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.

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.

[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.

The development in attitudes towards thromboprophylaxis in Danish surgical departments during a ten year period.

OBJECTIVE: To summarize and evaluate the progress in the current practices of thromboprophylaxis (TP) in Danish surgical departments. DESIGN: Summary of three questionnaire surveys in 1981, 1985 and 1990. SUBJECTS/SETTING: Hospital departments performing general, orthopaedic or gynaecological surgery in Denmark. MAIN OUTCOME MEASURES: Development or routine employment of TP, standard instructions for TP, indications and methods for TP. RESULTS: Replies were obtained from 85%-92%. During the period the overall use TP increased from 89% of the departments in 1981 to 93% in 1985 to 96% in 1990 (p = 0.03). The use of TP according to standard instructions increased from 50% over 54% to 68% (p = 0.001). Heparin is the drug of choice in 95% and graded compression stockings in 70% of the departments. Only 36% of the departments routinely use TP in emergency surgery. CONCLUSIONS: The development in attitudes towards TP in Denmark complies with the scientific evolution. Methods and indications correspond with the recommendation of the literature and international consensus conferences. However, the low rate of TP in emergency surgery is unsatisfactory, and the use of acetylsalicylic acid as postoperative venous thromboprophylaxis should stop. The authors emphasize the introduction of firm standard instruction for TP in all surgical department. A continuous evaluation of the use of TP in Danish surgical department by means of quality assurance studies is recommended.

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.

Potential influence of observer variation in thromboprophylactic trials.

In order to investigate the influence of the interpretation of a postoperative venography, used as the scientific tool in a thromboprophylactic trial, twelve different evaluations of the same venography have been compared. Two hundred and nineteen patients, undergoing total hip replacement, fulfilled a randomized trial evaluating two different prophylactic regimens. Bilateral venography was performed 7-11 days after surgery, and the result of venography was defined as with or without deep venous thrombosis (DVT), irrespective of the location of a thrombus. The venograms were evaluated five times by different interpreters, and the criteria for the presence of DVT were recorded whether or not thrombi in minor veins were present. The incidences of DVT in the two prophylactic groups varied from 2.7 to 20.3% and from 13.5 to 34.2%, respectively, according to the diagnostic criteria. However, the risk reduction between the two groups was almost constant, no matter which type of evaluation was applied (7.9-15.1%), and was statistically significant at the 5% level in all but 4 of the 12 evaluations. It is concluded that despite uniformity in patient selection, the incidence of DVT is not uniform, even though it is stated that venography is used as the end point. The obvious interobserver variation did not change the conclusion when two regimens are compared in a specific randomized study.

Phlebography as the gold standard in thromboprophylactic studies? A multicenter interobserver variation study.

In 241 patients with total hip arthroplasty and entering a study on thrombosis prophylaxis, phlebography was adequately performed in 451 legs 7 to 11 days after surgery. The phlebograms were primary evaluated by 4 independent observers, and finally a consensus of the images in which disagreement primarily occurred was obtained. The diagnosis of thrombosis in the 4 primary observations varied between 65% and 83% (mean 70%) and the agreement on a negative diagnosis between 97% and 99% (mean 98%). Taking into account agreement by chance, kappa-values varied from 0.60 to 0.83 when the 6 different pairs of observations were compared. When comparing the primary evaluations with the final consensus, agreements on positive diagnosis varied between 70% and 90% (mean 80%) and on negative diagnosis between 97% and 99% (mean 98%). Kappa-values varied from 0.68 to 0.90. The factor of uncertainty in evaluation of phlebography may have to be considered when studies on postsurgical thromboprophylaxis are planned.

Biologic tolerance of two different low molecular weight heparins.

Heparin preparations have been used for prophylaxis and treatment of deep vein thrombosis for many years. Several biologic effects of heparin are known. Since 1978, there have been several reports about reversible elevation in serum values of AST and ALT in patients and healthy volunteers given heparin in small and high doses. Few studies report similar events in patients given LMW heparins. Results of two randomized studies (A and B) comprising 456 patients undergoing THR are presented. Two different compounds of LMW heparin (Logiparin or Enoxaparin) were used for thromboprophylaxis. Significant elevation during the postoperative period of AST and AP in study A, and AST, ALT, AP, LDH, and CK in study B were demonstrated in patients given LMW heparins in both studies. In study A the percentages of patients with normal preoperative values who reached pathologic values were 35% for AST and 15% for AP. In study B the percentages of patients with normal preoperative values who reached pathologic values were 36% for AST, 17% of ALT, 14% for AP, and 36% for LDH. The possible biologic mechanisms and the clinical perspectives are discussed. In all cases the changes in the liver enzymes returned to preoperative levels within 14 days.

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.

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 deep venous thrombosis after acute abdominal operation.

Two hundred and forty-five patients who underwent acute extensive abdominal operations were randomized into three regimens to achieve optimal prophylaxis of postoperative thromboembolic complications. All of the patients were screened by the 125I-fibrinogen uptake test for seven days and if the phlebographic findings were positive. Of 81 patients receiving low dose heparin, 12 had thromboembolism. Of 79 receiving a combination of low dose heparin and graded compression stockings, two had thromboembolism, and of 85 receiving a combination of dextran and graded compression stockings, 13 had this complication. This difference is significant in favor of the second treatment (p = 0.013). It is concluded that the combination of low dose heparin and graded compression stockings is an effective way to prevent thromboembolism after acute abdominal operations.

Fatal pulmonary embolism associated with surgery. An autopsy study.

The records of all autopsies performed at two major Danish hospitals in 1986 were reviewed in order to analyze cases of fatal pulmonary embolism. There were 2,609 hospital deaths and 1,603 post mortem examinations. Pulmonary embolism was the primary cause of 74 deaths, 16 of which were postoperative. The median age of these ten men and six women was 72 years. In nine of the 16 cases the prognosis would have been favorable had embolism not occurred. Only three of the 16 had received thromboembolic prophylaxis. Four of the deaths from embolism occurred less than 24 hours after surgery, five within 7 days and seven between postoperative days 7 and 30. The estimated incidence of fatal pulmonary embolism following surgery was 1.2-1.3 per thousand.

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.

Pharmacologic profile of a low molecular weight heparin (enoxaparin): experimental and clinical validation of the prophylactic antithrombotic effects.

Some 10 low molecular weight heparin products are currently available for commercial use. Enoxaparin and fraxiparin appear to be the most developed low molecular weight heparins. Many well-designed clinical trials have been carried out for different clinical indications with both of these products. As shown in both experimental and clinical settings, the prophylactic antithrombotic efficacy of enoxaparin is distinct from other low molecular weight heparins. Enoxaparin has provided consistently impressive clinical results. Moreover, at comparable dosages, other products have exhibited safety/efficacy profiles different from that of enoxaparin. The clinical performance of each low molecular weight heparin is characteristic of only that particular agent. Besides the commercially available low molecular weight heparin preparations, some 14 other agents are under development at this time. Although each product has similar basic characteristics, their biological actions should be studied carefully. Apart from differences in the physicochemical properties, the pharmacologic actions of these agents may differ significantly. Only results from valid clinical trials will show similarities or differences between the low molecular weight heparins. Other manufacturers should follow the lead of enoxaparin and conduct their own clinical trials on each of their products.

[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.

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.

[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.

Prospective controlled vagotomy trial for duodenal ulcer. Results after 11-15 years.

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 after operation, 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 postvagotomy symptoms. The recurrent ulcer rates were 28.5% for TV, 37.4% for SV, and 39.3% for PCV. These differences were not statistically significant. The incidence of severe postvagotomy symptoms was as follows: dyspepsia, 18.4% for TV, 20.5% for SV, 8.6% for PCV; dumping, 5.9% for TV, 19.6% for SV, 2.2% for PCV; diarrhea, 9.8% for TV, 11.8% for SV, 4.4% for PCV. The incidence of severe dumping was significantly less frequent among the PCV patients than the SV group. The differences did not reach statistical significance in any of the other groups. 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. It is concluded that none of the three forms of vagotomy can be recommended as the standard operative treatment of duodenal ulceration.