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Biomedical subjects

Alexander G G Turpie

Publications and source records attributed to Alexander G G Turpie.

At least 19 recordsLinked to original sources
PubMed2003

Perioperative management of patients receiving oral anticoagulants: a systematic review.

BACKGROUND: The safety and efficacy of various management strategies for patients receiving oral anticoagulants (OACs) who need to undergo surgery or invasive procedures are unknown. METHODS: We performed a systematic review and synthesis of the English-language literature examining the perioperative management and outcomes of patients receiving long-term OAC therapy. RESULTS: Thirty-one reports were identified. The quality of the identified reports was generally poor; no randomized controlled trials have been performed and duration of follow-up was typically not stated. Overall, 29 thromboembolic events occurred amont 1868 patients (1.6%; 95% confidence interval, 1.0%-2.1%), including 7 strokes (0.4%; 95% confidence interval, 0%-0.7%). Thromboembolic event rates by management strategy were 0.4% (1 of 237) for continuation of OAC, 0.6% (6 of 996) for discontinuation of OAC therapy without administration of intravenous heparin, 0% (0 of 166) for discontinuation of OAC therapy with administration of intravenous heparin, 0.6% (1 of 180) for discontinuation of OAC therapy with administration of low-molecular-weight heparin, and 8.0% (21 of 263) for unspecified or unclear strategies. Major bleeding while receiving therapeutic OAC was rare for dental procedures (0.2% [4 of 2014]), arthrocentesis (0% [0 of 32]), cataract surgery (0% [0 of 203]), and upper endoscopy or colonoscopy with or without biopsy (0% [0 of 111]). CONCLUSIONS: Most patients can undergo dental procedures, arthrocentesis, cataract surgery, and diagnostic endoscopy without alteration of their regimen. For other invasive and surgical procedures, oral anticoagulation needs to be withheld, and the decision whether to pursue an aggressive strategy of perioperative administration of intravenous heparin or subcutaneous low-molecular-weight heparin should be individualized. The current literature is substantially limited in its ability to help choose an optimal strategy. Further and more rigorous studies are needed to better inform this decision.

Administration, Oral↗
PubMed2003

Prevention of venous thromboembolism in medical patients with enoxaparin: a subgroup analysis of the MEDENOX study.

The Medical Patients with Enoxaparin (MEDENOX) trial was a randomized, placebo-controlled study that defined the risk of venous thromboembolism (VTE) in acutely ill, immobilized, general medical patients and the efficacy of the low-molecular-weight heparin, enoxaparin, in preventing thrombosis. We performed a post-hoc analysis to evaluate the effect of 40 mg enoxaparin once daily on MEDENOX patient outcome in different types of acute medical illness (heart failure, respiratory failure, infection, rheumatic disorder and inflammatory bowel disease) and pre-defined risk factors (chronic heart and chronic respiratory failure, age, immobility, previous VTE and cancer). The primary outcome was the occurrence of documented VTE between days 1 and 14. The relative risk reduction [95% confidence intervals (CI)] for VTE comparing 40 mg enoxaparin with placebo in the subgroups were: acute heart failure, 0.29 (95% CI, 0.10-0.84); acute respiratory failure, 0.25 (95% CI, 0.10-0.65); acute infectious disease, 0.28 (95% CI, 0.09-0.81); and acute rheumatic disorder, 0.48 (95% CI, 0.11-2.16). The relative risk reduction for VTE in the pre-defined risk factor subgroups were: chronic heart failure, 0.26 (95% CI, 0.08-0.92); chronic respiratory failure, 0.26 (95% CI, 0.10-0.68); age, 0.22 (95% CI, 0.09-0.51); immobility, 0.53 (95% CI, 0.14-1.72); previous VTE, 0.49 (95% CI, 0.15-1.68); and cancer, 0.50 (95%o CI, 0.14-1.72). The beneficial effects of enoxaparin extend to a wide range of acutely ill medical patients.

Aged↗
PubMed2003

Fondaparinux, the first selective factor Xa inhibitor.

Fondaparinux (Arixtra, Sanofi-Synthelabo, Paris, France) is a pentasaccharide that selectively inhibits factor Xa; it is the first of a new class of synthetic antithrombotic agents. Fondaparinux has a linear pharmacokinetic profile allowing once-daily subcutaneous administration. Absence of metabolism, complete bioavailability, and lack of nonspecific binding in plasma contribute to the predictability of its effect. Fondaparinux has been approved for use in the prophylaxis of venous thromboembolism following orthopedic surgery. In this setting, it was found to reduce VTE risk by more than 50% in comparison with the low molecular weight heparin enoxaparin, with an incidence of clinically important bleeding not significantly different from that of standard low molecular weight heparin regimens. Furthermore, 4 weeks of prophylaxis with fondaparinux after hip fracture surgery was shown to reduce the risk of venous thromboembolism by 96% compared with 1-week prophylaxis. Finally, the efficacy and safety of fondaparinux in the treatment of venous thromboembolism and acute coronary syndromes appears promising.

Acute Disease↗
PubMed2002

Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies.

BACKGROUND: Orthopedic surgery remains a condition at high risk of venous thromboembolism (VTE). Fondaparinux, the first of a new class of synthetic selective factor Xa inhibitors, may further reduce this risk compared with currently available thromboprophylactic treatments. METHODS: A meta-analysis of 4 multicenter, randomized, double-blind trials in patients undergoing elective hip replacement, elective major knee surgery, and surgery for hip fracture (N = 7344) was performed to determine whether a subcutaneous 2.5-mg, once-daily regimen of fondaparinux sodium starting 6 hours after surgery was more effective and as safe as approved enoxaparin regimens in preventing VTE. The primary efficacy outcome was VTE up to day 11, defined as deep vein thrombosis detected by mandatory bilateral venography or documented symptomatic deep vein thrombosis or pulmonary embolism. The primary safety outcome was major bleeding. RESULTS: Fondaparinux significantly reduced the incidence of VTE by day 11 (182 [6.8%] of 2682 patients) compared with enoxaparin (371 [13.7%] of 2703 patients), with a common odds reduction of 55.2% (95% confidence interval, 45.8% to 63.1%; P<.001); this beneficial effect was consistent across all types of surgery and all subgroups. Although major bleeding occurred more frequently in the fondaparinux-treated group (P =.008), the incidence of clinically relevant bleeding (leading to death or reoperation or occurring in a critical organ) did not differ between groups. CONCLUSION: In patients undergoing orthopedic surgery, 2.5 mg of fondaparinux sodium once daily, starting 6 hours postoperatively, showed a major benefit over enoxaparin, achieving an overall risk reduction of VTE greater than 50% without increasing the risk of clinically relevant bleeding.

Aged↗
PubMed2002

Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial.

BACKGROUND: Elective hip-replacement surgery carries significant risk of venous thromboembolism, despite use of thromboprophylaxis. We aimed to see whether the pentasaccharide fondaparinux, the first drug of a new class of synthetic antithrombotic agents, could reduce this risk to a greater extent than other available treatments. METHODS: In a double-blind study, we randomly assigned 2275 consecutive patients aged 18 years or older who were undergoing elective hip-replacement surgery to receive postoperative subcutaneous injections of either 2.5 mg fondaparinux once daily or 30 mg enoxaparin twice daily. The primary efficacy outcome was venous thromboembolism to day 11. The main safety outcomes were bleeding and death. Patients were followed up for 6 weeks. FINDINGS: We assessed venous thromboembolism to day 11 in 1584 (70%) of 2275 patients. By day 11, venous thromboembolisms were recorded in 48 (6%) of 787 patients on fondaparinux and in 66 (8%) of 797 patients on enoxaparin. The relative reduction in risk was 26.3% (95% CI -10.8 to 52.8, p=0.099). The two groups did not differ in the number of patients who died or in the number who had clinically relevant bleeding. INTERPRETATION: In patients undergoing elective hip-replacement surgery, 2.5 mg fondaparinux once daily was not significantly more effective than 30 mg enoxaparin twice daily in reducing risk of venous thromboembolism. However, the lower risk recorded with fondaparinux than enoxaparin was clinically important, with no increase in clinically relevant bleeding.

Adult↗
PubMed2002

Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison.

BACKGROUND: Despite use of thromboprophylaxis, elective hip-replacement surgery carries a high risk of venous thromboembolic complications. We aimed to assess the ability of the pentasaccharide fondaparinux, the first of a new class of synthetic antithrombotic agents, to further reduce this risk. METHODS: In a double-blind study, we randomly assigned 2309 consecutive patients aged 18 years or older who were undergoing elective hip-replacement surgery to once daily, subcutaneous injections of either 2.5 mg fondaparinux, starting postoperatively, or 40 mg enoxaparin, starting preoperatively. The primary efficacy outcome was venous thromboembolism up to day 11, defined as deep-vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep-vein thrombosis, or documented symptomatic pulmonary embolism. The main safety outcomes were bleeding and death. The duration of follow-up was 6 weeks. Analysis was per protocol. FINDINGS: We assessed the primary efficacy outcome in 1827 (79%) of 2309 patients. By day 11, venous thromboembolisms were recorded in 37 (4%) of 908 patients assigned to fondaparinux and in 85 (9%) of 919 assigned to enoxaparin (difference -5.2% [95% CI -8.1 to -2.7], p<0.0001). The relative reduction in risk was 55.9% (95% CI 33.1-72.8). The two groups did not differ in frequency of death or clinically relevant bleeding. INTERPRETATION: Drugs that act through specific inhibition of factor Xa, such as fondaparinux, could be more effective than low molecular weight heparins in prevention of venous thromboembolism in patients undergoing hip-replacement surgery.

Adult↗
PubMed2002

Pentasaccharides.

Fondaparinux sodium is the first in a new class of antithrombotic agents possessing selective inhibitory activity against factor Xa. The agent was designed and developed with the objective of overcoming the limitations of currently available therapies for the prevention and treatment of venous and arterial thromboembolic disease. Extensive data from preclinical and clinical trials demonstrate fondaparinux's favorable pharmacokinetic profile combined with promising efficacy and safety results in the prevention of venous thromboembolism following major orthopedic surgery, in the treatment of deep venous thrombosis, and in acute coronary syndromes.

Animals↗
PubMed2002

Optimizing prophylaxis of venous thromboembolism.

Thrombotic events contribute significantly to the morbidity, mortality, and health care costs of patients undergoing major orthopedic surgery. Despite therapy with unfractionated heparin, low-molecular-weight heparin, or warfarin, thrombotic events continue to occur at an unacceptably high rate in populations at risk. The need for improved prophylaxis against venous thromboembolism has resulted in the development of several new antithrombotics, both recently approved and investigational, that target specific steps in the hemostatic pathway. These include direct thrombin inhibitors, agents that inhibit the factor VIIa-tissue factor complex, and selective factor Xa inhibitors. Fondaparinux is the first of the selective factor Xa inhibitors. It was evaluated in the most comprehensive drug development program ever in major orthopedic surgery, culminating in four phase III trials involving more than 7000 enrollees, and is the first agent in its class to be approved by the U.S. Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products. It has been suggested that fondaparinux's superior efficacy may be related to its ability to initiate selective inhibition of factor Xa and its predictable linear pharmacokinetics.

Arthroplasty, Replacement↗
PubMed2002

State of the art--a journey through the world of antithrombotic therapy.

The introduction of low-molecular-weight heparins (LMWHs) has contributed to major improvements in the management of venous thromboembolism (VTE). The LMWHs have been shown to be as effective as, and safer than, unfractionated heparin (UFH) in the prevention and treatment of VTE, and their use is included as a grade 1A recommendation in the Sixth American College of Chest Physicians Guidelines. Important practical disadvantages of treatment with UFH are the need for extended hospital stays and frequent monitoring of coagulation levels. In comparison, LMWHs offer convenient and cost-effective prophylaxis and treatment of VTE on an outpatient basis. The LMWHs have also had a major impact on the management of arterial thromboembolism. In patients with acute coronary syndromes (unstable angina and non-ST-segment elevation myocardial infarction), enoxaparin has demonstrated sustained clinical improvements in major ischemic outcomes compared with UFH. Antiplatelet agents have also contributed significantly to the development of effective antithrombotic therapy. Aspirin is the best known antiplatelet agent and has heretofore been the mainstay of antiplatelet therapy in unstable angina. New data indicate that combination therapy with aspirin and a novel thienopyridine, clopidogrel, may further improve outcomes in this indication.

Ambulatory Care↗
PubMed2002

Factor Xa inhibition in the prevention of venous thromboembolism and treatment of patients with venous thromboembolism.

Venous thromboembolism (VTE) is a life-threatening complication following orthopedic surgery. Selective factor Xa inhibition is a new antithrombotic approach designed to avoid difficulties associated with heparins and other current anticoagulants. Several antifactor Xa compounds are in early investigation, but fondaparinux (Arixtra; NV Organon, Oss, The Netherlands; Sanofi-Synthelabo, Paris, France) is the first and most advanced compound in the development of a new class of synthetic antithrombotic agents--the selective factor Xa inhibitors. Fondaparinux has a highly favorable pharmacokinetic profile; four large phase 3 trials comparing subcutaneous fondaparinux 2.5 mg once daily with the low molecular weight heparin (LMWH) enoxaparin in doses approved by regulatory bodies showed that fondaparinux reduced the overall risk of VTE in major orthopedic surgery by > 50% without increasing clinically relevant bleeding. Fondaparinux also appears to be a very promising candidate for the treatment of patients with existing VTE.

Animals↗
PubMed2002

Review of enoxaparin and its clinical applications in venous and arterial thromboembolism.

Venous and arterial thromboembolic disorders are common medical conditions that are associated with considerable morbidity and mortality. Unfractionated heparin (UFH) and its derivatives, the low molecular weight heparins (LMWHs), are the anticoagulants of choice when a rapid anticoagulant effect is required. LMWHs have several advantages over UFH, including a longer plasma half-life and higher bioavailability; a predictable dose response, which enables once- or twice-daily dosing; and a more convenient route of administration (subcutaneous instead of intravenous), which enables patients to self-inject in an out-patient setting. Enoxaparin is a LMWH prepared by alkaline hydrolysis of the benzylin ester of UFH. The efficacy of enoxaparin in the management of venous and arterial thromboembolism has been shown in a wide range of patient groups using doses ranging from fixed doses of 20 - 60 mg o.d. and 0.75 - 1.5 mg/kg b.i.d. Other doses, such as 80 mg/day for pregnant women with combined thrombophilic defects, have also been studied. The use of subcutaneous enoxaparin as an effective and safe home treatment for patients with acute proximal deep vein thrombosis (DVT) has been demonstrated. The benefits of preventing venous thromboembolic events with enoxaparin include reducing the costs associated with investigating the symptoms of DVT, acute treatment and hospitalisation, and potentially the development of post-thrombotic syndrome, while improving quality of life and so making the treatment cost effective. In contrast to other LMWHs, enoxaparin has been shown to provide better outcomes than UFH in the treatment of unstable angina and non-ST-segment elevation myocardial infarction, without increasing major bleeding. Adverse events with enoxaparin are infrequent; the most common events are minor bleeding complications. It should be noted that different doses or indications are approved in each country.

Anticoagulants↗
PubMed2002

Use of selective factor Xa inhibitors in special populations.

Many clinicians recommend long-term, postoperative thromboprophylaxis for patients who undergo major hip or knee replacement or hip fracture surgery. However, special care must be taken when administering pharmacoprophylaxis to such patients, as they commonly exhibit characteristics that are different from those of the general population and can affect their responses to certain drugs. Among the currently available thromboprophylactic agents are warfarin, the heparins, and the recently introduced selective factor Xa inhibitor, fondaparinux. One feature of fondaparinux is that it can be administered safely and efficaciously in a wide variety of patient populations, without the need for dosage modification.

Adult↗