Anticoagulation therapy in patients with chronic atrial fibrillation: a retrospective claims data analysis.

OBJECTIVES: This study assessed the risk of thrombo embolic events and bleeding complications among atrial fibrillation patients. METHODS: A cohort of patients with chronic non-valvular atrial fibrillation were identified from medical claims (diagnosis codes 427.31 and 427.32). Subjects were identified from 1 January 1998-31 December 2000 and were continuously enrolled for 6 months prior to the first occurring atrial fibrillation medical claim. Cox proportional hazards analysis with time varying covariates was used for the event analysis. RESULTS: Of 6764 subjects retained for analysis, 3541 (52.4%) were exposed to warfarin. Adjusting for baseline characteristics, warfarin exposure was associated with lower likelihood of an arterial thromboembolic event compared to no exposure (HR: 0.710, CI: 0.540-0.934). No benefit was found in the use of warfarin in the prevention of intracranial events (HR: 1.119, CI: 0.929-1.349). Use of warfarin increased the risk of minor bleeding events (HR: 3.600, CI: 2.537-5.109), and all bleeding events (HR: 1.502, CI: 1.289-1.749). CONCLUSIONS: The risk of arterial thromboembolic events was associated with warfarin exposure as expected. An increase in the risk of minor and total bleeding events among patients treated with warfarin was observed. The results of this study suggest that there may be a gap between the clinical trial and coagulation clinic performance of warfarin in reducing the risk of thromboembolic events versus what is achievable in general practice.

Plasma cross-linked fibrin degradation products fraction D in patients undergoing elective abdominal surgery.

In 18 patients undergoing major abdominal surgery we measured the plasma D-dimer concentration (EIA d-dimer kit) preoperatively, postoperatively, and on postoperative day 1, 3, 4, 5, and 6. The patients received thromboembolic prophylaxis with low-molecular weight heparin. All patients were screened with the 125I-fibrinogen uptake test. Preoperatively, the median plasma D-dimer concentration was 500 ng/ml (200-3200 ng/ml) rising to 1800 ng/ml (500-4600 ng/ml) (p less than 0.05) immediately postoperatively. The plasma D-dimer level increased further during the following days to a maximum of 4800 ng/ml (1600-8600 ng/ml) on the 6th postoperative day (p less than 0.01). One patient developed deep-venous thrombosis. The plasma D-dimer concentration of this patients was within the range of the other patients. In conclusion, the EIA D-dimer test does not seem to be a potential screening procedure for postoperative thrombosis.

Thrombin-antithrombin III-complex & fibrin degradation products in plasma: surgery and postoperative deep venous thrombosis.

Thrombin-antithrombin-III complexes (TAT) & D-dimer in plasma, and fibrin(ogen) degradation products (FDP) in serum, were measured in 48 patients subjected to total hip arthroplasty. Blood samples were collected on days -1, 0, 1, 3, 7 and 10. Five patients developed postoperative deep vein thrombosis (DVT) diagnosed by venography. A characteristic pattern of TAT and D-dimer secondary to surgery was demonstrated. A poor correlation was found between ELISA- and latex-D-dimer concentrations after the operation. Patients with DVT had significantly higher TAT-levels preoperatively, and on day 0, 7 and 10. The concentration of FDP was significantly elevated in patients with DVT on day 7 and that of ELISA D-dimer on days 0 & 10. None of the assays are clinically valuable for purposes of postoperative screening for DVT. The preoperative plasma TAT concentration may represent a valuable predictive marker of postoperative DVT.

Components of coagulation and fibrinolysis during thrombosis prophylaxis with a low molecular weight heparin (Enoxaparin) versus Dextran 70 in hip arthroplasty.

In a prospective randomized study heptest, thrombin-antithrombin complexes (TAT), D-dimer, and t-PA:ag were analysed pre- and postoperatively in 206 consecutive patients undergoing hip arthroplasty during thromboprophylaxis with either a LMW heparin (Enoxaparin) or Dextran 70. Deep vein thrombosis (DVT) developed in 6 of 102 (6%) Enoxaparin and in 21 of 104 (20%) Dextran patients diagnosed by bilateral phelobography. In the Enoxaparin group heptest showed a significant increase from the pre- to the postoperative level opposed to a significant decrease in the Dextran group. Postoperative levels of TAT, D-dimer, and t-PA:ag were significantly increased in both groups, however, TAT was significantly higher in patients in the Dextran group than in the Enoxaparin patients. D-dimer was significantly higher in Dextran patients with DVT postoperatively compared with patients without DVT. No differences concerning TAT or t-PA:ag were observed between patients with and without DVT in any of the groups.

Resection of the first rib, following deep arm vein thrombolysis in patients with thoracic outlet syndrome.

In order to evaluate, the prophylactic effect of first rib resection in patients with fibrinolytic recanalised deep arm vein thrombosis, we present our experience with 21 patients. After recanalisation 12 had phlebographic signs of venous compression in the costoclavicular space, with the arm in the normal position. This fulfills the requirements for thoracic outlet syndrome (TOS). In 60 normal persons without symptoms of TOS none had phlebographic signs of venous compression with the arm in normal position. This difference is significant. In the 12 patients TOS was suspected was to be the underlying cause of rethrombosis and first rib resection was performed. Two patients with TOS had rethrombosis before first rib resection could be performed. At follow up 1 to 6 years after the thrombosis no rethrombosis was found. TOS and deep arm vein thrombosis is rare. Controlled studies are not available. We advocate first rib resection in patients with successful fibrinolysis and TOS in order to avoid rethrombosis.

[Venous thromboembolic disease and oral contraceptives]. / Venøs trombo-embolisk sygdom og p-piller.

PIP: Ever since 1961, there has been discussion on possible thromboembolic effects from the use of oral contraceptives. The purpose of this Danish study was to determine if birth-control pill users did have an increased risk of venous thromboembolic disease (VTD), including deep venous thrombosis and pulmonary embolism. In previous research, morbidity from VTD has been found to show a great variance, as high as 1/330 woman years in 1 study to as low as 1/5,000 woman years in another. In these studies no significant difference was found between users and non-users of oral contraceptives. Only in 1 study was there found to be increased morbidity from VTD among pill users: 1/5,200 woman years, compared with 1/35,000 woman years for non-pill users. As a possible explanation of the pill's effect, several studies have demonstrated a rise in certain coagulation factors, increased fibrinogen and lowered antithrombin III. In the present study, medical records of all women aged 34 or under who had been referred to a Copenhagen hospital between 1981 and 1983 for treatment of phlebographic-or lungescintographic-confirmed VTD were investigated. After controlling for exclusion factors, there remained 35 test subjects between the ages of 16 and 34 (median age 22). Of the 22 cases of known etiology, 16 suffered from iatrogenic VTD. Of 13 women who suffered from VTD of unknown etiology, 69% were pill users, compared with only 29% (a significant difference) in a background-population interview study conducted in Denmark during 1983. With a known disposition to VTD, oral-contraceptive usage meant a relative risk of 0.9 for developing the disease, which figure conforms well with other cited research (in which the risk factor varied from 0.4 to 3.8).^ieng

[Prevention of postoperative thrombosis with low-molecular-weight heparins]. / Forebyggelse af postoperativ trombose med lavmolekylaere hepariner.

To evaluate the efficacy and safety of low molecular weight heparins (LMWHs) in thromboprophylaxis, 28 orthopaedic trials and 38 trials of patients undergoing general or gynaecological surgery were studied and subjected to a partial meta-analysis. In orthopaedic surgery the LMWHs were superior to placebo/dextran, and were at least as efficient as unfractionated heparin (UH) in the prevention of deep venous thrombosis (DVT). Compared with UH, one of the LMWH preparations significantly reduced the total incidence of DVT. The rate of non-fatal pulmonary embolism (PE) was 0.5% in the LMWH group and 1.2% among the controls receiving UH, dextran or vitamin K-antagonists. Seven orthopaedic patients died from PE (0.14%), none of whom received LMWH. In general surgery, the LMWHs were at least as efficient as UH with a trend towards a lower risk of pulmonary embolism. Compared with UH, LMWHs did not reduce the postoperative mortality rate, nor did they cause haemorrhage. LMWHs provide a safe and efficient prophylaxis by administration once daily.

[A prospective controlled study of vagotomy in the treatment of duodenal ulcer. Results after 11-15 years]. / Prospektiv kontrolleret undersøgelse of vagotomi ved behandling af duodenalt ulcus. Resultater efter 11-15 år.

A prospective, randomized, controlled trial was conducted to compare truncal vagotomy and drainage (TV), selective vagotomy and drainage (SV) and parietal cell vagotomy (PCV) as elective treatment for duodenal ulcer. Between 11 and 15 years post-operatively, 248 patients were available for study of the recurrent ulceration rate by a life table method and 197 patients could be studied with regard to post-vagotomy symptoms. The recurrent ulcer rates were TV 28.5%, SV 37.4% and PCV 39.3%. These differences were not statistically significant. There was no significant difference in the Visick gradings among the three groups either before or after treatment of the failures. About two-thirds of the patients in each group were finally satisfied with their operation, often after second operations or prolonged medical treatment.

[Presence of pulmonary emboli in Danish autopsy material]. / Forekomsten af lungeemboli i et dansk obduktionsmateriale.

Two hundred and ten patients with verified pulmonary emboli (LE) at autopsy were assessed retrospectively. These patients comprised 13% of all those submitted to autopsy. LE was the primary cause of death, a contributory cause of death or an incidental finding in 35%, 31% and 34%, respectively, of the cases. Two thirds of the lethal cases were not recognized prior to autopsy. LE was preceded by medical conditions and operation with subsequent immobilization in 55% and 22% of the cases, respectively. Out of these, it is estimated that 17% of the medical patients and 56% of the surgical patients would have had a good prognosis if LE had not occurred. If foreign results can be applied to Danish conditions, approximately 1,400 fatal cases of LE should occur in Denmark per annum. This review confirms that the actual Danish figures are of this magnitude, at least, as approximately 1,500 lethal cases must be assumed to occur per annum solely among patients dying in hospital. In 1986, a total of 278 cases of LE were stated as the primary cause of death on the death certificates. Despite the limitations of a retrospective investigation, it is concluded that the vital statistics of the Danish Board of Health underestimate the genuine number of cases. The range of indications for prophylaxis of thrombosis is possibly too narrow. LE should be considered in the differential diagnosis more frequently, particularly in elderly immobilized patients.

Evaluation of hospitalization and follow-up care costs among patients hospitalized with ACS treated with a stent and clopidogrel.

OBJECTIVE: This retrospective claims study was performed to evaluate the initial and subsequent healthcare costs in patients with acute coronary syndrome (ACS) who had been treated with stent placement and clopidogrel following discharge from the hospital. METHOD AND RESULTS: This was a retrospective, administrative claims-based analysis from a large, geographically diverse US managed care plan affiliated with i3 Innovus. Study subjects were commercially insured enrollees, aged > or = 18, who were hospitalized for ACS between 1 January 2000 and 31 December 2004 with a stent placed, and had at least one filled prescription for clopidogrel within 7 days of discharge from the index hospitalization. Of the 9135 subjects included in the cost analysis, 2241 subjects experienced a subsequent event. On average, subjects with a second event incurred $32,495 more in medical costs over 2 years and $39,742 more in medical costs over 3 years versus those who did not have a second event. Excluding ischemic hospitalizations, subjects with a second event incurred $7257 and $9724 more in medical costs than patients without a second event during the 2 and 3 years following discharge from the index hospitalization, respectively. CONCLUSIONS: Significant cost increases were observed among patients who had a subsequent hospitalization for an ischemic event compared to those without a subsequent hospitalization. Cost increases were still present after excluding costs of the ischemic hospitalizations. The findings of this study must be considered within the limitations of database analysis as claims data are collected for the purpose of payment and not research.

Patterns of use of antithrombotic therapy and quality of anticoagulation among patients with non-valvular atrial fibrillation in clinical practice.

We conducted a retrospective cohort study of thromboprophylaxis rates and the quality of anticoagulation control among patients with atrial fibrillation (AF) using a large, geographically diverse database of electronic medical records. The study population consisted of 13,709 AF patients treated in US outpatient physician practices. Approximately two-thirds were prescribed warfarin alone or in combination with another drug. Older patients, males, and those with congestive heart failure (CHF) or prior stroke were more likely to receive antithrombotic therapy. Among 6454 patients treated with warfarin who had at least two valid prothrombin time/international normalised ratio test results, approximately half of study days were spent in target range. Female sex, CHF and residence in the Northeast were associated with more time out of range. Our study confirms that, in routine medical practice, warfarin is not prescribed for substantial numbers of eligible patients, and anticoagulation control with warfarin is suboptimal for many of those at risk for thromboembolism.

The oral contraceptive user.

The use of oral contraceptives (OC) has been correlated to several diseases, primarily thromboembolic conditions. Whether these correlations represent a causal relationship or a mere statistical correlation based on other variables, depends on whether users of OC differ in other respects from women in fertile age not using OC. We interviewed 519 Danish women, 15-45 years old and selected at random, concerning present and past use of OC, age, occupation, years of schooling, marital status, income, smoking habits, urbanization, and their opinion on the postulated thrombotic risk among users of OC. The data were analysed by methods for multivariate contingency tables. Opinions on the thrombotic risk, age, smoking habits and, to a lesser degree, regarding income, were directly correlated to the oral contraceptive use. There was no direct interaction between the use of OC and the other variables. Users of OC were younger and smoked more than the non-users and were of the opinion that the use of OC implied only minor thrombotic risk, or none at all.

PIP: Although numerous studies have identified an association between oral contraceptive (OC) use and thromboembolic disease, it has not been established whether this represents a causal relationship or is a result of other variables. To determine whether OC users differ from nonusers in significant ways, 519 randomly selected Danish women 15-45 years of age were surveyed about past and present OC use, age, occupation, educational status, marital status, income, urbanization, and their beliefs about the risks of OC use. 23.7% of study subjects were current OC users. OC users were significantly younger than nonusers and former users; 58% of the OC users surveyed were 15-25 years of age. There was also a significant correlation between OC use and smoking; 58% of users compared with 41% of never users were cigarette smokers. OC users tended to consider the pill to be less thrombogenic. 66% of current OC acceptors believed the pill was completely nonthrombogenic compared with 41% of ex or never-users. There was no direct interaction between OC use and the other variables examined. These 3 significant associations suggest that OC users are not entirely representative of fertile women in general. Moreover, it is possible that factors not explored in the current study (e.g., life-style and stress level) have an important impact on thromboembolic risk, regardless of OC use.

Peritoneal lavage for the evaluation of patients with equivocal signs after abdominal trauma.

The value of peritoneal lavage (PL) in the evaluation of 82 patients with equivocal signs after abdominal trauma was studied. The closed technique using an Intracatch (R) was employed. Fifty-four patients had blunt trauma, the predictive value of a positive PL was 86% and the predictive value of a negative PL was 94%, accuracy 94%. Twenty-eight patients had stab wounds, the figures in this group were 100%, 92% and 93%. No complications were seen. There were no retrieval of lavage fluid in 10% of the cases. PL with the closed Intracath (R) technique has the same diagnostic certainty as other methods, but is much quicker to perform and has no complications.

Cost-benefit analysis of prophylaxis against deep vein thrombosis in surgery.

A cost-benefit analysis was performed based on the incidence of postoperative thromboembolic complications, the cost of prophylaxis, and the cost of treating the complications. It was determined that prophylaxis against thromboembolic complications in both general surgery and total hip replacement, with either standard heparin or low molecular weight heparin, saves lives as well as reduces health care costs.

Prophylaxis of postoperative thromboembolism with low molecular weight heparins.

To evaluate the thromboprophylactic use of low molecular weight heparins (LMWHs), publications from 27 orthopaedic trials and 35 studies of patients undergoing general or gynaecological surgery were scrutinized and subjected to a partial meta-analysis. In orthopaedic surgery, LMWHs were superior to placebo or dextran and at least as efficient as unfractionated heparin in the prevention of deep vein thrombosis (DVT). Compared with unfractionated heparin, one of the LMWH preparations significantly reduced the total incidence of DVT. The rate of non-fatal pulmonary embolism was 0.49 per cent in patients receiving LMWH and 1.22 per cent in controls. Seven orthopaedic patients (0.15 per cent) died from pulmonary embolism, none of whom received LMWH. In general surgery, the LMWHs were at least as efficient as unfractionated heparin, with a trend towards a lower risk of pulmonary embolism with the former. Compared with unfractionated heparin, LMWHs did not reduce the postoperative mortality rate, nor did they cause haemorrhage. LMWHs provide safe and efficient prophylaxis by administration once daily.