Thromboembolism Prophylaxis In Patients Research Articles

Safety of heparin prophylaxis for venous thromboembolism in patients with neurotrauma

Patients with neurotrauma are at high risk for VTE. The safety of early anticoagulation for neurotrauma has not been established. Our study was based on the hypothesis that unfractionated heparin can be safely administered to most patients with neurotrauma for VTE prophylaxis.

Neurological Outcomes in Patients With Ischemic Stroke Receiving Enoxaparin or Heparin for Venous Thromboembolism Prophylaxis

The Prevention of VTE after Acute Ischemic Stroke with LMWH (PREVAIL) study demonstrated that enoxaparin was superior to unfractionated heparin (UFH) in preventing venous thromboembolism in patients with ischemic stroke and was associated with a small but statistically significant increase in extracranial hemorrhage rates. In this PREVAIL subanalysis, we evaluate the long-term neurological outcomes associated with the use of enoxaparin compared with UFH. We also determine predictors of stroke progression. Acute ischemic stroke patients aged >or=18 years, who could not walk unassisted, were randomized to receive enoxaparin (40 mg once daily) or UFH (5000 U every 12 hours) for 10 days. Patients were stratified according to baseline stroke severity using the National Institutes of Health Stroke Scale score. End points for this analysis included stroke progression (>or=4-point increase in National Institutes of Health Stroke Scale score), neurological outcomes up to 3 months postrandomization (assessed using National Institutes of Health Stroke Scale score and modified Rankin Scale score), and incidence of intracranial hemorrhage. Stroke progression occurred in 45 of 877 (5.1%) patients in the enoxaparin group and 42 of 872 (4.8%) of those receiving UFH. Similar improvements in National Institutes of Health Stroke Scale and modified Rankin Scale scores were observed in both groups over the 90-day follow-up period. Incidence of intracranial hemorrhage was comparable between groups (20 of 877 [2.3%] and 22 of 872 [2.5%] in enoxaparin and UFH groups, respectively). Baseline National Institutes of Health Stroke Scale score, hyperlipidemia, and Hispanic ethnicity were independent predictors of stroke progression. The clinical benefits associated with use of enoxaparin for venous thromboembolism prophylaxis in patients with acute ischemic stroke are not associated with poorer long-term neurological outcomes or increased rates of symptomatic intracranial hemorrhage compared with UFH.

Pharmacology, Pharmacokinetics, and Pharmacodynamics of Dabigatran Etexilate, an Oral Direct Thrombin Inhibitor

Dabigatran etexilate is a novel, oral reversible direct thrombin inhibitor that is rapidly absorbed and converted to its active form, dabigatran. Dabigatran has been shown to be a potent, competitive, and reversible inhibitor of thrombin, inhibiting both thrombin activity and generation. Studies in healthy volunteers and in patients undergoing orthopedic surgery indicate that dabigatran has a predictable pharmacokinetic profile, allowing for a fixed-dose regimen without the need for coagulation monitoring. In healthy volunteers, peak plasma concentrations of dabigatran are reached approximately 2 hours after oral administration. The elimination half-life is 12 to 14 hours, with clearance predominantly occurring via renal excretion of unchanged drug. Dabigatran is not metabolized by cytochrome P450 isoenzymes, has no interactions with food, and also has a low potential for drug-drug interactions. The pharmacokinetic profile of dabigatran is consistent across a broad range of different patient populations and is unaffected by gender, body weight, ethnic origin, obesity, and mild-to-moderate hepatic impairment. Small differences in dabigatran pharmacokinetics associated with age are attributable to variation in renal function. Dabigatran etexilate produces a predictable pharmacodynamic effect and requires no coagulation monitoring. It has been approved in the European Union (EU) and Canada for prophylaxis of thromboembolism in patients undergoing total knee or hip arthroplasty. Ongoing clinical trials are investigating its use in the treatment of venous thromboembolism, prevention of stroke in patients with nonvalvular atrial fibrillation, and treatment of thromboembolic complications, following acute coronary syndromes.

Coadministration of Dabigatran Etexilate and Atorvastatin

Dabigatran etexilate, a novel oral direct thrombin inhibitor, has been approved for prophylaxis of thromboembolism in patients undergoing total knee or total hip replacement, and is under clinical investigation for treatment of venous thromboembolism, prevention of stroke in patients with atrial fibrillation, and the treatment of thromboembolic complications following acute coronary syndromes. To evaluate the potential impact of atorvastatin coadministration on the pharmacokinetics, pharmacodynamics, and safety of dabigatran etexilate. Healthy male and female volunteers (n = 22) were recruited to this open, randomized, multiple-dose, three-way crossover study. They received dabigatran etexilate 150 mg twice daily on days 1-3 and once daily on day 4, atorvastatin 80 mg once daily on days 1-4, or both treatments together on days 1-4. Exposure to dabigatran at steady state (area under the drug plasma concentration-time curve at steady state) was reduced by 18% with concomitant atorvastatin administration. An 18% increase in plasma atorvastatin concentration occurred with coadministration of dabigatran etexilate. Exposure to its metabolite 2'-hydroxy-atorvastatin remained essentially unchanged and exposure to 4'-hydroxy-atorvastatin was increased by 15%. The small changes observed are deemed of little clinical relevance given the overall inter-individual variability in the metabolism of atorvastatin. Furthermore, there were no changes in the concentrations of active HMG-CoA reductase inhibitors in plasma following dabigatran etexilate coadministration. Six subjects in the atorvastatin treatment group, six subjects during combination treatment, and eight subjects in the dabigatran treatment group reported adverse events. Most of the adverse events reported were nervous system disorders such as dizziness and headache, and general disorders such as fatigue. All adverse events were resolved at the end of the study. Results of this randomized, open-label, three-way crossover design study in healthy male and female volunteers showed that atorvastatin had no influence on the pharmacokinetic/pharmacodynamic profile of dabigatran, and vice versa, dabigatran etexilate had no impact on the pharmacokinetic/pharmacodynamic profile of atorvastatin. Both drugs were well tolerated when given alone or in combination.

Low Platelet Counts in Cancer Patients: Should Heparin for Venous Thromboembolism Prophylaxis Be Instituted?

and platelet levels of 18,000/mm 3 who developed an acute upper extremity deep vein thrombus. Although in her case, it was clearly related to a peripherally inserted central catheter in the affected limb, we wonder if it demonstrates her being at a considerably high risk for spontaneous thromboembolic events. The treating team could not gather sufficient evidence to institute prophylactic dosage of heparin in view of her high presumed risk of bleeding. Two out of the three majorrandomized,double-blind,placebo-controlledtrialsonthromboembolism prophylaxis in hospitalized patients (the Prophylaxis in Medical Patients with Enoxaparin trial and the Prevention of Recurrent Venous Thromboembolism study), have specifically excluded patients with platelet counts less than 100,000/mm 3 . 2,3 As such, evidence for thromboembolism prophylaxis in patients with platelet count less than 100,000/mm 3 is probably not clear.

Melagatran for thromboprophylaxis after mechanical valve implantation: Results in a heterotopic porcine model

Melagatran, the active form of ximelagatran, is a novel, direct thrombin inhibitor that does not have a narrow therapeutic window regarding hemorrhagic and thromboembolic events. We aimed to determine whether melagatran would be effective in preventing thrombus formation on heterotopically placed mechanical heart valves. A graft containing a bileaflet mechanical heart valve was implanted in the descending thoracic aorta of domestic swine. Two groups of 6 animals received daily subcutaneous injections of either melagatran (2.4 mg/kg, 3 times per day) or dalteparin (175 U/kg, 2 times per day) for 30 days. Four control animals received no anticoagulation therapy. Fecal HemoQuant and serum hemoglobin levels were recorded. Thirty days after the procedure, platelets were labeled with indium 111, the abdominal organs were inspected, and thrombi and platelets deposited on the valve were measured. Median thrombus burden on the valves was 0.4 mg (interquartile range, 0.15-5.45 mg) with melagatran, 0.5 mg (interquartile range, 0-14.5 mg) with dalteparin, and 168 mg (interquartile range, 32.5-665.75 mg) for controls (melagatran vs dalteparin and control; P = .04). Median platelet deposition on the valves was 0 (interquartile range, 0-8.9 x 10(4)) with melagatran, 49.9 x 10(4) (interquartile range, 27.9 x 104-191.8 x 10(4)) with dalteparin, and 115.2 x 10(4) (interquartile range, 9.6 x 10(4)-243 x 10(4)) for controls (melagatran vs dalteparin and control; P = .02). Melagatran did not increase the risk of thromboembolism or bleeding. Thrombus and platelet accumulation on the prosthetic valves was decreased by melagatran and dalteparin. The use of melagatran or other related direct thrombin inhibitors warrants further study in prophylaxis of thromboembolism in patients with mechanical heart valves.

Bleeding While Starting Anticoagulation for Thromboembolism Prophylaxis in Elderly Patients With Atrial Fibrillation

Growing old is like being increasingly penalized for a crime you haven’t committed. — —Anthony Powell, Temporary Kings Anticoagulation therapy for thromboembolism prophylaxis in patients with atrial fibrillation (AF) is based on quality information derived from numerous randomized controlled trials but continues to be a conundrum for many physicians. The AF treatment guidelines have been revised recently,1 but new information is emerging at such a rapid rate that it is hard to imagine how the guideline process can keep up with the pace. In this issue of the journal, there is new and rather startling information derived from careful observation of the initiation of warfarin therapy in a cohort of elderly patients with AF.2 Several aspects of this study deserve emphasis. Article p 2689 The subjects in the cohort of Hylek et al2 possess some unique characteristics. The obvious one is the age of the patients. All were aged ≥65 years. It is equally notable that none of them had been on warfarin during the preceding year. A substantial proportion of women were included in the cohort. Among those aged ≥80 years, 55% were women. It is also notable that the duration of follow-up was restricted to the first year of warfarin therapy. The most obvious finding to be emphasized is the high proportion of serious bleeding incidents. The reported amount of major bleeding during use of vitamin K antagonists over nearly 2 decades has varied (see Table 42). There is, however, a discernible pattern over time. In general, less major bleeding was reported in older studies than in recent studies. A pooled analysis of the original major randomized controlled trials of anticoagulation for thromboembolism prophylaxis in AF patients reported an annual rate of major hemorrhage of 1.3% in 1994.3 However, it is rare that …

Ximelagatran versus warfarin for prophylaxis of venous thromboembolism in major orthopedic surgery: systematic review of randomized controlled trials

Ximelagatran has been recently studied for prophylaxis in surgical orthopedic cases. We proposed to establish whether interventions involving ximelagatran, as compared with warfarin, would increase thromboembolic prophylaxis in patients undergoing major orthopedic knee surgery. Studies with random assignment were identified by an electronic search of the medical literature up to 2006. Data were double-entered into the Review Manager software, version 4.2.5. We included three well-conducted clinical trials involving 4,914 participants. Sub-groups with two dosages of ximelagatran (24 mg and 36 mg, b.i.d.), were defined. Ximelagatran showed significantly lower frequency of total venous thromboembolism (VTE) than warfarin, but only with the 36-mg dosage (risk relative, RR: 0.72; 95% confidence interval, CI: 0.64-0.81; p < 0.00001). For the 24-mg subgroup, total VTE frequency was similar (RR: 0.86; 95% CI: 0.73-1.01; p = 0.06). No significant differences were shown with either ximelagatran dosage for deep vein thrombosis (DVT), pulmonary embolism, any bleeding or severe bleeding. At the end of the treatment, alanine aminotransferase (ALT) elevation was less frequent in the 24-mg ximelagatran sub-group (RR: 0.33; 95% CI: 0.12-0.91; p = 0.03], but during the follow-up period, the ALT elevation rate was greater in the 36-mg ximelagatran group (RR: 6.97; 95% CI: 1.26-38.50; p = 0.03]. Ximelagatran appears to be more effective than warfarin when used in higher dosages (36 mg b.i.d.), but at the expense of increased frequency of ALT elevation during the follow-up period.

Preoperative Low Molecular Weight Heparin as Venous Thromboembolism Prophylaxis in Patients at Risk for Prosthetic Infection After Knee Arthroplasty

To investigate the effect of preoperative initiation of low molecular weight heparin as prophylaxis for deep venous thrombosis in patients at risk of developing surgical-site infections after knee arthroplasty. Case-control study nested in a cohort. The incidence of surgical-site infection in the cohort was calculated. With the use of data extracted from medical histories and after adjustment for other risk factors, the effect of preoperative heparinization on the risk of incisional and prosthetic infection among case-patients and control-patients (1:3 ratio) was assessed. Orthopedic department in a tertiary-care referral hospital. A cohort of 160 consecutive patients who had received prosthetic knee implants between October 1, 2001, and November 30, 2003. Eighteen patients with surgical-site infections were identified, yielding an incidence of incisional and prosthetic infection of 6.9 (95% confidence interval [CI95], 3.5 to 12.0) and 4.4 (CI95, 1.8 to 8.8) cases per 100 patients undergoing surgery, respectively. Surgical-site infection was associated with preoperative use of low molecular weight heparin (odds ratio [OR], 6.2 after adjustment for medical and surgical factors; CI95 1.5 to 23). Prosthetic infection was strongly associated with preoperative use of prophylaxis (OR, undetermined [100% exposure in case-patients vs 35% exposure in control-patients]; P = .002), but incisional surgical-site infection was not. The use of low molecular weight heparins immediately before knee arthroplasty as prophylaxis for deep venous thrombosis should be questioned because of probable increased risk of prosthetic infection.

Current use of thromboembolism prophylaxis for laparoscopic cholecystectomy patients in Sweden

The need for thromboembolism (TE) prophylaxis during laparoscopic surgery is not well established. The aim of this study was to investigate current TE prophylaxis in patients undergoing laparoscopic cholecystectomy (LC) in Sweden. Mail questionnaire to all Surgical Departments in Sweden about the current use of thromboembolism prophylaxis in patients undergoing laparoscopic cholecystectomy. The response rate was 78 of 80 departments of surgery (98%). Seventy reported performing LC. Thirty-six percent used thromboembolism prophylaxis in all patients, 17% in most, 9% in half their patients and 39% only rarely. The current use of thromboembolism prophylaxis ranged from low-molecular-weight heparin for 7 days + stockings in all patients to no prophylaxis at all in the majority of patients. The use of thromboembolism prophylaxis in LC patients is highly variable, even in the small and homogenous country of Sweden. Further studies concerning the risk of TE complications after laparoscopic surgery are warranted.

Direct antithrombins: new perspectives in cardiovascular medicine.

Thrombin converts fibrinogen to fibrin and is the most powerful activator of platelets thus playing a crucial role in arterial and venous thrombosis. The limitations of heparin, largely used in the therapy of arterial and venous thromboembolism, has prompted the development of new antithrombotic drugs, able to directly inhibit thrombin. They comprise hirudin, bivalirudin and argatroban, which are antithrombins for parenteral use, and the orally active ximelagatran which, once absorbed, is converted to the active compound melagatran. Hirudin is a polypeptide able to irreversibly block both the active site and the fibrin(ogen) binding site of thrombin; bivalirudin, a synthetic hirudin derivative, has the same binding sites of hirudin to thrombin but has a shorter pharmacological action and is safer for clinical use. Several clinical trials which tested these drugs in acute coronary syndromes, coronary angioplasty and venous thromboembolism. demonstrate that hirudin and bivalirudin are superior to heparin in significantly reducing cardiac major events. The advantage of hirudin and bivalirudin over heparin was also confirmed in adjuncts to thrombolytic therapy as well as in percutaneous angioplasty relating to thrombotic events but not to restenosis. Hirudin was also significantly better than both unfractionated heparin and low molecular weight heparin (LMWH) in the prophylaxis of venous thromboembolism in patients undergoing elective arthroplasty. Major bleeding associated to hirudin was not different from that observed with heparin. Preliminary data also indicate that melagatran/ximelagatran may be used in the prophylaxis of venous thromboembolism and in the prevention of arterial embolism in patients with non-valvular atrial fibrillation.

Sealing of the mediastinum with a local hemostyptic agent reduces chest tube duration after complete mediastinal lymph node dissection for stage I and II non–small cell lung carcinoma

Background We assessed the impact of coverage of the mediastinum with a local hemostyptic agent as well as the impact of perioperative thromboembolic prophylaxis on cumulative chest drain volume and on the duration of chest tubes after surgical resection with complete mediastinal lymph node dissection for stage I or II non–small cell lung cancer. Methods In a prospective, randomized two-by-two factorial design, 80 patients with clinical stage I or II non–small cell lung cancer were allocated to one of two surgical therapy arms (TachoComb or conventional surgical hemostasis) and one of two anticoagulation arms (enoxaparin 4,000 IU or dalteparin 5,000 IU). Primary end point was cumulative chest drain volume; secondary end point was duration of chest tubes. Additionally clinical data were obtained. Results Comparison of the surgical arms revealed significantly lower cumulative chest drain volumes and thereby an earlier chest tube removal in the TachoComb group ( p = 0.045). With regard to thromboembolic prophylaxis, a significantly earlier chest tube removal was found for patients treated with dalteparin ( p = 0.039). Analysis of the interaction of surgical and anticoagulation treatment revealed the combined use of TachoComb and dalteparin was superior to other combinations (cumulative chest drain volumes 498 ± 67 mL versus 1,000 ± 88 mL, 924 ± 87 mL, and 895 ± 118 mL; p = 0.008; mean duration of chest tubes 1.78 ± 0.15 days versus 2.96 ± 0.21 days, 2.93 ± 0.17 days, and 3.06 ± 0.27 days; p = 0.019). Conclusions The combined use of a local hemostyptic agent and dalteparin seems superior as compared with other regimens of hemostasis and thromboembolic prophylaxis in patients undergoing surgical resection and complete mediastinal lymph node dissection for stage I and II non–small cell lung cancer with regard to cumulative chest drain volume as well as duration of chest tubes.

Clinical Experience with Ximelagatran in Orthopaedic Surgery

Patients who undergo orthopaedic surgery are at substantially increased risk for venous thromboembolic events. These include proximal and distal deep vein thrombosis, with the former more likely to lead to pulmonary embolism and fatal complications. Anticoagulants are routinely used for venous thromboembolism prophylaxis in patients undergoing total hip or total knee replacement surgery. Although current treatments offer effective prophylaxis, they have disadvantages. Warfarin is limited by the requirement for coagulation monitoring to ensure effective and safe use. Similarly, low-molecular-weight heparins (LMWHs) have disadvantages, including the need for parenteral administration. This article brings together data from clinical trials of the novel oral direct thrombin inhibitor, ximelagatran, in the prevention of venous thromboembolism in patients undergoing elective total hip or total knee replacement. The ximelagatran clinical trial programme in orthopaedic surgery has focused primarily on five large multicentre studies in Europe (the Melagatran Thromboprophylaxis in Orthopaedic surgery II and III and Expanded Prophylaxis Evaluation Surgery Study studies) and in the United States (the Exanta Used to Lessen Thrombosis A and B studies), which enrolled more than 8000 patients. In addition, the USA clinical trial programme included three other trials that investigated ximelagatran in orthopaedic surgery; two of these studies focused on prevention of venous thromboembolism after total knee replacement, and one study investigated prevention of venous thromboembolism after total hip replacement. These studies compared ximelagatran with the LMWHs dalteparin and enoxaparin and with warfarin, and were designed to reflect regional differences in venous thromboembolism prophylaxis and to build on findings from previous studies. Generally, ximelagatran has been shown to possess comparable or greater efficacy relative to comparators. The timing and dose of ximelagatran have been shown to be important determinants of its efficacy and safety. As ximelagatran can be given in fixed oral dosing without coagulation monitoring, it is an attractive choice for the prevention of venous thromboembolism in major elective orthopaedic surgery.

Modifications of coagulation and fibrinolytic parameters in laparoscopic cholecystectomy.

The incidence of deep vein thrombosis and pulmonary embolism following laparoscopic surgery is unknown and studies on alterations of hemostasis after laparoscopy are inconclusive. In this study we prospectively evaluated changes in prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen (Fg), antithrombin III (ATIII), prothrombin fragment F 1 + 2, beta-thromboglobulin (betaTG) and D-dimer (D-D), preoperatively and 24 h after laparoscopic surgery in 16 patients. Comparing pre- and postoperative values, no statistical differences were observed in aPTT, F1 + 2, and ATIII measurements. Postoperative PT values increased slightly (p approximately 0.05) after surgery. Conversely, Fg, betaTG, and D-D values were statistically higher in the 24-h evaluation (p = 0.008, 0.01, and 0.045, respectively). These data suggest that laparoscopic surgery induces activation of coagulation and fibrinolytic pathways and, additionaly, betaTG elevation, which has never been reported and might account for postoperative platelet activation and a greater risk of thrombogenicity. Therefore, routine thromboembolic prophylaxis in patients undergoing laparoscopic surgery is recommended.

Tinzaparin.

Low-molecular-weight heparins (LMWH) are efficacious agents that offer clinical and pharmacoeconomic advantages over unfractionated heparin (UFH) for the treatment of ACS and venous thromboembolism. Tinzaparin is a LMWH approved for the treatment of deep venous thrombosis with and without pulmonary embolism, when used in conjunction with warfarin. In studies with hospitalized patients who had deep venous thrombosis or pulmonary embolism, tinzaparin was at least as efficacious as UFH, with fewer adverse bleeding events. It is also efficacious for thromboembolic prophylaxis in patients undergoing general and orthopedic surgery. Studies have shown that tinzaparin is at least as effective as UFH for patients undergoing surgery and in other patients at risk for developing thromboembolism. It is currently not recommended for use in patients with ischemic strokes. There are minimal data available regarding its use in the management of patients with unstable angina (UA) and non-ST-segment elevation myocardial infarction.

Cost/death averted with venous thromboembolism prophylaxis in patients undergoing total knee replacement or knee arthroplasty.

To compare the cost-effectiveness of warfarin or enoxaparin with no prophylaxis for prevention of venous thromboembolism in patients undergoing total knee replacement (TKR) or knee arthroplasty. Literature search and retrospective database analysis. Cohort of 42,692 patients over 40 years old who underwent TKR or knee arthroplasty, with a subsequent length of stay of at least 1 day, and who did not die postoperatively. Both warfarin and enoxaparin were superior to no prophylaxis with regard to costs and clinical outcomes. Enoxaparin was associated with medical charges of $26,455/patient and prevented 194 deaths/10,000 patients. Warfarin was associated with medical charges of $27,360/patient and prevented 124 deaths/10,000 patients. A wide range of model estimates and assumptions identify enoxaparin as the prophylaxis modality of choice for preventing venous thromboembolism and subsequent clinical complications following total knee replacement surgery.

Thromboembolic prophylaxis: practice in oral and maxillofacial surgery

Describes how the implementation of thromboembolic prophylaxis in patients undergoing oral and maxillofacial surgical procedures was audited. In 1997, four oral and maxillofacial units were asked about their practice of prophylaxis for thromboembolic disease (TED). Proformas were sent to each unit to assess 45 patients retrospectively. These patients were chosen at random from within defined groups of surgery. The audit was repeated in 1998, after presentation and discussion of initial findings. Of 117 patients at low risk of TED, 72 (62 per cent) and 50 (81 per cent) of 62 patients at moderate risk received prophylaxis. In the second run of the audit, there was a 7 per cent increase in the number of patients at moderate risk receiving prophylaxis. Patients admitted for trauma surgery were the most likely to have TED prophylaxis omitted. Concludes that there was an improvement between the first and second run of the audit, but some patients were still not being treated appropriately.

Prophylaxis of thromboembolism in spinal injuries—survey of practice in spinal units in the British Isles

Aim: Survey and discussion of the current thromboembolic prophylaxis practice in spinal injury units within the British Isles. Background: Deep vein thrombosis and pulmonary embolism are major causes of morbidity and mortality in patients with spinal injuries. A wide range of thromboprophylactic measures have been proposed. The optimum treatment and duration for thromboprophylaxis in spinal injuries is unknown. Different spinal units within the British Isles use different measures despite similar training backgrounds. The present study was performed to review practice and make suggestions on best practice using literature review. Methods: All the 13 regional and national spinal injury referral centres within the British Isles were contacted to find out their protocols for thromboembolic prophylaxis in patients with acute spinal injuries. Results: All units replied. A wide variation in methods used was found in different spinal units ranging from no chemical prophylaxis to oral anticoagulation with warfarin and contrasting views on the use of antithromboembolic stockings. Conclusion: All units recognised the risk of thromboembolism after spinal injuries. A wide variety of thromboprophylactic measures are used.

Management of atrial fibrillation: discrepancy between guideline recommendations and actual practice exposes patients to risk for complications.

To assess compliance to guidelines in the management of patients with atrial fibrillation. A total of 728 questionnaires were mailed to physicians with the intention of studying 'theoretical' compliance to practice guidelines. A retrospective evaluation of 200 records from consecutive patients hospitalized with atrial fibrillation was performed in order to verify 'actual' compliance to guidelines. The response rate to the questionnaires was 68%. More than 94% of the physicians stated that patients with risk factors for thromboembolic complications and chronic atrial fibrillation should receive long-term warfarin treatment. Of evaluated records, 108 patients were in chronic atrial fibrillation with at least one risk factor for stroke, and with no known contraindication to warfarin. In this group, only 40% received warfarin. Moreover, several other discrepancies were detected as regards the use of antiarrhythmic therapy. This study reveals a clear discrepancy between recommendations in guidelines and actual practice in patients with atrial fibrillation. The most important finding was a significant under use of thromboembolic prophylaxis in patients at high risk for such events. Implementation and the study of adherence to management guidelines on atrial fibrillation need to be carefully reviewed by surveys of actual clinical practice in order to establish reasonable therapeutic quality.

Economic evaluation of the use of nadroparin calcium in the prophylaxis of deep vein thrombosis and pulmonary embolism in surgical patients in Italy.

The objective of this study was to compare the costs, from the perspective of the payer, of using nadroparin calcium, a low-molecular-weight heparin, instead of unfractionated heparin in the prophylaxis of venous thromboembolism in patients undergoing orthopaedic surgery or major general surgery in Italy. The methods used were based on a published meta-analysis and a survey of clinical practice. We constructed a model of the prophylaxis and management of venous thromboembolism in Italy. Resource use associated with individual events was estimated on the basis of the clinical survey. Unit costs, not available from published sources, were taken from charges made by hospitals and from direct observation. A sensitivity analysis was conducted to examine whether the results were robust to changes in key variables. In the base case, compared with unfractionated heparin, prophylaxis with nadroparin calcium reduced the expected costs of managing thromboembolism by 267,226 Italian lire (L, 1994 values; $US1 = L1600 approx.) per patient undergoing orthopaedic surgery, and by L45,588 per patient undergoing major general surgery. Therefore, switching from unfractionated heparin to nadroparin calcium in these patients offers the possibility of significant cost savings to the Italian healthcare system.