among patients with diabetes, the incidence of major bleeding or clinically relevant nonmajor bleeding was 15.2% in the dabigatran 110 mg dual therapy group versus 27.5% in the warfarin triple therapy group (hazard ratio [HR]: 0.48; 95% confidence interval [CI] 0.35 to 0.67) and 23.8% in the dabigatran 150 mg dual therapy group versus 25.1% in the warfarin triple therapy group (HR: 0.87; 95% CI: 0.62 to 1.22). Risk for major bleeding or clinically relevant nonmajor bleeding was also reduced with both dabigatran doses among patients without diabetes (dabigatran 110 mg dual therapy: HR: 0.54; 95% CI: 0.42 to 0.70; dabigatran 150 mg dual therapy: HR: 0.63; 95% CI: 0.48 to 0.83). Risk for the efficacy endpoint was comparable between treatment groups for both patients with and those without diabetes. No interaction between treatment and diabetes subgroup could be observed, either for bleeding or for composite efficacy endpoints.. In this subgroup analysis, dabigatran dual therapy had a lower risk for bleeding and a comparable rate of the efficacy endpoint compared with warfarin triple therapy in patients with atrial fibrillation with or without diabetes following percutaneous coronary intervention.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Diabetes Mellitus; Drug Substitution; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome; Warfarin

Statins have been shown to decrease stroke risk in patients with cardiovascular risk factors but not to prevent recurrence of ischemic stroke in patients with atrial fibrillation (AF). The present subanalysis aimed to clarify the efficacy of combined use of warfarin and statins in patients with nonvalvular AF (NVAF) with coronary artery disease, diabetes mellitus (DM), or hypertension. The effects of adding statins to warfarin were compared with those of warfarin alone in patients with NVAF with the data set of J-RHYTHM Registry, a prospective, observational study with a 2-year follow-up. End points included thromboembolism, major hemorrhage, all-cause mortality, and cardiovascular mortality. Of 7,406 patients with NVAF and follow-up data, 6,404 patients received warfarin at baseline. Of these, 1,605 patients also received a statin. Patients in the warfarin plus statin group showed significantly lower all-cause mortality compared with those on warfarin alone (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.38 to 0.87, p = 0.0089), although thromboembolic event rates did not differ significantly (HR 0.73, 95% CI 0.44 to 1.20, p = 0.21). In contrast, in 1,223 patients with DM, the warfarin plus statin group showed significantly lower thromboembolic event rates than the warfarin-alone group (HR 0.33, 95% CI 0.11 to 0.96, p = 0.041). Interestingly, in patients with coronary artery disease or with hypertension, the addition of statin to warfarin did not decrease the frequency of thromboembolic events. In conclusion, in Japanese patients with NVAF with DM, a combination of warfarin and a statin could be clinically beneficial for preventing thromboembolic events.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cause of Death; Diabetes Mellitus; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Japan; Male; Middle Aged; Prognosis; Prospective Studies; Registries; Risk Factors; Survival Rate; Thromboembolism; Time Factors; Warfarin

Diabetes mellitus (DM) is frequent among patients with atrial fibrillation (AF). The RE-LY trial permits evaluation of patient characteristics, outcomes and the effectiveness of dabigatran etexilate among diabetic individuals.. Patient characteristics and outcomes were compared between diabetic and non-diabetic patients and the relative efficacy of each dose of dabigatran (150 mg bid and 110 mg bid) versus warfarin was evaluated.. Of 18,113 patients in RE-LY, 4221 patients (23.3%) had DM. Patients with DM were younger (70.9 vs. 71.7 years), more likely to have hypertension (86.6% vs. 76.5%), coronary artery disease (37.4% vs. 24.9%) and peripheral vascular disease (5.6% vs. 3.2%); (all p<0.01). Time in therapeutic range for warfarin-treated patients was 65% for diabetic versus 68% for non-diabetic patients (p<0.001). Regardless of assigned treatment, stroke or systemic embolism was more common among patients with DM (1.9% per year vs. 1.3% per year, p<0.001). DM was also associated with an increased risk of death (5.1% per year vs. 3.5% per year, p<0.001) and major bleeding (4.2% per year vs. 3.0% per year, p<0.001). The absolute reduction in stroke or systemic embolism with dabigatran compared to warfarin was greater among patients with DM than those without DM (dabigatran 110 mg: 0.59% per year vs. 0.05% per year; dabigatran 150 mg: 0.89% per year vs. 0.51% per year).. Compared to non-DM patients, AF patients with DM derive a greater absolute risk reduction in embolic events when treated with dabigatran. ClinicalTrials.gov Identifier: NCT00262600.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Comorbidity; Dabigatran; Diabetes Mellitus; Drug Evaluation; Female; Humans; Male; Middle Aged; Risk Factors; Stroke; Warfarin

Ponalrestat (Statil, ICI; Prodiax, Merck Sharp and Dohme) is an aldose reductase inhibitor which is highly protein bound. Ponalrestat markedly displaced warfarin from its protein binding in vitro at a concentration of 500 micrograms ml-1, but not at a concentration of 50 or 100 micrograms ml-1. Twelve diabetic patients (six males), age range 38-65 years, in receipt of chronic stable warfarin therapy, were given ponalrestat (600 mg daily) for 2 weeks in an open trial. A matching placebo tablet was administered for 1 week before and after the active treatment period. Patients were seen ten times (four times during the ponalrestat phase), and during the ponalrestat phase, plasma samples were also taken before and at 3 h after the daily dose of ponalrestat. At none of the visits was there any significant change in prothrombin ratio (INR), plasma total or unbound warfarin concentrations, or percentage protein binding of warfarin. No clinical complications of combination treatment were detected. The maximum ponalrestat concentration observed in the patients was approximately 100 micrograms ml-1. We conclude that no significant interaction between these drugs occurs at the doses of ponalrestat studied.

Topics: Adult; Aldehyde Reductase; Binding, Competitive; Blood Proteins; Chromatography, High Pressure Liquid; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; In Vitro Techniques; Male; Middle Aged; Phthalazines; Protein Binding; Warfarin

Heart failure (HF) is a critical complication in elderly patients with atrial fibrillation (AF) and diabetes mellitus (DM). Recent preclinical studies suggested that non-vitamin K antagonist oral anticoagulants (NOACs) can potentially suppress the progression of cardiac fibrosis and ischemic cardiomyopathy. Whether different oral anticoagulants influence the risk of HF in older adults with AF and DM is unknown. This study aimed to evaluate the risk of HF in elderly patients with AF and DM who were administered NOACs or warfarin.. A nationwide retrospective cohort study was conducted based on claims data from the entire Taiwanese population. Target trial emulation design was applied to strengthen causal inference using observational data. Patients aged  ≥ 65 years with AF and DM on NOAC or warfarin treatment between 2012 and 2019 were included and followed up until 2020. The primary outcome was newly diagnosed HF. Propensity score-based fine stratification weightings were used to balance patient characteristics between NOAC and warfarin groups. Hazard ratios (HRs) were estimated using Cox proportional hazard models.. The study included a total of 24,835 individuals (19,710 NOAC and 5,125 warfarin users). Patients taking NOACs had a significantly lower risk of HF than those taking warfarin (HR = 0.80, 95% CI 0.74-0.86, p < 0.001). Subgroup analyses for individual NOACs suggested that dabigatran (HR = 0.86, 95% CI 0.80-0.93, p < 0.001), rivaroxaban (HR = 0.80, 95% CI 0.74-0.86, p < 0.001), apixaban (HR = 0.78, 95% CI 0.68-0.90, p < 0.001), and edoxaban (HR = 0.72, 95% CI 0.60-0.86, p < 0.001) were associated with lower risks of HF than warfarin. The findings were consistent regardless of age and sex subgroups and were more prominent in those with high medication possession ratios. Several sensitivity analyses further supported the robustness of our findings.. This nationwide cohort study demonstrated that elderly patients with AF and DM taking NOACs had a lower risk of incident HF than those taking warfarin. Our findings suggested that NOACs may be the preferred oral anticoagulant treatment when considering the prevention of heart failure in this vulnerable population. Future research is warranted to elucidate causation and investigate the underlying mechanisms.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Diabetes Mellitus; Heart Failure; Humans; Retrospective Studies; Rivaroxaban; Stroke; Warfarin

The healthcare resource utilization (HRU) and costs of oral anticoagulant-naïve patients with non-valvular atrial fibrillation (NVAF) and diabetes initiated on rivaroxaban or warfarin in the United States (US) has not been previously evaluated.. This retrospective study used data from the Optum's de-identified Clinformatics. After IPTW, 17,881 and 19,274 patients initiated on rivaroxaban and warfarin were included, respectively (mean age: 73 years; 40% female). During 12 months of follow-up, the rivaroxaban cohort had lower all-cause HRU PPY across all components, including lower rates of inpatient stays (RR: 0.84, 95% CI 0.81, 0.88), outpatient visits (RR: 0.67, 95% CI 0.66, 0.68), and 30 day hospital readmission (OR: 0.75, 95% CI 0.66, 0.83; all p < 0.001) compared to the warfarin cohort. Moreover, rivaroxaban was associated with medical cost savings PPY (mean cost difference: - $9306, 95% CI - $11,769, - $6607), which compensated for higher pharmacy costs relative to warfarin (mean cost difference: $5518, 95% CI $5193, $5839), resulting in significantly lower all-cause total healthcare costs for rivaroxaban versus warfarin (mean cost difference: - $3788, 95% CI - $6258, - $1035; all p < 0.001).. Among NVAF patients with diabetes in a real-world US setting, rivaroxaban was associated with lower healthcare costs compared to warfarin.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Diabetes Mellitus; Female; Humans; Male; Patient Acceptance of Health Care; Retrospective Studies; Rivaroxaban; Stroke; United States; Warfarin

Evidence regarding the risks of serious hypoglycaemia for patients with atrial fibrillation (AF) and diabetes mellitus (DM) taking antidiabetic medications with concurrent non-vitamin K antagonist oral anticoagulants (NOACs) vs. warfarin is limited. This study aimed to investigate this knowledge gap.. This retrospective cohort study used nationwide data from Taiwan's National Health Insurance Research Database and included a total of 56 774 adult patients treated with antidiabetic medications and oral anticoagulants between 1 January 2012 and 31 December 2020. The incidence rate ratios (IRRs) of serious hypoglycaemia were estimated for patients taking antidiabetic drugs with NOACs vs. warfarin. Poisson regression models with generalized estimating equations accounting for intra-individual correlation across follow-up periods were used. Stabilized inverse probability of treatment weighting was used to create treatment groups with balanced characteristics for comparisons. Compared to concurrent use of antidiabetic drugs with warfarin, those with NOACs showed a significantly lower risk of serious hypoglycaemia (IRR = 0.73, 95% CI: 0.63-0.85, P < 0.001). In the analyses of each NOAC, patients taking dabigatran (IRR = 0.76, 95% CI: 0.63-0.91, P = 0.002), rivaroxaban (IRR = 0.72, 95% CI: 0.61-0.86, P < 0.001), and apixaban (IRR = 0.71, 95% CI: 0.57-0.89, P = 0.003) showed a significantly lower risk of serious hypoglycaemia than those taking warfarin.. In patients with AF and DM taking antidiabetic drugs, concurrent use of NOACs was associated with a lower risk of serious hypoglycaemia than concurrent use of warfarin.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cohort Studies; Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents; Retrospective Studies; Treatment Outcome; Warfarin

To compare clinical outcomes of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation (NVAF) and concurrent obesity and diabetes.. Patients aged ≥18 years were identified from a healthcare claims database with the following criteria: newly initiating rivaroxaban or warfarin, ≥1 medical claim with a diagnosis of AF, obesity determined by validated machine learning algorithm, and ≥1 claim with a diagnosis of diabetes or for antidiabetic medication. Treatment cohorts were matched using propensity scores and were compared for stroke/systemic embolism (SE) and major bleeding using Cox proportional hazards models.. A total of 9999 matched pairs of NVAF patients with obesity and diabetes who initiated treatment with rivaroxaban or warfarin were included. The composite risk of stroke/SE was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (HR 0.82; 95% CI 0.74-0.90). Risks of ischemic and hemorrhagic strokes were also significantly reduced with rivaroxaban versus warfarin, but not SE. Major bleeding risk was similar between treatment cohorts (HR 0.92; 95% CI 0.78-1.09).. In NVAF patients with comorbidities of obesity and diabetes, rivaroxaban was associated with lower risks of stroke/SE and similar risk of major bleeding versus warfarin.

Topics: Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Embolism; Hemorrhage; Humans; Obesity; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

To compare the risk of diabetes development in patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin.. We conducted a nationwide retrospective cohort study using Taiwan's National Health Insurance Research Database. Adult patients with new onset of AF, treated with NOACs or warfarin between 2012 and 2016, were included. The NOAC cohort was further divided into dabigatran, rivaroxaban and apixaban groups. The primary outcome was incident diabetes requiring treatment with antidiabetic drugs. Fine and Gray subdistribution hazards models were used to estimate the adjusted hazard ratio (aHR). Propensity score matching was performed for each head-to-head comparison.. A total of 10 746 new-onset AF patients were included in our study. During the mean 2.4-year follow-up, NOACs were associated with a lower risk of developing diabetes than warfarin (aHR = 0.80, 95% confidence interval [CI]: 0.68-0.94, P = .007). Subgroup analyses confirmed that dabigatran, rivaroxaban and apixaban each had a reduced diabetes risk. Stratified analyses showed that the lower risk of diabetes associated with NOAC treatment was specific to patients aged 65 years or older (aHR = 0.74, 95% CI: 0.62-0.89, P = .002) and those with good medication adherence (aHR = 0.70, 95% CI: 0.58-0.84, P < .001).. Taking an NOAC was associated with a lower risk of developing diabetes than taking warfarin in patients with AF.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Cohort Studies; Diabetes Mellitus; Humans; Pyridones; Retrospective Studies; Stroke; Warfarin

To evaluate comparative effectiveness and safety of non-vitamin-K antagonist oral anticoagulants (NOACs) versus warfarin in Medicare beneficiaries with non-valvular atrial fibrillation (NVAF) and comorbid diabetes mellitus (DM).. A retrospective cohort study using 2014-2016 5% national Medicare data was undertaken. NVAF patients with DM aged ≥65 years having at least one prescription for NOACs or warfarin between July 2014 and December 2015 were included in the study. Propensity score matching was used to balance demographic and baseline clinical characteristics of patients in two treatment groups. Cardiovascular outcomes including stroke/systemic embolism (SE) and myocardial infarction (MI) were evaluated to measure effectiveness. Assessment of safety outcomes included intracranial hemorrhage (ICH), major gastrointestinal bleeding (MGB), bleeding from other sites (OB) and all-cause mortality. Stratified Cox proportional hazards models were used to estimate hazard ratios for the outcomes in the matched cohort.. The matched sample consisted of 4582 patients (2291 pairs). Compared to warfarin, NOACs had a significantly lower risk of stroke/SE (hazard ratio (HR): 0.373, 95% confidence interval (CI): 0.247-0.564,. Oral anticoagulation therapy with NOACs was found to be more effective than warfarin therapy among older adults with NVAF and comorbid DM.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Gastrointestinal Hemorrhage; Humans; Medicare; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; United States; Warfarin

Patients with diabetes have a higher risk of nonvalvular atrial fibrillation (NVAF), cerebral embolisms and anticoagulant-related intracranial bleeding when compared to nondiabetic patients. Non-vitamin K oral anticoagulants (NOACs) are progressively replacing antivitamin K agents among patients with NVAF. They are as efficacious as warfarin to reduce the risk of cerebral and systemic embolisms while reducing the risk of both severe and cerebral hemorrhages. Four studies reported results of prespecified subanalyses that compared results of efficacy and safety of NOACs (dabigatran, rivaroxaban, apixaban, edoxaban) in patients with and without diabetes, overall with similar results in both subgroups. ENGAGE AF-TIMI 48 is the only trial that reported a significant reduction of severe hemorrhages with edoxaban compared with warfarin in diabetic patients with NVAF.. Les patients avec diabète présentent un risque accru de fibrillation auriculaire non valvulaire (FANV), d’embolies cérébrales et d’hémorragies intra-crâniennes sous anticoagulants par rapport aux patients non diabétiques. Les anticoagulants oraux directs (AODs) remplacent progressivement les agents anti-vitamine K (coumariniques) chez les patients avec FANV. Ils se révèlent aussi efficaces que la warfarine pour réduire le risque d’embolies cérébrales et systémiques, tout en diminuant, comparativement, le risque d’hémorragies sévères et cérébrales. Quatre études ont rapporté les résultats d’une sous-analyse préspécifiée comparant les résultats d’efficacité et de sécurité des AODs (dabigatran, rivaroxaban, apixaban, édoxaban) chez les patients diabétiques et non diabétiques, avec des résultats globalement comparables dans les deux sous-groupes. L’étude ENGAGE AF-TIMI 48 est la seule à avoir rapporté une réduction significative des hémorragies sévères avec l’édoxaban par rapport à la warfarine chez les patients diabétiques.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Humans; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Humans; Stroke; Warfarin

Prevalence of atrial fibrillation (AF) increases with age, along with comorbidities and, thus, polypharmacy. Non-adherence is associated with polypharmacy. This study aimed to identify patients at risk for cardiovascular events according to their pharmacological treatment intensity and adherence. Patients (n = 18,113) with a mean age of 71.5 ± 8.7 years, at high cardiovascular risk were followed between December 2005 until December 2007 for a median time of 2 years. The association between polypharmacy and adherence and their impact on cardiovascular and bleeding events were explored. Adherence was defined as a study drug intake of ≥80%. Patients with more co-medications had a higher body mass index, higher prevalence of hypertension, coronary heart disease, heart failure, and diabetes mellitus (all p < 0.0001) compared to ≤4 or 5-8 co-medications, but no differences in history of stroke (p = 0.68) or transient ischemic attack (p = 0.065). Across all treatments, the adjusted hazard ratios (HRs) increased in patients with more co-medications (≥9 vs ≤4) for all-cause death (HR 1.30; 1.06-1.59), major bleeding (HR 1.65; 1.33-2.05), and all bleeding events (HR 1.44; 1.31-1.59). Yearly event rates were higher in non-adherent than adherent patients for stroke and systemic embolism (SSE) (3.14 vs 1.00), all-cause death (7.76 vs 2.66), major bleeding (6.21 vs 2.65), and all bleeding (28.71 vs 19.05; all p < 0.0001). After an event the patients were more likely to become non-adherent (adherence after SSE 30.3%, after major bleeding 33.4%, after all bleeding 66.7%; all p < 0.0001). The treatment effects were consistent to the overall group in the different polypharmacy groups. In conclusion, polypharmacy and non-adherence are risk indicators for increased adverse cardiovascular and bleeding events. Dabigatran is safe to use across the full spectrum of AF patients, independent of the number of co-medications and adherence. Patients with co-medications and comorbidities require special attention and encouragement to adhere to oral anticoagulation.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Body Mass Index; Coronary Disease; Dabigatran; Diabetes Mellitus; Embolism; Female; Heart Failure; Hemorrhage; Humans; Hypertension; Ischemic Attack, Transient; Male; Medication Adherence; Middle Aged; Polypharmacy; Proportional Hazards Models; Stroke; Warfarin

Diabetes mellitus is a common comorbidity of atrial fibrillation (AF), which can complicate the management of AF. The pharmacology of oral anticoagulants (OACs) have been implicated in pathogenesis of diabetes, but the relationship between different OACs and risk of diabetes remains unexamined. This study aimed to evaluate the risk of diabetes with use of different OACs in AF patients.. Population-based retrospective cohort study using an electronic healthcare database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with AF from 2014 through 2018 and prescribed OACs were included and followed till December 31, 2019. Inverse probability of treatment weighting based on the propensity score (PS) is used to address potential bias due to nonrandomized allocation of treatment. The risks ofdiabetes were compared between different new OAC users using propensity score-weighted cumulative incidence differences (CID).. There were 13,688 new users of OACs (warfarin: n = 3454; apixaban: n = 3335; dabigatran: n = 4210; rivaroxaban: n = 2689). The mean age was 75.0 (SD, 11.2), and 6,550 (47.9%) were women. After a median follow-up of 0.93 years (interquartile range, 0.21-1.92 years), 698 incident diabetes cases were observed. In Cox-regression analysis, dabigatran use was significantly associated with reduced risk of diabetes when compared with warfarin use [HR 0.69 (95% CI 0.56-0.86; P < 0.001)], with statistically insignificant associations observed for use of apixaban and rivaroxaban. The corresponding adjusted CIDs at 2 years after treatment with apixaban, dabigatran, and rivaroxaban users when compared with warfarin were - 2.06% (95% CI - 4.08 to 0.16%); - 3.06% (95% CI - 4.79 to - 1.15%); and - 1.8% (- 3.62 to 0.23%). In head-to-head comparisons between women DOAC users, dabigatran was also associated with a lower risk of diabetes when compared with apixaban and rivaroxaban.. Among adults with AF receiving OACs, the use of dabigatran had the lowest risk of diabetes when compared with warfarin use.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Databases, Factual; Diabetes Mellitus; Factor Xa Inhibitors; Female; Hong Kong; Humans; Incidence; Male; Middle Aged; Pyrazoles; Pyridones; Retrospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Sex Factors; Time Factors; Treatment Outcome; Warfarin

Long-term hyperglycemia in patients with diabetes leads to human serum albumin (HSA) glycation, which may impair HSA function as a transport protein and affect the therapeutic efficacy of anticoagulants in patients with diabetes. In this study, a novel mass spectrometry approach was developed to reveal the differences in the profiles of HSA glycation sites between patients with diabetes and healthy subjects. K199 was the glycation site most significantly changed in patients with diabetes, contributing to different interactions of glycated HSA and normal HSA with two types of anticoagulant drugs, heparin and warfarin. An in vitro experiment showed that the binding affinity to warfarin became stronger when HSA was glycated, while HSA binding to heparin was not significantly influenced by glycation. A pharmacokinetic study showed a decreased level of free warfarin in the plasma of diabetic rats. A preliminary retrospective clinical study also revealed that there was a statistically significant difference in the anticoagulant efficacy between patients with diabetes and patients without diabetes who had been treated with warfarin. Our work suggests that larger studies are needed to provide additional specific guidance for patients with diabetes when they are administered anticoagulant drugs or drugs for treating other chronic diseases.

Topics: Animals; Anticoagulants; Diabetes Mellitus; Glycomics; Heparin; Humans; Molecular Docking Simulation; Rats; Rats, Sprague-Dawley; Retrospective Studies; Serum Albumin, Human; Warfarin

Quality of warfarin therapy in patients with a mechanical prosthetic heart valve (MPHV) has been barely investigated. We analysed determinants of low time in the therapeutic range (TiTR <60%) in 2111 patients with MPHVs from the nationwide PLECTRUM study by the Italian Federation of Anticoagulation Clinics. Overall, 48·5% of patients had a TiTR of < 60%. At logistic regression analysis, arterial hypertension (odds ratio [OR] 1·502, P < 0·001), diabetes (OR 1·732, P < 0·001), heart failure (OR 1·484, P = 0·004), mitral site (vs. aortic) (OR 1·399, P = 0·006), international normalised ratio (INR) ranges of 2·5-3·5 (OR 2·575, P < 0·001) and 3·0-4·0 (OR 8·215, P < 0·001) associated with TiTR < 60%. TiTR is substantially suboptimal in MPHV patients, particularly in higher INR ranges.

Topics: Adult; Age Distribution; Aged; Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Female; Heart Valve Prosthesis; Humans; Hypertension; International Normalized Ratio; Italy; Male; Middle Aged; Myocardial Ischemia; Peripheral Arterial Disease; Retrospective Studies; Smoking; Thrombophilia; Treatment Outcome; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Diabetes Mellitus; Humans; Percutaneous Coronary Intervention; Treatment Outcome; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Diabetes Mellitus; Humans; Percutaneous Coronary Intervention; Treatment Outcome; Warfarin

Studies specifically examining the association between glycated hemoglobin A1c (HbA1c) levels and ischemic stroke/systemic thromboembolism (IS/SE) risk in atrial fibrillation (AF) patients are limited. Here, we investigated the association between HbA1c levels and the risk of IS/SE, as well as major bleeding, among AF patients with or without oral anticoagulants (OACs). We also compared the effectiveness and safety of warfarin and direct oral anticoagulants (DOACs) in different HbA1c categories.. We utilized medical data from a multi-center healthcare provider in Taiwan, which included 34,036 AF patients with serum HbA1c data available within 3 months after AF being diagnosed. Patients were divided into seven study groups according to their HbA1c levels: < 5.4%, 5.4%-5.6%, 5.7%-5.9%, 6.0%-6.4%, 6.5%-6.9%, 7.0%-7.9%, and ≥ 8.0%. The risks of IS/SE and major bleeding were compared among the groups after adjusting for baseline stroke and bleeding risk factors.. Compared with the patients with HbA1c level < 5.4%, IS/SE risk significantly increased at HbA1c levels higher than 6.5% [adjusted hazard ratio (HR): 1.20, 95% confidence interval (CI): 1.00-1.43 for HbA1c level 6.5%-6.9%; 1.32, (95% CI 1.11-1.57) for HbA1c level 7.0%-7.9%; and 1.48 (95% CI 1.25-1.76) for HbA1c level ≥ 8.0%]. These results were generally consistent in AF patients without OACs (n = 24,931). However, among 9105 patients receiving OACs, IS/SE risk was not higher for patients having higher HbA1c levels. The risk of major bleeding was comparable across all HbA1c categories. Compared with warfarin, DOACs were associated with lower risks of IS/SE (adjusted HR: 0.61, 95% CI 0.49-0.75) and major bleeding (adjusted HR: 0.30, 95% CI 0.21-0.42) without interactions across different HbA1c categories (all P interactions > 0.05).. For AF patients, IS/SE risk significantly increased once HbA1c levels exceeded 6.5%, and OACs may attenuate these associations. Compared with warfarin, DOACs were more effective and safer across broad HbA1c categories. Therefore, in addition to prescribing DOACs when indicated, more aggressive glycemic control to achieve an HbA1c level < 6.5% may be considered for eligible AF patients and should be tested in further prospective studies.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Biomarkers; Databases, Factual; Diabetes Mellitus; Factor Xa Inhibitors; Female; Glycated Hemoglobin; Hemorrhage; Humans; Male; Middle Aged; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Stroke; Taiwan; Thromboembolism; Time Factors; Treatment Outcome; Warfarin

Evidence of adverse clinical outcomes for non-vitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation (AF) and diabetes mellitus are limited. We investigated the effectiveness, safety, and major adverse limb events for NOACs versus warfarin among diabetic AF patients.. In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, we identified a total of 20,967 and 5812 consecutive AF patients with diabetes taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. We used propensity-score stabilized weighting to balance covariates across study groups.. NOAC was associated with a lower risk of major adverse cardiovascular events (MACE) (adjusted hazard ratio (aHR):0.88; [95% confidential interval (CI) 0.78-0.99]; P = 0.0283), major adverse limb events (MALE) (aHR:0.72;[95% CI 0.57-0.92]; P = 0.0083), and major bleeding (aHR:0.67;[95% CI 0.59-0.76]; P < 0.0001) compared to warfarin. NOACs decreased MACE in patients of ≥ 75 but not in those aged < 75 years (P interaction = 0.01), and in patients with ischemic heart disease (IHD) compared to those without IHD (P interaction < 0.01). For major adverse limb events, the advantage of risk reduction for NOAC over warfarin persisted in high risk subgroups including age ≥ 75 years, chronic kidney disease, IHD, peripheral artery disease, or use of concomitant antiplatelet drugs.. Among diabetic AF patients, NOACs were associated with a lower risk of thromboembolism, major bleeding, and major adverse limb events than warfarin. Thromboprophylaxis with NOACs should be considered in the diabetic AF population with a high atherosclerotic burden.

Topics: Administration, Oral; Aged; Aged, 80 and over; Amputation, Surgical; Anticoagulants; Atrial Fibrillation; Databases, Factual; Diabetes Mellitus; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Lower Extremity; Male; Middle Aged; Patient Safety; Peripheral Arterial Disease; Retrospective Studies; Risk Assessment; Risk Factors; Taiwan; Time Factors; Treatment Outcome; Vascular Surgical Procedures; Warfarin

Calcific uremic arteriolopathy (CUA) is a highly morbid condition usually found in ESRD patients that has rarely been reported after renal transplantation and renal function restoration. Furthermore, little is known about the optimal management of CUA in this setting. Herein, we report on the clinical case of AB, a 70-year-old woman who developed CUA after renal transplantation and renal function restoration. However, other risk factors for CUA such as diabetes and warfarin treatment, due to mechanical aortic valve implantation, were present. Thirty-eight months after renal transplantation she developed erythema and livedo reticularis in both legs and a gradually enlarging skin ulcer in the right leg. A skin biopsy of the ulcer showed features compatible with the CUA, such as sub-intimal calcification and luminal obstruction of the small dermal arterioles, tissue ischemia and signs of adipocytes degeneration. A multidisciplinary approach was adopted, including medical and non-medical treatments such as surgical debridement and vacuum-assisted closure therapy. Medical treatments included a five weeks course of once a week intravenous infusion of pamidronate and intravenous sodium thiosulfate (STS) at increasing doses. Four months after beginning the therapy with STS, a complete healing of the ulcer on the right leg and the disappearance of the livedo reticularis on the left leg was noted. In conclusion, although rare CUA may develop also in renal transplanted patients, a timely and combined therapeutic approach is essential for its resolutive treatment. Sodium thiosulfate therapy has proven to be effective and tolerated.

Topics: Aged; Anticoagulants; Bone Density Conservation Agents; Calciphylaxis; Chelating Agents; Combined Modality Therapy; Diabetes Mellitus; Female; Humans; Kidney Transplantation; Leg Ulcer; Livedo Reticularis; Pamidronate; Rare Diseases; Risk Factors; Thiosulfates; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Diabetes Mellitus; Humans; Percutaneous Coronary Intervention; Treatment Outcome; Warfarin

Atrial fibrillation (AF) is one of the most common arrhythmias in elderly people. The risk of thromboembolic stroke is increased in AF patients, especially those with diabetes. Anticoagulant therapy, such as warfarin and non-vitamin K oral anticoagulants (NOACs), is recommended for diabetic patients with AF. However, recent guidelines do not preferentially recommend NOACs over warfarin for diabetic patients. Variability of glycemic control in diabetic patients could affect the pharmacokinetics and anticoagulant activity of warfarin, therefore, the risk-benefit balance of warfarin is prone to be compromised in diabetic patients with AF. Furthermore, since warfarin inhibits the vitamin K-dependent gamma-glutamyl carboxylation of proteins, including osteocalcin and matrix Gla protein, use of warfarin may increase the risk of osteoporotic bone fracture and vascular calcification, both of which are the leading causes of morbidity that diminish the quality of life in diabetic patients. Even though the cost of NOACs is high, NOACs may be preferable to warfarin for the treatment of diabetic patients with AF.

Topics: Administration, Oral; Age Factors; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Clinical Decision-Making; Diabetes Mellitus; Female; Humans; Male; Osteoporotic Fractures; Risk Assessment; Risk Factors; Stroke; Thromboembolism; Treatment Outcome; Vascular Calcification; Warfarin

The prevalence of diabetes is growing, and diabetes is an independent risk factor for both atrial fibrillation (AF) and stroke. However, the relative effectiveness and safety of different oral anticoagulants for diabetic patients with non-valvular AF remain unclear. We aimed to compare thromboembolic events, bleeding and mortality in diabetic AF patients treated with rivaroxaban, dabigatran and warfarin.. In diabetic AF patients, dabigatran and rivaroxaban showed a superior or non-inferior effectiveness and safety profile compared with warfarin. Dabigatran was associated with a significantly lower risk of mortality than rivaroxaban.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Comparative Effectiveness Research; Dabigatran; Databases, Factual; Diabetes Complications; Diabetes Mellitus; Female; Humans; Male; Middle Aged; Patient Safety; Proportional Hazards Models; Risk; Risk Factors; Rivaroxaban; Stroke; Taiwan; Thromboembolism; Treatment Outcome; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Humans; Warfarin

Calcific uremic arteriolopathy (CUA) is an often-fatal condition in dialysis patients. The clinical descriptions and treatments of CUA patients have been confined mostly to case reports. We report a comprehensive characterization of CUA and its associated diagnosis, treatment patterns, and outcome.. An internet-based registry collected information about CUA in dialysis patients. Univariate analysis using Cox proportional hazards models estimated hazard ratios of the association between clinical characteristics, laboratory values, and treatments with all-cause mortality.. A total of 117 CUA patients had adequate information for analysis. The majority of patients (56.7%) were diagnosed clinically, with only 32.5% biopsied. Debridement was undertaken in 42.6% of cases. Intravenous sodium thiosulfate (STS) was initiated in 54.7% of patients; most received ≥ 12.5 g of STS (98.3%) for < 3 months (79.7%). Mean parathyroid hormone (PTH) and phosphorus (P) were 459 ± 492 pg/mL and 6.3 ± 2.1 mg/dL, respectively. A total of 24 patients (21.6%, of 111 with information) died, with a median survival time of 2.9 months. In univariate analysis, higher mortality was observed in patients with cardiovascular disease (CVD; HR = 10.47; 95% CI 1.40-78.38), those taking warfarin at time of diagnosis (HR = 2.74; 95% CI 1.16-6.51), and those who had both diabetes (DM) and CVD and who were taking warfarin (HR = 13.41; 95% CI 1.66-109.29).. In real-world clinical practice, there is substantial variability in the diagnosis and treatment of CUA. There is usually only modest derangement of bone and mineral parameters at the time of diagnosis. Death is common. The presence of CVD and use of warfarin may influence clinical outcome after diagnosis of CUA.

Topics: Aged; Anticoagulants; Arterioles; Calciphylaxis; Cardiovascular Diseases; Chelating Agents; Debridement; Diabetes Mellitus; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Proportional Hazards Models; Registries; Renal Dialysis; Risk Factors; Survival Rate; Thiosulfates; Warfarin

Diabetes is an important risk factor for ischemic stroke in non-valvular atrial fibrillation (AF). The aim of the present study was to evaluate temporal trends in ischemic stroke and warfarin use among US Medicare patients with and without diabetes.. In this retrospective cohort study, 1-year cohorts of patients with Medicare as the primary payer over the period 1992-2010 were created using the Medicare 5% sample (excluding patients with valvular disease and end-stage renal disease). International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes were used to identify AF, ischemic and hemorrhagic stroke, and diabetes; three or more consecutive prothrombin time claims were used to identify warfarin use.. Demographic characteristics of subjects in 1992 (n = 40 255) and 2010 (n = 80 314), respectively, were as follows: age 65-74 years, 37% and 32%; age >85 years, 20% and 25%; White, 94% and 93%; hypertension, 46% and 80%; diabetes, 20% and 32%; and chronic kidney disease, 5% and 18%. Among Medicare AF patients with diabetes, ischemic stroke decreased by 71% (1992-2010) from 65 to 19 per 1000 patient-years; warfarin use increased from 28% to 62%. Among patients without diabetes, ischemic stroke decreased by 68% from 44 to 14 per 1000 patient-years, whereas warfarin use increased from 26% to 59%. Approximately 38% of Medicare AF patients with diabetes did not receive anticoagulation in 2010.. Ischemic stroke declined and warfarin use increased similarly in Medicare patients with and without diabetes. Ischemic stroke rates were consistently higher in diabetes patients, validating the inclusion of diabetes in risk calculators. The population of Medicare patients with diabetes who did not receive warfarin deserves future attention.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Comorbidity; Diabetes Mellitus; Female; Humans; Male; Medicare; Retrospective Studies; Risk Factors; Stroke; Time Factors; United States; Warfarin

The combined use of aspirin and oral anticoagulant therapy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) has been questioned due to an increased risk of major bleeding with little to no benefit in preventing ischemic events. (1) To better understand patterns and indications for combined antiplatelet and anticoagulant therapy and identify patients who might reasonably be treated with oral anticoagulant (OAC) therapy alone. (2) To perform an updated literature review regarding the use of combined antiplatelet and OAC therapy in patients with AF and stable CAD. Retrospective review. Patients within the University of Cincinnati Health System with a diagnosis of non-valvular AF, excluding those with acute coronary syndrome or revascularization within the last 12 months. Numbers and indications for combined antiplatelet and anticoagulant therapy and sequence of events leading to the initiation of each. Of 948 patients receiving OAC, 430 (45 %) were receiving concomitant OAC and aspirin. Among patients receiving combined antiplatelet and anticoagulant therapy, 49 and 42 % of patients respectively, had CAD or DM. In a more detailed analysis including chart review of 219 patients receiving combined OAC and aspirin, 27 % had a diagnosis of CAD and 14 % had a diagnosis of DM prior to the development of AF. These patients were initially treated with aspirin. Warfarin was added when they subsequently developed AF but aspirin wasn't discontinued. A surprisingly large proportion of patients (22.8 %) had no obvious indication for dual therapy. Prior myocardial infarction, CAD, vascular disease and DM (among others) increase the likelihood of receiving combined antiplatelet and anticoagulant therapy among patients with AF. A literature review suggests this may lead to increased major bleeding with little benefit in decreasing either AF-related stroke or cardiovascular events.

Topics: Academic Medical Centers; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Coronary Artery Disease; Diabetes Mellitus; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Practice Patterns, Physicians'; Retrospective Studies; Warfarin

To investigate the impact on outcomes of changing treatment guideline recommendations by comparing the proportion of patients with atrial fibrillation (AF) recommended oral anticoagulants (OACs) under the 2011 and 2014 American College of Cardiology/American Heart Association (ACC/AHA) guidelines.. We used the "National Health Insurance Research Database" in Taiwan, which included 354,649 patients with AF from January 1, 1996 through December 31, 2011. Patients with a CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score of 2 or more and a CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65-74 years, female sex category) score of 2 or more were considered to have a definitive indication for receiving OACs according to the 2011 and 2014 ACC/AHA guidelines, respectively.. The percentages of patients with AF recommended OACs increased from 69.3% (n=245,598) under the 2011 guideline to 86.7% (n=307,640) under the new 2014 guidelines, an increment of 17.5% (95% CI, 17.4-17.6). Most women with AF (94.1%) and patients older than 65 years (97.2%) would receive OACs on the basis of the 2014 guidelines. Among patients previously not being recommended OACs in older guidelines, OAC use under the new guidelines was associated with a lower risk of adverse outcomes (ischemic stroke or intracranial hemorrhage or bleeding requiring blood transfusion or mortality) with an adjusted hazard ratio of 0.89 (95% CI, 0.85-0.94).. In this nationwide cohort study, use of the 2014 guidelines led more patients with AF to receive OACs for stroke prevention, and this increased OAC use was associated with better outcomes. Better efforts to implement guidelines would lead to improved outcomes for patients with AF.

Topics: Administration, Oral; Age Distribution; Aged; Anticoagulants; Atrial Fibrillation; Comorbidity; Diabetes Mellitus; Female; Heart Failure; Humans; Hypertension; Insurance Claim Review; Intracranial Hemorrhages; Male; Outcome and Process Assessment, Health Care; Practice Guidelines as Topic; Risk Assessment; Sex Distribution; Stroke; Taiwan; Vascular Diseases; Warfarin

Although controversial, several prior studies have suggested that oral anticoagulants (OACs) are underused in the US atrial fibrillation (AF) population. Appropriate use of OACs is essential because they significantly reduce the risk of stroke in those with AF. In the >2 million Americans with AF, OACs are recommended when the risk of stroke is moderate or high but not when the risk of stroke is low. To quantify trends and guideline adherence, we evaluated OAC use (either warfarin or dabigatran) in a 10-year period in patients with new AF in the Veterans Health Administration.. New AF was defined as at least 2 clinical encounters documenting AF within 120 days of each other and no previous AF diagnosis (N = 297,611). Congestive Heart Failure, Hypertension, Age > 75, Diabetes, and Stroke (CHADS2) scores were determined using age and diagnoses of hypertension, diabetes, heart failure, and stroke or transient ischemic attack during the 12 months before AF diagnosis. Receipt of an OAC within 90 days of a new diagnosis of AF was evaluated using VA pharmacy data.. Overall, initiation of an OAC fell from 51.3% in 2002 to 43.1% in 2011. For patients with CHADS2 score of 0, 1, 2, 3, 4, and 5-6, the proportions of patients prescribed an OAC showed a relative decrease of 26%, 23%, 14%, 12%, 9%, and 13%, respectively (P < .001). Clopidogrel use was stable at 10% of the AF population.. Among US veterans with new AF and additional risk factors for stroke, only about half receive OAC, and the proportion is declining.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Clopidogrel; Dabigatran; Diabetes Mellitus; Female; Guideline Adherence; Heart Failure; Humans; Hypertension; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Risk; Risk Assessment; Stroke; Ticlopidine; United States; United States Department of Veterans Affairs; Warfarin

The difference between left atrial (LA) and systemic coagulation activity in paroxysmal atrial fibrillation (PAF) is unclear.. We enrolled 100 patients with PAF who underwent AF ablation. Warfarin was stopped 1 day before the procedure. LA volume index and LA emptying fraction were measured by 64-slice multidetector computed tomography. Immediately after transseptal puncture, blood samples were simultaneously collected from the LA and systemic circulation (SC). In addition, to evaluate the effect of warfarin on D-dimer levels we recruited an additional 27 PAF patients on continuous warfarin. Even in patients with low CHADS2 scores (mean 0.59 ± 0.68) and during sinus rhythm, the prevalence of positive LA-D-dimer (≥ 0.5 µg/ml) was greater than that of SC-D-dimer (23% vs. 10%, P<0.01). The LA-D-dimer-positive patients had a larger mean LA volume index and reduced LA emptying fraction than the LA-D-dimer-negative patients. Multiple logistic regression analysis revealed that LA volume index was independently correlated with positive LA-D-dimer (odds ratio 2.245, 95% confidence interval 1.194-4.626, P=0.0112). The prevalence of positive LA-D-dimer was significantly lower in patients taking continuous warfarin, than in those on discontinuous warfarin (3.7% vs. 23%, P=0.025).. An enlarged LA volume index was associated with high LA coagulation status in patients with paroxysmal AF. Adequate warfarin control during AF catheter ablation may reduce the prevalence of positive LA-D-dimer.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cardiovascular Agents; Catheter Ablation; Combined Modality Therapy; Comorbidity; Diabetes Mellitus; Female; Fibrin Fibrinogen Degradation Products; Heart Atria; Humans; Hypertension; International Normalized Ratio; Male; Middle Aged; Multidetector Computed Tomography; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Prothrombin Time; Severity of Illness Index; Stroke; Thrombophilia; Thrombosis; Ultrasonography; Warfarin

Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data. We studied the use and outcomes of digoxin in patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).. For this retrospective analysis, we included and classified patients from ROCKET AF on the basis of digoxin use at baseline and during the study. Patients in ROCKET AF were recruited from 45 countries and had AF and risk factors putting them at moderate-to-high risk of stroke, with or without heart failure. We used Cox proportional hazards regression models adjusted for baseline characteristics and drugs to investigate the association of digoxin with all-cause mortality, vascular death, and sudden death. ROCKET AF was registered with ClinicalTrials.gov, number NCT00403767.. In 14,171 randomly assigned patients, digoxin was used at baseline in 5239 (37%). Patients given digoxin were more likely to be female (42% vs 38%) and have a history of heart failure (73% vs 56%), diabetes (43% vs 38%), and persistent AF (88% vs 77%; p<0·0001 for each comparison). After adjustment, digoxin was associated with increased all-cause mortality (5·41 vs 4·30 events per 100 patients-years; hazard ratio 1·17; 95% CI 1·04-1·32; p=0·0093), vascular death (3·55 vs 2·69 per 100 patient-years; 1·19; 1·03-1·39, p=0·0201), and sudden death (1·68 vs 1·12 events per 100 patient-years; 1·36; 1·08-1·70, p=0·0076).. Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of digoxin having these effects. A randomised trial of digoxin in treatment of AF patients with and without heart failure is needed.. Janssen Research & Development and Bayer HealthCare AG.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Death, Sudden; Diabetes Mellitus; Digoxin; Factor Xa Inhibitors; Female; Heart Failure; Heart Rate; Humans; Intracranial Embolism; Male; Morpholines; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Rivaroxaban; Sex Distribution; Stroke; Thiophenes; Vitamin K; Warfarin

To evaluate clinical characteristics and outcome of acute ischemic stroke patients with atrial fibrillation.. Consecutive acute ischemic stroke patients who were hospitalized in the neurology department of General Hospital of Jinan Military Region were prospectively recruited from August 2010 to November 2013.The baseline datum including age, sex, National Institute of Health Stroke Scale (NIHSS), type of Oxfordshire Community Stroke Project (OCSP: total anterior circulation infarct, partial anterior circulation infarction, posterior circulation infarction and lacunar infarction), serum creatinine, serum albumin levels etc.were recorded.Atrial fibrillation (AF) was defined as a history of persistent atrial fibrillation or paroxysmal atrial fibrillation, supported by past electrocardiogram or diagnosed by the attending physicians based on physical examination, electrocardiogram and/or 24-hour electrocardiogram monitoring during hospitalization. Outcome was assessed by modified Rankin Scale (mRS) which was obtained 180 days after stroke by telephone interview (mRS ≤ 2 reflected good prognosis, and mRS>2 reflected unfavorable prognosis), and death defined as all-cause mortality. Multivariate regression model was used to analyze predictors of mortality and disability.. Of the 965 patients included in this study, 113 (11.71%) had AF; valvular AF was observed in 11 patients (9.7%) among them.Only 4 patients with valvular AF and none of the patients with non-valvular AF took warfarin before the stroke event. 14.2% (16/113) acute ischemic stroke patients with AF took aspirin. Compared to patients without AF, patients with AF had a higher NIHSS score on admission (median 11 vs 5, P=0.000); were more often with diabetes (26.55% vs 9.74%, P=0.028), congestive heart failure (12.37% vs 11.03%, P=0.000), prior stroke (31.86% vs 21.83%, P=0.023), total anterior circulation infarct subtype (51.33% vs 19.37%, P=0.000); they were less often smokers (20.35% vs 37.32%, P=0.000), alcohol consumers (13.27% vs 27.58%, P=0.001), partial anterior circulation infarction subtype (24.78% vs 36.74%, P=0.012), lacunar infarct subtype (0 vs 17.61%, P=0.000); they had less often experienced myocardial infarction (11.50% vs 11.74%, P=0.041). AF was a significant independent prognostic factor for long-term poor outcomes (OR=2.227, 95%CI: 1.262-3.933, P=0.006).. Oral anticoagulants are underused in AF patients.Brain infarction patients with AF is more severe than patients without AF; have higher frequency of total anterior circulation infarct subtype, prior stroke and lower frequency of lacunar infarct subtype. AF is a significant independent prognostic factor for long-term poor outcome in patients with acute brain infarction.

Topics: Anticoagulants; Atrial Fibrillation; Brain Infarction; Diabetes Mellitus; Heart Failure; Humans; Myocardial Infarction; Prognosis; Stroke; Treatment Outcome; Warfarin

Acetylsalicylic acid (ASA) and warfarin are used to prevent ischemic cerebrovascular events. They have serious complications including intracranial hemorrhages (ICHs). Warfarin-related intracerebral hemorrhage (ich) incidence is .2%-5% in population that accounts for 10%-12% of all ichs. In this article, we investigated the profile of ASA and warfarin-related spontaneous ICHs in comparison with ICHs without any drug use (WADU) with their clinical, radiological, and biochemical properties.. In all, 486 patients aged 18-101 years with spontaneous ICHs were included. Patients constituted 4 separate groups: users of warfarin, ASA, ASA + warfarin, and WADU. Clinical, neurological, etiological, and radiological data of these patients were compared.. There were 32 patients in warfarin, 58 patients in ASA, and 7 in warfarin + ASA group. Most of the patients were in no drug group (389 patients). The most frequent type of hemorrhage was supratentorial intraparenchymal hemorrhage. The most common accompanying disease was hypertension. The number of female patients was statistically significant in the warfarin group. Glasgow Coma Scale (GCS), accompanying diseases, opening of the hematoma to the ventricle, localization of the hemorrhage, age of the patient, and activated partial thromboplastin time level are all related to the outcome of patients. Warfarin users had worst mortality rate.. Use of warfarin, low GCS score, opening to ventricle, older age, accompanying diabetes, and/or hypertension were worse prognostic factors. It is possible that patients with these unfavorable prognostic factors cannot survive.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Blood Coagulation; Comorbidity; Diabetes Mellitus; Female; Fibrinolytic Agents; Glasgow Coma Scale; Humans; Hypertension; Intracranial Hemorrhages; Male; Middle Aged; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Turkey; Warfarin; Young Adult

The degree of oxidized cysteine (Cys) 34 in human serum albumin (HSA), as determined by high performance liquid chromatography (HPLC), is correlated with oxidative stress related pathological conditions. In order to further characterize the oxidation of Cys34-HSA at the molecular level and to develop a suitable analytical method for a rapid and sensitive clinical laboratory analysis, the use of electrospray ionization time-of-flight mass spectrometer (ESI-TOFMS) was evaluated. A marked increase in the cysteinylation of Cys34 occurs in chronic liver and kidney diseases and diabetes mellitus. A significant positive correlation was observed between the Cys-Cys34-HSA fraction of plasma samples obtained from 229 patients, as determined by ESI-TOFMS, and the degree of oxidized Cys34-HSA determined by HPLC. The Cys-Cys34-HSA fraction was significantly increased with the progression of liver cirrhosis, and was reduced by branched chain amino acids (BCAA) treatment. The changes in the Cys-Cys34-HSA fraction were significantly correlated with the alternations of the plasma levels of advanced oxidized protein products, an oxidative stress marker for proteins. The binding ability of endogenous substances (bilirubin and tryptophan) and drugs (warfarin and diazepam) to HSA purified from chronic liver disease patients were significantly suppressed but significantly improved by BCAA supplementation. Interestingly, the changes in this physiological function of HSA in chronic liver disease were correlated with the Cys-Cys34-HSA fraction. In conclusion, ESI-TOFMS is a suitable high throughput method for the rapid and sensitive quantification of Cys-Cys34-HSA in a large number of samples for evaluating oxidative stress related chronic disease progression or in response to a treatment.

Topics: Aged; Amino Acids, Branched-Chain; Bilirubin; Biomarkers; Chronic Disease; Cysteine; Diabetes Mellitus; Diazepam; Female; Glycation End Products, Advanced; Humans; Liver Cirrhosis; Male; Middle Aged; Models, Molecular; Oxidation-Reduction; Oxidative Stress; Protein Binding; Renal Insufficiency; Serum Albumin; Spectrometry, Mass, Electrospray Ionization; Tryptophan; Warfarin

This study aimed to describe the contemporary aetiology, clinical characteristics and mortality and its predictors in heart failure (HF) in Tanzania.. Design; Prospective observational study. Setting; Cardiovascular Center of the Muhimbili National Hospital in Dar es Salaam, Tanzania. Patients ≥18 years of age with HF defined by the Framingham criteria.. All-cause mortality.. Among 427 included patients, 217 (51%) were females and the mean (SD) age was 55 (17) years. HF aetiologies included hypertension (45%), cardiomyopathy (28%), rheumatic heart disease (RHD) (12%) and ischaemic heart disease (9%). Concurrent atrial fibrillation (AF), clinically significant anaemia, diabetes, tuberculosis and HIV were found in 16%, 12%, 12%, 3% and 2%, respectively, while warfarin was used in 3% of the patients. The mortality rate, 22.4 per 100 person-years over a median follow-up of 7 months, was independently associated with AF, HR 3.4 (95% CI 1.6 to 7.0); in-patient 3.2 (1.5 to 6.8); anaemia 2.3 (1.2 to 4.5); pulmonary hypertension 2.1 (1.1 to 4.2) creatinine clearance 0.98 (0.97 to 1.00) and lack of education 2.3 (1.3 to 4.2).. In HF in Tanzania, patients are younger than in the developed world, but aetiologies are becoming more similar, with hypertension becoming more and RHD less important. Predictors of mortality possible to intervene against are anaemia, AF and lack of education.

Topics: Anemia; Atrial Fibrillation; Comorbidity; Diabetes Mellitus; Educational Status; Female; Heart Failure; HIV Infections; Humans; Kidney Function Tests; Male; Middle Aged; Mortality; Prognosis; Prospective Studies; Tanzania; Tertiary Care Centers; Tuberculosis; Warfarin

To investigate the clinical features and current therapy of atrial fibrillation (AF) of inpatients in Urumqi, China.. The clinical data of inpatients diagnosed with AF from January, 2008 to December, 2012, in 12 hospitals in Urumqi were retrospectively analyzed.. Totally 1 310 AF inpatients were enrolled in this study with the age of (64.8 ± 3.3) years old and a men to women ratio of 1.39. Most patients were in age groups of 61-70 years (26.5%) and 71-80 years (27.6%). More patients with paroxysmal AF were at cardiac function class I-II (75.2%), while more patients with persistent AF were at cardiac function class III-IV (31.0%) (both P values < 0.05). The most common co-morbidities of AF were hypertension (49.2%), coronary heart disease (38.5%), diabetes mellitus (20.1%). Compared with patients of chronic AF, the patients of paroxysmal AF had higher success rates in amiodarone conversation and sinus rhythm maintenance after ablation (44.8% vs 29.9%, 87.5% vs 68.9%, P values < 0.05). Among the 1 310 inpatients, 992 patients (75.7%) received antithrombotic therapy. There were statistically significant differences in CHA2DS2 score and incidence rate of cerebral infarction among patients receiving aspirin, warfarin or rivaroxaban/other anticoagulation drugs [2(1, 3) vs 3(2, 4) vs 3(2, 5) and 6.3% vs 23.8% vs 30.2%, both P values < 0.05].. Our results of AF inpatients' age, gender, related disease distribution, AF types, incidence of stoke, therapeutic and epidemiological features are in accordance with the domestic and abroad reports.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Aspirin; Atrial Fibrillation; China; Comorbidity; Diabetes Mellitus; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Humans; Hypertension; Incidence; Inpatients; Male; Morpholines; Retrospective Studies; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Warfarin

To prevent major hemorrhage during anticoagulation, it is quite important to manage controllable risk factors such as hypertension, diabetes mellitus, smoking habit, and too much alcohol intake. It is also important to avoid dual antithrombotic therapy as long as possible, which increases severe bleeding events. For patients with major bleeding during anticoagulation, we should stop oral medication, stop bleeding by mechanical compression or surgical interventions, and maintain circulation blood volume and blood pressure by appropriate intravenous drip infusion. When intracranial hemorrhage happens, adequate treatment to suppress blood pressure should be provided. Administration of prothrombin complex concentrate (PCC) and vitamin K is effective for urgent reversal of anticoagulation by warfarin. The PCC may be also useful for that by novel oral anticoagulants.

Topics: Administration, Oral; Alcohol Drinking; Anticoagulants; Benzimidazoles; beta-Alanine; Cerebral Hemorrhage; Dabigatran; Diabetes Mellitus; Drug Therapy, Combination; Factor IX; Fibrinolytic Agents; Hemorrhage; Humans; Hypertension; Risk Assessment; Risk Factors; Smoking; Vitamin K; Warfarin

Topics: Aged; Diabetes Mellitus; Drug Interactions; Hospitalization; Humans; Hypoglycemic Agents; Warfarin

The decision to prescribe oral anticoagulant therapy in patients with atrial fibrillation is based on an assessment of the competing risks of ischemic stroke and major bleeding, of which intracerebral hemorrhage (ICH) is the most important type. We sought to determine the comparative importance of risk factors for ischemic stroke and ICH in patients with acute stroke and atrial fibrillation with particular emphasis on risk factors common to both stroke types.. Consecutive patients with acute ischemic stroke or ICH and atrial fibrillation included in the Registry of the Canadian Stroke Network constituted the cohort. Multivariable logistic regression analysis was used to determine the association between baseline risk factors and presentation with ICH versus ischemic stroke. Risk factors included: (1) those previously reported to be risk factors for both ischemic stroke and major bleeding (particularly ICH) ("shared" risk factors, including age, alcohol, hypertension, diabetes mellitus, renal impairment, prior stroke/transient ischemic attack and preadmission dementia); and (2) other risk factors associated with either stroke subtype alone.. A total of 3197 patients presented with atrial fibrillation and acute stroke, of which 12.2% presented with ICH. Of the "shared" risk factors, age (OR, 1.19; 95% CI, 1.06-1.34 per decade) and prior stroke/transient ischemic attack (OR, 1.45; 95% CI, 1.12-1.87) were more associated with ischemic stroke than ICH, whereas a history of hypertension (OR, 0.89; 95% CI, 0.68-1.17), diabetes mellitus (OR 1.23; 95% CI, 0.92-1.64), renal impairment (OR, 1.28; 95% CI, 0.95-1.71), and alcohol intake were not more strongly associated with either stroke subtype.. Of the risk factors known to be associated with both ischemic stroke and ICH in patients with atrial fibrillation, we found that none had a stronger association with ICH. Older age was more strongly associated with ischemic stroke than ICH.

Topics: Age Factors; Aged; Alcohol Drinking; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Canada; Cerebral Hemorrhage; Data Interpretation, Statistical; Dementia; Diabetes Mellitus; Female; Humans; Hypertension; Kidney Diseases; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Recurrence; Registries; Risk Assessment; Risk Factors; Stroke; Warfarin

With over 1.3 billion people, India is estimated to contain three times more genetic diversity than does Europe. Next-generation sequencing technologies have facilitated the understanding of diversity by enabling whole genome sequencing at greater speed and lower cost. While genomes from people of European and Asian descent have been sequenced, only recently has a single male genome from the Indian subcontinent been published at sufficient depth and coverage. In this study we have sequenced and analyzed the genome of a South Asian Indian female (SAIF) from the Indian state of Kerala.. We identified over 3.4 million SNPs in this genome including over 89,873 private variations. Comparison of the SAIF genome with several published personal genomes revealed that this individual shared ~50% of the SNPs with each of these genomes. Analysis of the SAIF mitochondrial genome showed that it was closely related to the U1 haplogroup which has been previously observed in Kerala. We assessed the SAIF genome for SNPs with health and disease consequences and found that the individual was at a higher risk for multiple sclerosis and a few other diseases. In analyzing SNPs that modulate drug response, we found a variation that predicts a favorable response to metformin, a drug used to treat diabetes. SNPs predictive of adverse reaction to warfarin indicated that the SAIF individual is not at risk for bleeding if treated with typical doses of warfarin. In addition, we report the presence of several additional SNPs of medical relevance.. This is the first study to report the complete whole genome sequence of a female from the state of Kerala in India. The availability of this complete genome and variants will further aid studies aimed at understanding genetic diversity, identifying clinically relevant changes and assessing disease burden in the Indian population.

Topics: Anticoagulants; Asian People; Chromosome Mapping; Diabetes Mellitus; DNA Copy Number Variations; Female; Genetic Predisposition to Disease; Genetic Variation; Genome, Human; Genome, Mitochondrial; Haplotypes; Hemorrhage; Humans; Hypoglycemic Agents; India; Metformin; Middle Aged; Multiple Sclerosis; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Warfarin

Acetohexamide is a drug used to treat type II diabetes and is tightly bound to the protein human serum albumin (HSA) in the circulation. It has been proposed that the binding of some drugs with HSA can be affected by the non-enzymatic glycation of this protein. This study used high-performance affinity chromatography to examine the changes in acetohexamide-HSA binding that take place as the glycation of HSA is increased. It was found in frontal analysis experiments that the binding of acetohexamide to glycated HSA could be described by a two-site model involving both strong and weak affinity interactions. The average association equilibrium constant (K(a)) for the high affinity interactions was in the range of 1.2-2.0×10(5)M(-1) and increased in moving from normal HSA to HSA with glycation levels that might be found in advanced diabetes. It was found through competition studies that acetohexamide was binding at both Sudlow sites I and II on the glycated HSA. The K(a) for acetohexamide at Sudlow site I increased by 40% in going from normal HSA to minimally glycated HSA but then decreased back to near-normal values in going to more highly glycated HSA. At Sudlow site II, the K(a) for acetohexamide first decreased by about 40% and then increased in going from normal HSA to minimally glycated HSA and more highly glycated HSA. This information demonstrates the importance of conducting both frontal analysis and site-specific binding studies in examining the effects of glycation on the interactions of a drug with HSA.

Topics: Acetohexamide; Chromatography, Affinity; Chromatography, High Pressure Liquid; Diabetes Mellitus; Glycated Serum Albumin; Glycation End Products, Advanced; Humans; Hypoglycemic Agents; Protein Binding; Regression Analysis; Serum Albumin; Tryptophan; Warfarin

For patients on warfarin therapy, an international normalized ratio (INR) recall interval not exceeding 4 weeks has traditionally been recommended. Less frequent INR monitoring may be feasible in stable patients. We sought to identify patients with stable INRs (defined as having INR values exclusively within the INR range) and comparator patients (defined as at least one INR outside the INR range) in a retrospective, longitudinal cohort study. Occurrences of thromboembolism, bleeding, and death were compared between groups. Multivariate logistic regression models were used to identify independent predictors of stable INR control. There were 2504 stable and 3569 comparator patients. The combined rates of bleeding and thromboembolism were significantly lower in stable patients. Independent predictors of stable INR control were age older than 70 years and the absence of comorbid heart failure and diabetes. Stable patients were significantly less likely to have target INR of 3.0 or higher or chronic diseases. We hypothesize that many patients demonstrating stable INR control could be safely treated with INR recall intervals greater than the traditional 4 weeks.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cohort Studies; Colorado; Comorbidity; Diabetes Mellitus; Drug Monitoring; Female; Heart Failure; Heart Valve Diseases; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Thrombophilia; Treatment Outcome; Venous Thrombosis; Warfarin

Evidence regarding the use of dual antiplatelet therapy and oral anticoagulation (i.e., triple therapy) in acute coronary syndromes (ACS) is limited. We evaluated the characteristics associated with the choice of triple therapy in ACS. Using the Get With The Guidelines (GWTG) Coronary Artery Disease national registry, we studied patients with ACS at 361 sites in the United States from 2004 to 2007. Both univariate analysis and multivariate logistic regression analysis were used to assess the factors associated using triple therapy on discharge. The Generalized Estimating Equation method was used to account for within-hospital clustering in modeling. A total of 86,304 patients presented with ACS during the study period. At discharge, 3,933 patients (4.6%) were prescribed triple therapy, 60,716 patients (70.4%) received dual antiplatelet therapy, 2,348 patients (2.7%) received single antiplatelet therapy plus oral anticoagulation, 19,065 patients (22.1%) received antiplatelet monotherapy, and 242 patients (0.3%) received oral anticoagulation alone. Patients with a history of atrial fibrillation (odds ratio 7.01, 95% confidence interval 6.06 to 8.12; p <0.001), documented new-onset atrial fibrillation (odds ratio 3.76, 95% confidence interval 2.87 to 4.93; p <0.001), or history of atrial flutter (odds ratio 3.38, 95% confidence interval 2.15 to 5.32; p <0.001) were more frequently discharged with triple therapy. In conclusion, for patients with ACS, atrial fibrillation and atrial flutter were most strongly associated with the use of triple therapy; however, this therapy was used less often than dual or single antiplatelet therapy.

Topics: Acute Coronary Syndrome; Aged; Anemia; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Atrial Fibrillation; Atrial Flutter; Clopidogrel; Diabetes Mellitus; Drug Therapy, Combination; Drug Utilization; Female; Humans; Logistic Models; Male; Middle Aged; Patient Discharge; Platelet Aggregation Inhibitors; Registries; Smoking; Stents; Stroke; Stroke Volume; Ticlopidine; United States; Warfarin

Warfarin causes extensive vascular calcification leading to increased systolic blood pressure and pulse pressure in rats, may be associated with increased valvular and coronary calcifications in man, and possibly worsens hypertension in high-risk patients, particularly in those with diabetes mellitus or uncontrolled hypertension. The authors evaluated blood pressure and intensity of antihypertensive therapy over 36 months in a cohort of 58 patients with diabetes and hypertension on warfarin and 58 control subjects with diabetes and hypertension not on warfarin. The results demonstrate that warfarin therapy at conventional doses does not increase systolic blood pressure or pulse pressure in patients with diabetes and hypertension.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antihypertensive Agents; Blood Pressure; Controlled Clinical Trials as Topic; Diabetes Mellitus; Dose-Response Relationship, Drug; Follow-Up Studies; Humans; Hypertension; Longitudinal Studies; Male; Regression Analysis; Research Design; Treatment Outcome; Warfarin

Diabetes mellitus patients after aorto-coronary bypass operation constitute a patient cohort at largely increased risk for secondary coronary events. Antiplatelet agents and antithrombotic agents are applied for secondary prevention. Up to now, secondary prevention has not been addressed specifically in the cohort of diabetic patients after bypass operation. Hence therapeutic recommendations are derived from the global cohort of CAD patients and based on risk assessment rather than on specific data. Since diabetic patients after myocardial infarction are at particularly high risk, combined therapy with clopidogrel and ASS may be considered even with restricted resources in the health system. Oral anticoagulation with coumadin constitutes an effective alternative to dual anti-platelet therapy. Under specific conditions (ventricular aneurysms, EF < 30%, or certain conditions in coronary anatomy) oral anticoagulants should be considered more liberally than currently.

Topics: Anticoagulants; Aspirin; Clopidogrel; Coronary Artery Bypass; Coronary Artery Disease; Diabetes Mellitus; Fibrinolytic Agents; Humans; Platelet Aggregation Inhibitors; Postoperative Complications; Risk Factors; Thrombosis; Ticlopidine; Warfarin

The optimal dose of warfarin varies among individuals, and the prediction of a maintenance dose is difficult. Ethnicity has been reported to influence warfarin dosing.. To quantitate the influence of ethnicity on warfarin dose requirement.. We conducted a retrospective cohort study at a university anticoagulation clinic to evaluate the influence of ethnicity on warfarin dose. Inclusion criteria included age > or = 18 years, target international normalized ratio (INR) 2-3, and warfarin management within the clinic for > or = 3 months with a minimum of 5 clinic visits. We collected clinical and demographic data including age, gender, weight, ethnicity, disease states, concomitant medications, indication, weekly warfarin dosage, and INR. To assess potential confounders, multivariate, repeated-measures regression analysis was used to identify and adjust for variables that may influence the maintenance dose of warfarin.. Of the 345 patients who met the inclusion criteria, 27% were Asian American, 6% Hispanic, 54% white, and 14% African American. The adjusted mean (95% CI) weekly warfarin doses for patients with an INR goal of 2 to 3 were Asian Americans 24 mg (21 to 27), Hispanics 31 mg (25 to 37), whites 36 mg (34 to 39), and African Americans 43 mg (39 to 47) (p < 0.001). Additional factors found to influence warfarin dose requirement included age, weight, concomitant use of amiodarone, and diagnosis of venous thromboembolism.. Warfarin dose requirements vary across ethnic groups even when adjusted for confounding factors, suggesting that genetic variation contributes to interpatient variability.

Topics: Aged; Asian People; Atrial Fibrillation; Black or African American; Cohort Studies; Diabetes Mellitus; Dose-Response Relationship, Drug; Female; Hispanic or Latino; Humans; Hypothyroidism; International Normalized Ratio; Ischemic Attack, Transient; Male; Middle Aged; Retrospective Studies; Stroke Volume; Venous Thrombosis; Ventricular Function, Left; Warfarin; White People

Observations by pharmacists monitoring anticoagulated patients suggested that patients with diabetes often require more frequent international normalized ratio (INR) monitoring than patients without diabetes. The purpose of this investigation was to examine the association between glycemic control and therapeutic anticoagulation control.. Patients with diabetes who were receiving warfarin therapy monitored by the Kaiser Permanente of Colorado Clinical Pharmacy Anticoagulation Service were eligible for inclusion. Patients were included if they had a diagnosis of diabetes mellitus type 1 or 2, aged > or =18 years, and had initiated anticoagulant therapy > or =120 days before their most recent hemoglobin A1C measurement. The primary outcome was the correlation between hemoglobin A1C value and percent of time in the patient-specific INR range. Multivariate analysis was undertaken to regress percent of time in INR range on an A1C value > or =8.0 while adjusting for other possible explanatory variables.. A total of 911 patients with diabetes were included in the study. Subjects with an A1C value > or =8.0 had similar characteristics as those subjects with an A1C value < 8.0. Correlation analysis revealed no relationship between percent of time spent in INR range and A1C value (Spearman Correlation Coefficient = 0.012, p = 0.805). Multivariate analysis revealed no relationship between percent of time spent in INR range and A1C value > or =8.0 (Odds Ratio = 1.00; 95% Confidence Interval = 0.99, 1.01) when adjusting for possible explanatory variables.. For patients with diabetes on warfarin anticoagulation therapy, there is no association between glycemic control and therapeutic anticoagulation control. However, anticoagulation therapy providers should manage these patients with the same diligence and care as patients without diabetes.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cross-Sectional Studies; Diabetes Mellitus; Diabetic Angiopathies; Drug Interactions; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Warfarin

Previous studies have documented sex differences in the management and outcome of patients with cardiovascular disease. However, little data exist on whether similar sex differences exist in stroke patients. We conducted a study to determine whether sex differences exist in patients with acute stroke admitted to Ontario hospitals.. Using linked administrative databases, we performed a population-based cohort study. The databases contained information on all 44 832 patients discharged from acute-care hospitals in Ontario between April 1993 and March 1996 with a most responsible diagnosis of acute stroke. The main outcomes measured consisted of sex differences in comorbidities, the use of rehabilitative services, the use of antiplatelet therapy and anticoagulants (in elderly stroke survivors aged > or =65 years only), discharge destination, and mortality.. Male stroke patients were more likely than female stroke patients to have a history of ischemic heart disease (18.1% versus 15.3%, respectively; P<0.001) and diabetes mellitus (20.1% versus 18. 7%, respectively; P<0.001), whereas female patients were more likely than male patients to have hypertension (33.8% versus 30.0%, respectively; P<0.001) and atrial fibrillation (12.9% versus 10.2%, respectively; P<0.001). There were no sex differences in the usage of in-hospital rehabilitative services. The overall 90-day postdischarge use of aspirin and ticlopidine was similar in stroke survivors aged 65 to 84 years. However, among stroke survivors aged > or =85 years, men were more likely than women to receive aspirin (36. 0% versus 30.7%, respectively; P<0.001) and ticlopidine (9.2% versus 6.8%, respectively; P=0.007). Use of warfarin was similar for the two sexes. Men were more likely than women to be discharged home (50. 6% versus 40.9%, respectively; P<0.001) and less likely to be discharged to chronic care facilities (16.8% versus 25.2%, respectively; P<0.001). The risk of death 1 year after stroke was somewhat lower in women than men (adjusted odds ratio 0.939, 95% CI 0.899 to 0.980; P=0.004). The mortality differences were greatest among elderly stroke patients.. Elderly men are more likely than elderly women to receive aspirin and ticlopidine and equally like to receive warfarin after a stroke. Despite these differences, elderly women have a better 1-year survival after a stroke.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cohort Studies; Comorbidity; Diabetes Mellitus; Female; Humans; Hypertension; Male; Myocardial Ischemia; Ontario; Platelet Aggregation Inhibitors; Retrospective Studies; Sex Characteristics; Stroke; Stroke Rehabilitation; Survival Rate; Ticlopidine; Treatment Outcome; Warfarin

Topics: Anticoagulants; Blood Coagulation; Chromans; Diabetes Mellitus; Drug Interactions; Humans; Hypoglycemic Agents; International Normalized Ratio; Male; Middle Aged; Thiazoles; Thiazolidinediones; Thromboembolism; Troglitazone; Warfarin

Plasma levels of protein S (PS) antigen, both total and free fractions, were measured together with C4b-binding protein (C4bp) and protein C (PC) antigen in 39 patients with disseminated intravascular coagulation (DIC), 34 with liver disease, 17 with collagen disease, 17 with diabetes mellitus, and 51 under stabilized warfarin treatment. In patients with DIC, mean concentrations of total PS and free PS were normal, while PC was reduced and C4bp were elevated. Total PS, free PS, C4bp and PC were all decreased in liver disease, elevated in diabetes mellitus, and normal in collagen disease. In warfarin-treated patients, total PS, free PS and PC were moderately decreased, but the decrease in C4bp was minimal. The concentration of PS correlated positively with PC in liver disease, diabetes mellitus, and during oral anticoagulation, but did not in DIC. These results indicate that PS and PC behave similarly when liver synthetic function is principally affected, but in contrast to PC, PS is hardly consumed during intravascular coagulation.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Antithrombin III; Carrier Proteins; Collagen Diseases; Complement Inactivator Proteins; Diabetes Mellitus; Disseminated Intravascular Coagulation; Factor VIII; Glycoproteins; Humans; Liver Diseases; Middle Aged; Protein C; Protein S; Serum Albumin; von Willebrand Factor; Warfarin

Topics: Blood Coagulation Disorders; Diabetes Mellitus; Humans; Prothrombin Time; Warfarin

Topics: Carbimazole; Chlorpromazine; Diabetes Mellitus; Diazepam; Drug Prescriptions; Epilepsy; Female; Fetus; Heparin; Humans; Hyperthyroidism; Infant, Newborn; Insulin; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Smoking; Streptomycin; Tetracycline; Warfarin

Topics: Anemia, Hemolytic; Animals; Blood Proteins; Blood Sedimentation; Dehydration; Diabetes Mellitus; Dog Diseases; Dogs; Epilepsy, Temporal Lobe; Hematocrit; Nephritis, Interstitial; Pancreatic Diseases; Pancreatic Neoplasms; Warfarin

Topics: Anticoagulants; Blood Coagulation Tests; Diabetes Mellitus; Dicumarol; Drug Synergism; Humans; Insulin; Retrospective Studies; Tolbutamide; Warfarin

Topics: Aqueous Humor; Cataract Extraction; Diabetes Mellitus; Diagnosis, Differential; Eye Neoplasms; Geriatrics; Glaucoma; Humans; Macula Lutea; Macular Degeneration; Pathology; Postoperative Complications; Retinal Detachment; Retinal Hemorrhage; Warfarin

Topics: Anticoagulants; Arrhythmias, Cardiac; Blood Cell Count; Cerebrovascular Disorders; Coronary Disease; Diabetes Mellitus; Dicumarol; Heart Failure; Heparin; Humans; Hypertension; Kidney Diseases; Liver Diseases; Myocardial Infarction; Peptic Ulcer; Pulmonary Embolism; Shock; Thromboembolism; Thrombophlebitis; Thrombosis; Varicose Veins; Warfarin