Warfarin-treated Group Research Articles

The impact of frailty on coagulation and responses to warfarin in acute older hospitalised patients with atrial fibrillation: a pilot study.

The evidence on coagulation changes with frailty is not consistent and clinical studies suggest that frail older people may be at an increased risk of bleeding complications with anticoagulant therapy. This study aims to assess the impact of frailty on coagulation function and on response to warfarin. Inpatients aged over 65years with atrial fibrillation (AF) were recruited. Frailty was determined using the Reported Edmonton Frail Scale. The Overall Haemostatic Potential (OHP) and Calibrated Automated Thrombogram (CAT) were used to globally assess coagulation function. Data of 95 participants were analysed, mean age 85.5 ± 6.2, 40% female, and 50.5% frail. Among participants not on anticoagulants (N = 36), there was an increased fibrin generation and decreased thrombin generation compared to the local established normal ranges in young healthy volunteers; the frail had significantly reduced fibrin generation compared to the non-frail. In the warfarin-treated group (N = 59), there was no difference on coagulation profiles between the frail and the non-frail from any of the coagulation tests. In this cohort of acute hospitalised patients with AF, the observed decreased fibrin generation in the frail may reflect decreased acute phase response as suggested with the lower plasma fibrinogen in that group. There was no difference in coagulation profiles between the frail and the non-frail amongst those taking warfarin. Compared to young healthy volunteers, older inpatients had increased fibrin generation and decreased thrombin generation. The findings reflect the complex interaction between age, frailty, acute illness, and coagulation.

A Comparison of Dabigatran With Warfarin for Stroke Prevention in Atrial Fibrillation in an Asian Population.

The Asian population with atrial fibrillation (AF) have a higher risk of stroke than the caucasian population and a higher risk of intracranial bleeding when anticoagulated with warfarin. There are few real-world studies comparing the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin among Asian patients to assess its outcomes of ischemic stroke and hemorrhagic stroke. A retrospective cohort study of 1000 patients on dabigatran and warfarin from 2009 to 2013. Data were available for 500 patients on dabigatran and 500 patients on warfarin. The average follow-up duration was 315 ± 280 days in the dabigatran group and 355 ± 232 in the warfarin group. The time in therapeutic range (TTR) was 53.2% in the warfarin-treated group, with 32.8% of patients in the subtherapeutic international normalized ratio range of <2. None of the patients in the dabigatran group had ischemic cerebrovascular accident (CVA) compared to 4 (0.8%) patients in the warfarin group, hazard ratio (HR) 0.13, P = .3. There was 1 (0.2%) patient in both dabigatran and warfarin groups with hemorrhagic CVA (HR 1.16, P = .92). There were 3 (0.6%) patients with major bleeding in the dabigatran group compared to 2 (0.4%) patients in the warfarin group (HR 1.57, P = .59). There were similar rates of efficacy for outcomes of ischemic CVA, hemorrhagic CVA, and bleeding when comparing dabigatran with warfarin. Our study shows that despite similar efficacy, suboptimal TTR rates and inconveniences with warfarin demonstrate that NOACs are preferred for stroke prevention in AF.

Extended duration of anticoagulation with edoxaban in patients with venous thromboembolism: a post-hoc analysis of the Hokusai-VTE study

There are few data on the relative efficacy and safety of direct oral anticoagulants, such as edoxaban, compared with vitamin K antagonists during extended therapy for venous thromboembolism. This analysis evaluates the risk-benefit of extended treatment for up to 12 months with edoxaban compared with warfarin among patients enrolled in the Hokusai-VTE study who continued therapy beyond 3 months. The Hokusai-VTE trial (NCT00986154) was a randomised, double-blind, event driven non-inferiority trial in 8292 patients comparing edoxaban with warfarin in the treatment of patients with acute venous thromboembolism. All patients were treated for at least 3 months and treatment was continued for up to 12 months. The outcomes at 12 months were documented in all patients irrespective of treatment duration. 3633 patients treated with edoxaban and 3594 treated with warfarin who completed 3 months of treatment were eligible for this analysis. The primary efficacy outcome was the incidence of adjudicated symptomatic recurrent venous thromboembolism evaluated for each of the time intervals of 3 months, greater than 3 months to 6 months, greater than 6 months to less than 12 months, and at 12 months, as well as the cumulative incidence occurring between 3 and 12 months. The principal safety outcome was the incidence of clinically relevant bleeding (composite of major or clinically relevant non-major bleeding). Both on-treatment and intention-to-treat analyses were done. In the on-treatment analysis, the incidence of recurrent venous thromboembolism at 3 months was 1·1% (0·8-1·4; 44 of 4118 patients) in the edoxaban-treated group versus 1·2% (0·9-1·6; 51 of 4122) in the warfarin-treated group; between greater than 3 months and 6 months, 0·7% (0·3-1·5; eight of 1076) versus 0·5% (0·2-1·1; five of 1084); between greater than 6 months and less than 12 months, 0·2% (0·0-0·8; two of 896) versus 0·8% (0·03-1·7; seven of 851); and at 12 months, <0·1% (0·0-0·3; one of 1661) versus 0·1% (0·0-0·4; two of 1659). In the on-treatment analysis, the cumulative incidence of recurrent venous thromboembolism between 3 and 12 months was 0·3% (95% CI 0·2-1·5; 11 of 3633 patients) in the edoxaban-treated group and 0·4% (0·2-1·7; 14 of 3594) in the warfarin-treated group (HR 0·78, 95% CI 0·36-1·72). The cumulative incidence of clinically relevant bleeding (major or non-major) between 3 and 12 months was 3·9% (95% CI 3·3-4·6; 143 of 3633 patients) in the edoxaban-treated group and 4·1% (3·5-4·8; 147 of 3594 patients) in the warfarin-treated group (HR 0·97, 95% CI 0·77-1·22); cumulative incidence of major bleeding was 0·3% (95% CI 0·2-0·5; 11 of 3633 patients) in the edoxaban-treated group and 0·7% (0·4-1·0; 24 of 3594 patients) in the warfarin-treated group (HR 0·45, 95% CI 0·22-0·92). Similar results were obtained in the intention-to-treat analysis. Extended treatment with edoxaban is effective and associated with less major bleeding than warfarin. Edoxaban once daily provides an attractive alternative to warfarin for patients with venous thromboembolism who require extended treatment for prevention of recurrent venous thromboembolism. Daiichi Sankyo.

Bleeding events with dabigatran or warfarin in patients with venous thromboembolism

Dabigatran was as effective as warfarin for the acute treatment of venous thromboembolism in the RE-COVER and RE-COVER II trials. We compared the incidence of bleeding with dabigatran versus warfarin in pooled data from these studies. The localisation, bleeding severity, and the impact of key factors on the incidence of bleeding, were compared between the dabigatran and warfarin treatment group. Altogether, 2553 patients received dabigatran and 2554 warfarin, each for a mean of 164 days. The incidence of any bleeding event was significantly lower with dabigatran (hazard ratio [HR] 0.70; 95% confidence interval [CI], 0.61-0.79), as was the incidence of the composite of MBEs and clinically relevant non-major bleeding events (HR 0.62; 95% CI, 0.50-0.76). The incidence of major bleeding events (MBEs) was also significantly lower with dabigatran in the double-dummy phase (HR, 0.60; 95%CI, 0.36-0.99) but not statistically different between the two treatment arms when the entire treatment period is considered (HR 0.73 95% CI, 0.48-1.11). Increasing age, reduced renal function, Asian ethnicity, and concomitant antiplatelet therapy were associated with higher bleeding rates in both treatment groups. The reduction in bleeding with dabigatran compared to warfarin was consistent among the subgroups and with a similar pattern for intracranial, and urogenital major bleeding. In conclusion, treatment of venous thromboembolism with dabigatran is associated with a lower risk of bleeding compared to warfarin. This reduction did not differ with respect to the location of bleeding or among predefined subgroups.

Predictive factors for bleeding during treatment with rivaroxaban and warfarin in Japanese patients with atrial fibrillation – Subgroup analysis of J-ROCKET AF

BackgroundResults from the J-ROCKET AF study revealed that rivaroxaban was non-inferior to warfarin with respect to the principal safety outcomes in patients with non-valvular atrial fibrillation. This subgroup analysis evaluated whether non-major clinically relevant bleeding (NMCRB) could be a predictive factor for major bleeding (MB). Other predictive factors for MB were also obtained in both rivaroxaban and warfarin treatment groups. MethodsThe temporal incidence of MB was compared between the rivaroxaban and warfarin treatment groups. Assessment was made whether MB events were often preceded by NMCRB. Univariate and multivariate analyses were carried out to identify any independent predictive factors for MB in both treatment groups. ResultsThe incidences of MB and NMCRB were 18.04% (138/639 patients) in the rivaroxaban arm, and 16.42% in the warfarin arm (124/639 patients). NMCRB preceded MB in only four patients in each treatment group (rivaroxaban: 4/117 and warfarin: 4/98). Multivariate analysis identified predictive factors for bleeding events: anemia with warfarin treatment and concomitant use of antiplatelet agents with rivaroxaban treatment. ConclusionsResults from this subgroup analysis, particularly the fact that there was no repeated or sequential pattern between NMCRB and MB occurrences in both treatment groups, suggests that NMCRB might not be a predictive factor for MB. On the contrary, anemia and concomitant use of antiplatelet therapy were likely predictive factors for bleeding with warfarin and rivaroxaban treatment, respectively.

Abstract 12239: Efficacy and Safety of the Non-vitamin K Antagonist Oral Anticoagulants (NOACs) in Japan: A Retrospective Cohort Study Using the National Database of Health Insurance Claim

Objective: Examine efficacy and safety of anticoagulation (AC) treatment in Japanese Acute hospitals Methods: Insurance claim data of 66, 693 patients who received anticoagulant treatment were extracted from 352 (20%) of hospitals of all 1580 hospitals enrolled in national database of health insurance, Diagnosis Procedure Combination (DPC) database. All the patients received anticoagulant treatment using warfarin and/or non-vitamin K antagonist oral anticoagulants (NOAC) during 10/1/2012 and 9/30/2014. NOACs in this study are: dabigatran, rivaroxaban, and apixaban. We observed incidence of ischemic stroke as efficacy related outcome. We also observed following unfavorable events: intracranial hemorrhage, gastrointestinal hemorrhage, and all-cause death. Outcomes were compared between group of warfarin-treated patients and NOACs-treated patients. Findings: Of 66,693 patients treated with anticoagulants, 50,523(77.3%) were treated with Warfarin, 16,170(24.8%) were with NOACs. Among 66,693 patients, 1,378 patients (2.1%) who were treated with both drugs were excluded for the analysis. The event rate of ischemic stroke was similar between warfarin-treated group and NOACs-treated group 849 (1.68%) vs 245 (1.52%), respectively (p=0.16). On the other hands, unfavorable events were observed significantly more frequently in warfarin-treated group than NOACs-treated group: all-cause death, 4,875(9.6%) vs 724(4.5%), respectively (p&lt;0.001); intracranial hemorrhage, 685(1.4%) vs 94(0.6%), respectively (p&lt;0.001); gastrointestinal hemorrhage, 883 (1.74%) vs 157 (0.97%), p&lt;0.001). Conclusions: This retrospective study based on large-scale national database revealed that efficacy of warfarin and NOACs were equivalent. However, risk of all-cause death and unfavorable bleeding events was higher in warfarin-treated patients than NOACs-treated patients. This study demonstrates that NOACs contribute a beneficial effect on anticoagulation treatment for the patients with atrial fibrillation in the real world.

Healthcare utilization and costs associated with dabigatran compared to warfarin treatment in newly diagnosed patients with non-valvular atrial fibrillation

Purpose:Real-world healthcare resource utilization and costs were compared among patients with non-valvular atrial fibrillation (NVAF) receiving either dabigatran or warfarin.Methods:A retrospective cohort study was conducted using administrative claims data from the United States Department of Defense (DOD) Military Health System. Patients with newly diagnosed AF initiated on dabigatran or warfarin were identified using ICD-9 diagnosis, procedure and drug codes. Patients were observed for 3 months prior to treatment initiation to ascertain a diagnosis of valvular heart disease and 12 months for exclusion of those with a history of anticoagulation therapy. Propensity score matching was used to balance baseline characteristics between the two treatment cohorts. Medical and pharmacy utilization and costs were compared between the dabigatran and warfarin treatment groups for 3 and 12 months following treatment initiation.Results:A total of 1102 patients with newly diagnosed NVAF initiated on dabigatran were matched with corresponding warfarin-treated patients. In the 12 months following initiation of anticoagulation, the mean medical costs for patients initiated on dabigatran were significantly lower than for patients initiated on warfarin (−$6299, p < 0.001), largely due to fewer hospitalizations (−0.162, p = 0.009). While pharmacy costs were higher ($4369, p < 0.001) for dabigatran, overall healthcare costs were significantly lower compared with patients on warfarin (12 months: −$1940, p < 0.001). Mean hospital length of stay between these two groups were similar (6.033 days for dabigatran vs 6.318 days for warfarin, p = 0.139).Conclusion:Despite higher pharmacy costs for NVAF patients initiated on dabigatran vs warfarin, this was more than offset by lower utilization of medical care resources.

Rivaroxaban versus Warfarin in Japanese Patients with Nonvalvular Atrial Fibrillation in Relation to the CHADS2 Score: A Subgroup Analysis of the J-ROCKET AF Trial

Results from a trial of rivaroxaban versus warfarin in 1280 Japanese patients with atrial fibrillation (J-ROCKET AF) revealed that rivaroxaban was noninferior to warfarin with respect to the principal safety outcome. In this subanalysis, we investigated the safety and efficacy of rivaroxaban and warfarin in relation to patients' CHADS2 scores. The mean CHADS2 score was 3.25, and the most frequent scores were 3 and 4. No statistically significant interactions were observed between principal safety outcome event rates and CHADS2 scores with respect to treatment groups (P value for interaction=.700). Irrespective of stratification into moderate- and high-risk groups based on CHADS2 scores of 2 and 3 or more, respectively, no differences in principal safety outcome event rates were observed between rivaroxaban- and warfarin-treated patients (moderate-risk group: hazard ratio [HR], 1.06; 95% confidence interval [CI], .58-1.95; high-risk group: HR, 1.11; 95% CI, .86-1.45; P value for interaction=.488). The primary efficacy end point rate in the rivaroxaban-treated group was numerically lower than in the warfarin-treated group, regardless of risk group stratification (moderate-risk group: HR, .46; 95% CI, .09-2.37; high-risk group: HR, .49; 95% CI, .22-1.11; P value for interaction=.935). This subanalysis indicated that the safety and efficacy of rivaroxaban compared with warfarin were similar, regardless of CHADS2 score.

Efficacy and Safety of Dabigatran Etexilate and Warfarin in “Real-World” Patients With Atrial Fibrillation: A Prospective Nationwide Cohort Study

The aim of this study was to assess the efficacy and safety in an "everyday clinical practice" population of anticoagulant-naïve patients with atrial fibrillation (AF) treated with dabigatran etexilate after its post-approval availability in Denmark, compared with warfarin. Concerns have been raised about an excess of bleeding events or myocardial infarction (MI) among patients treated with the new oral direct thrombin inhibitor, dabigatran etexilate. From the Danish Registry of Medicinal Product Statistics, we identified a dabigatran-treated group and a 1:2 propensity-matched warfarin-treated group of 4,978 and 8,936, respectively. Comparisons on efficacy and safetyoutcomes were made on the basis of Cox-proportional hazards models stratified on propensity-matched groups. Stroke and systemic embolism were not significantly different between warfarin- and dabigatran-treated patients. Adjusted mortality was significantly lower with both dabigatran doses (110 mg b.i.d., propensity-match group stratified hazard ratio [aHR]: 0.79, 95% confidence interval [CI]: 0.65 to 0.95; 150 mg b.i.d., aHR: 0.57, 95% CI: 0.40 to 0.80), when compared with warfarin. Pulmonary embolism was lower compared with warfarin for both doses of dabigatran. Less intracranial bleeding was seen with both dabigatran doses (110 mg b.i.d., aHR: 0.24, 95% CI: 0.08 to 0.56; 150 mg b.i.d., aHR: 0.08, 95% CI: 0.01 to 0.40). The incidence of MI was lower with both dabigatran doses (110 mg b.i.d., aHR: 0.30, 95% CI: 0.18 to 0.49; 150 mg b.i.d., aHR: 0.40, 95% CI: 0.21 to 0.70). Gastrointestinal bleeding was lower with dabigatran 110 mg b.i.d. (aHR: 0.60, 95% CI: 0.37 to 0.93) compared with warfarin but not dabigatran 150 mg b.i.d. The main findings were broadly consistent in a subgroup analysis of dabigatran users with≥1-year follow-up (median follow-up 13.9 months [interquartile range: 12.6 to 15.3 months]). In this "everyday clinical practice" post-approval nationwide clinical cohort, there were similar stroke/systemic embolism and major bleeding rates with dabigatran (both doses) compared with warfarin. Mortality, intracranial bleeding, pulmonary embolism, and MI were lower with dabigatran, compared with warfarin. We found no evidence of an excess of bleeding events or MI among dabigatran-treated patients in this propensity-matched comparison against warfarin, even in the subgroup with≥1-year follow-up.

Effect of Early or Delayed Administration of Warfarin with Heparin on Thrombosis in Pulmonary Thromboembolism

Objective: The aim of this study was to investigate the effect of early or delayed warfarin administration with unfractionated heparin (UFH) on coagulation parameters in pulmonary thromboembolism (PTE). Patients and Methods: This study was performed between November 2006 and July 2007. Thirty-three patients with PTE were sequentially slotted to early (n = 16) and delayed (n = 17) warfarin treatment groups. In the early group, both UFH infusion and warfarin were started simultaneously and in the delayed group, warfarin was added (1–3 days later) based on when partial thromboplastin time reached the therapeutic level with UFH. The proteins C and S, D-dimer, hematocrit levels, and platelet counts for all patients were studied prior to treatment and 6, 24, and 48 h after warfarin treatment. In order to determine the overall effect of early and delayed warfarin treatment on clot formation, a thromboelastogram was performed simultaneously. Results: In both groups, a similar chronological decrease in protein C levels reaching maximum at 24 h with warfarin treatment was observed. However, intragroup or intergroup decreases in protein S levels were not different. On thromboelastogram, INTEM and EXTEM clotting times were significantly prolonged chronologically, but this prolongation was not different between groups. Conclusion: The suppressor effect of warfarin on proteins C and S in the early period of double anticoagulant treatment did not appear to aggravate the risk of thrombosis in patients with PTE in whom warfarin was started simultaneously with UFH.

Management of dental extraction in patients undergoing anticoagulant treatment

Following favourable results from a previous study, a large, multicentre, prospective, case-control study was performed to further assess the incidence of bleeding complications after dental extraction in patients taking oral anticoagulant therapy (OAT). Four hundred fifty-one patients being treated with warfarin who required dental extraction were compared with a control group of 449 non-anticoagulated subjects undergoing the same procedure. In the warfarin-treated group, the oral anticoagulant regimen was maintained unchanged, such that the patients had an International Normalised Ratio ranging between 1.8 and 4, and local haemostatic measures (i.e. fibrin sponges, silk sutures and gauzes saturated with tranexamic acid) were adopted. All the procedures were performed in an outpatient setting. Seven bleeding complications occurred in the OAT group and four in the control group; the difference in the number of bleeding events between the two groups was not statistically significant (OR=1.754; 95% CI 0.510 - 6.034; p=0.3727). No post-operative late bleeds requiring hospitalisation and/or blood transfusions were recorded, and the adjunctive local haemostatic measures were adequate to stop the bleeding. The results of our protocol applied in this large, multicenter study show that dental extractions can be performed easily and safely in anticoagulated outpatients without any modification of the ongoing anticoagulant therapy, thus minimising costs and reducing discomfort for patients.

In Vivo Hemostatic Effect of the Medicinal Plant Extract Ankaferd Blood Stopper in Rats Pretreated With Warfarin

Ankaferd comprises a mixture of Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum and Urtica dioica. Ankaferd Blood Stopper (ABS) has been approved in the management of bleedings. This study aimed to evaluate in vivo hemostatic effect of ABS in rats pretreated with warfarin. Wistar rats (210-270 g) were treated either with warfarin (2 mg/kg) or vehicle (0.9% NaCl) orally before bilateral hind leg amputation. ABS was administered topically to one of the amputed legs. The duration of bleeding and the amount of bleeding were measured to evaluate the hemostatic effect of ABS. Topical ABS administration to amputed leg shortened the duration of bleeding markedly in both untreated and warfarin-treated rats by 31.9% [1.42 min (95% CI: 0.35-2.49)] and 43.5% [5.12 min (95% CI: 2.16-8.07)] respectively. The amount of bleeding in ABS-administered amputed leg showed a decrease by 53.8% in warfarin-treated group. ABS has in vivo hemostatic actions that may provide a therapeutic potential for the management of patients with deficient primary hemostasis in clinical medicine.

A comparison of kaolin-activated versus nonkaolin-activated thromboelastography in native and citrated blood

Thromboelastography can be performed with native or citrated blood (a surrogate to native blood in healthy controls, surgical and cirrhotic patients). Activators such as kaolin are increasingly used to reduce the time to trace generation. To compare kaolin-activated thromboelastography with nonkaolin-activated thromboelastography of native and citrated blood in patients with liver disease, patients undergoing treatment with warfarin or low-molecular weight heparin and healthy volunteers. We studied thromboelastography parameters in 21 healthy volunteers (group 1) and 50 patients, including 20 patients with liver cirrhosis with a nonbiliary aetiology (group 2), 10 patients with primary biliary cirrhosis or primary sclerosing cholangitis (group 3), 10 patients on warfarin treatment (group 4) and 10 patients with enoxaparin prophylaxis (group 5). Thromboelastography was performed using four methods: native blood (kaolin-activated and nonkaolin-activated) and citrated blood (kaolin-activated and nonkaolin-activated). For all thromboelastography parameters, correlation was poor (Spearman correlation coefficient < 0.70) between nonkaolin-activated and kaolin-activated thromboelastography, for both citrated and native blood. In healthy volunteers, in patients with liver disease and in those receiving anticoagulant treatment, there was a poor correlation between nonkaolin-activated and kaolin-activated thromboelastography. Kaolin-activated thromboelastography needs further validation before routine clinical use in these settings, and the specific methodology must be considered in comparing published studies.

Reduction in emergency department visits by patients attending an anticoagulation clinic

Introduction Recent studies suggest that warfarin therapy may be linked to cardiac valve calcification. We aimed to establish whether calcification (C) of valves or other tissue occurs with warfarin and to examine if such C was influenced by treatment duration, age, or gender. Methods We performed a retrospective review of 50 long-term warfarin recipients and 50 untreated controls, matched for age, gender, and comorbidity. For inclusion, patients required a recent echocardiogram (within 18 months) and at least one CT-scan and X-ray. We determined a calcification score (CS) for each patient; one point per site was given for C reported in the aortic, mitral, or tricuspid valve, aorta, coronary and carotid arteries, peripheral vessels, kidney, lung, or other locations. Results The groups were matched for hypertension, diabetes, and coronary disease (P = NS); however, males were younger (64 ± 3 vs. 73 ± 2 years; P = 0.03). Most patients received warfarin for valve replacement (42%) or atrial fibrillation (36%); mean treatment duration, 99 ± 3 months. Analysis revealed five main results; (1) Warfarin-associated CS was increased in cardiac valves (P = 0.01 vs. control) and at each assessed site except the coronary arteries. (2) Total CS was higher with warfarin (2.7 ± 0.3) than controls (1.8 ± 0.2; P = 0.02). (3) CS correlated with warfarin treatment duration (P = 0.03). (4) When all patients were assessed, CS correlated with age for both groups, but was always higher with warfarin (P = 0.02 vs. control). (5) However, this effect was due to warfarin-induced C in males. Total CS was higher for warfarin-treated males (2.4 ± 0.4) versus controls (1.2 ± 0.2; P \ 0.01), irrespective of age (P \ 0.01). In contrast, we found no differences between warfarin-treated and control females. Conclusions Long-term warfarin therapy was associated with tissue calcification not only in valves, but also at other sites. For our entire warfarintreated group, calcification correlated with treatment duration and age; however, the most pronounced increases occurred in males.

Atrial Fibrillation and Thromboembolism

Atrial Fibrillation and Thromboembolism

Aspirin and Warfarin for Thromboembolic Disease After Total Joint Arthroplasty

This study compares the benefits of aspirin and warfarin prophylactic agents for patients with thromboembolic disease after total joint arthroplasty. It is a prospective randomized study of 388 patients having total hip or total knee surgery. All consecutive patients having total hip or total knee surgery were entered into this study and evaluated with preoperative and postoperative ventilation perfusion scans and a postoperative venogram. The aspirin and warfarin treatment groups were compared by size and location of venographically revealed clots and changes in ventilation perfusion scans. The results showed that there was no difference in the size or location of deep venous thrombosis in the aspirin or warfarin treatment groups. The venogram was negative in 44.5% of patients; 28.8% had small ++calf clots, 16% had large calf clots, 3.9% had popliteal clots, and 6.7% had femoral clots. Patients with total knee replacement had a 2.6 times greater incidence of calf deep venous thrombosis than patients with total hip replacement. There was no difference between the aspirin and warfarin groups in the incidence of changes in ventilation perfusion scans (18.9%). There was no difference between the 2 groups in bleeding complications. The results suggest that aspirin and warfarin are equivalent in prophylaxis against thromboembolic disease, as determined by prevention of venographic changes or changes in ventilation perfusion scans.

Effect of low-intensity warfarin anticoagulation on level of activity of the hemostatic system in patients with atrial fibrillation. BAATAF Investigators.

The Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF) demonstrated that low-intensity warfarin anticoagulation can, with safety, sharply reduce the rate of stroke in patients with nonvalvular atrial fibrillation. The beneficial effect of warfarin was presumably related to a decrease in clot formation in the cardiac atria and subsequent embolization. To assess the effect of warfarin therapy on in vivo clotting in patients in the BAATAF, we measured the plasma level of prothrombin activation fragment F1+2. One sample was obtained from 125 patients from the BAATAF; 62 were taking warfarin and 63 were not taking warfarin (control group). The warfarin group had a 71% lower mean F1+2 level than the control group (mean F1+2 of 1.57 nmol/L in the control group compared with a mean of 0.46 nmol/L in the warfarin group; P < .001). F1+2 levels were higher in older subjects but were consistently lower in the warfarin group at all ages. Fifty-two percent of patients in the control group were taking chronic aspirin therapy at the time their F1+2 level was measured. Control patients taking aspirin had F1+2 levels very similar to control patients not taking aspirin (mean of 1.52 nmol/L for control patients on aspirin compared with 1.64 nmol/L for control patients off aspirin; P > .1). We conclude that prothrombin activation was significantly suppressed in vivo by warfarin but not aspirin among patients in the BAATAF. These findings correlate with the marked reduction in ischemic stroke noted among patients in the warfarin treatment group observed in the BAATAF.

Ocular Surgery on Patients Receiving Long-Term Warfarin Therapy

We analyzed data of 50 patients receiving long-term warfarin sodium therapy who underwent ocular surgery between 1982 and 1986. The frequency of hemorrhagic and thrombotic complications was compared in patients in whom anticoagulants were continued, those in whom the anticoagulants were discontinued in the perioperative period, and a group of matched control patients. There were six perioperative hemorrhagic complications in the warfarin-treated group (12%) compared to none in the control group. This difference was significant (P less than .03). However, no significant difference in hemorrhagic complications was seen between patients in whom warfarin sodium was continued and those in whom it was discontinued.

Comparative study of warfarin versus antiplatelet therapy in patients with a St. Jude Medical valve in the aortic position

To determine the necessity of long-term warfarin anticoagulation after St. Jude Medical aortic valve replacement in adults, we evaluated the risks of thromboembolism, valve thrombosis, anticoagulant hemorrhage, and sudden cardiac death in two groups of patients. Group I consisted of 41 patients treated with conventional long-term warfarin therapy. Forty-two patients in Group II were treated primarily with antiplatelet therapy (aspirin, dipyridamole, or both); 17 of these patients received warfarin for a short time postoperatively and seven others received it intermittently during the study period. The groups were similar with respect to age, sex, associated cardiovascular disease, and length of follow-up (mean 29 months per patient). In the warfarin-treated group, three late sudden deaths occurred, one of which was preceded by a cerebrovascular accident, for a cardiac mortality of 2.7% per patient-year. There were eight major nonfatal complications (7.3% per patient-year), of which four were hemorrhagic and four embolic. In Group II, there was one sudden cardiac death (1.1% per patient-year) and four major complications occurred (3.2% per patient-year). Two of the complications were embolic and two were episodes of valve thrombosis, both necessitating reoperation. Although the incidence of serious morbidity in the warfarin-treated group was twice that of patients treated with antiplatelet therapy, there were no statistically significant differences in the rates of sudden death or major complications. These data suggest that antiplatelet therapy may be as effective as warfarin in preventing embolism from the St. Jude Medical valve in the aortic position. Valve thrombosis occurred in two patients, both receiving antiplatelet therapy (2.2% per patient-year). Whether this type of valve failure can be prevented by warfarin remains in question.

Monocyte tissue factor activity in anticoagulant-treated patients

The tissue factor coagulant activity of peripheral blood monocytes was measured in 20 patients on long-term anticoagulant treatment with warfarin and in 21 healthy individuals. Contrary to expectations, tissue factor activity was not reduced in the warfarin-treated group and was, in fact, elevated in several patients. No relationship existed between the daily warfarin dose or the degree of prolongation of the prothrombin time and the monocyte tissue factor activity. These results indicate that monocyte tissue factor activity is not necessarily reduced to below normal levels with warfarin treatment.