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Biomedical subjects

Martin O'Donnell

Publications and source records attributed to Martin O'Donnell.

12 recordsLinked to original sources
PubMed2006

ESPRIT trial.

Explore the source record for details and available documents.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Perioperative management of oral anticoagulation.

Based on an individual assessment of risk factors for arterial or venous thrombosis and the risk of postoperative bleeding, this article outlines the preoperative and postoperative approach to anticoagulant management. Preceding this is a brief description of the therapies most commonly used in the perioperative period. The prevention of arterial thromboembolism is considered separately from the prevention of venous thrombosis.

Administration, Oral↗
PubMed2006

Preadmission antithrombotic treatment and stroke severity in patients with atrial fibrillation and acute ischaemic stroke: an observational study.

BACKGROUND: Vitamin K antagonists (eg, warfarin) substantially reduce the risk of ischaemic stroke in patients with atrial fibrillation. Additionally, therapeutic anticoagulation at time of acute stroke admission might reduce in-hospital mortality and disability. We assessed the association between preadmission antithrombotic treatment and initial stroke severity, neurological deterioration, major vascular events during hospital stay, and death or disability at discharge in patients with acute ischaemic stroke and atrial fibrillation. METHODS: We identified consecutive patients with acute ischaemic stroke and atrial fibrillation, admitted to 11 hospitals in Ontario, Canada, from the Registry of the Canadian Stroke Network (2003-05). Logistic regression was used to assess the association between antiplatelet treatment, subtherapeutic warfarin treatment (admission international normalised ratio [INR] < 2), therapeutic warfarin treatment (admission INR > or = 2), and clinical outcome. Stroke severity was measured using the Canadian neurological scale (CNS) and was categorised into mild (CNS > 7) and severe stroke (CNS < or = 7). Disability was measured with the modified-Rankin scale (mRS) and was categorised into strokes associated with no or mild-moderate dependency (mRS 0-3) and with severe dependency or death (mRS 4-6). RESULTS: Of 948 patients, 306 (32%) were not on antithrombotic treatment, 292 (31%) were receiving antiplatelet treatment, 238 (25%) were receiving warfarin with a subtherapeutic INR, and 112 (12%) were receiving warfarin with a therapeutic INR on admission. Compared with those not receiving antithrombotic therapy, antiplatelet therapy (odds ratio 0.7; 95% CI 0.5-0.995) and therapeutic warfarin (0.4; 0.2-0.6) were associated with a reduction in severe stroke at admission. Therapeutic warfarin was also associated with a reduction in the odds of severe disability or death at discharge (0.5; 0.3-0.9). INTERPRETATION: Therapeutic warfarin is associated with reduced severity of ischaemic stroke at presentation and reduced disability or death at discharge in patients with atrial fibrillation. Antiplatelet treatment is associated with a more modest reduction than warfarin in baseline stroke severity.

Aged↗
PubMed2004

New anticoagulants.

Anticoagulants are pivotal agents for prevention and treatment of thromboembolic disorders. Limitations of existing anticoagulants, vitamin K antagonist and heparins, have led to the development of newer anticoagulant therapies. These anticoagulants have been designed to target specific coagulation enzymes or steps in the coagulation pathway. New anticoagulants that are under evaluation in clinical trials include: (1) inhibitors of the factor VIIa/tissue factor pathway; (2) factor Xa inhibitors, both indirect and direct; (3) activated protein C and soluble thrombomodulin; and (4) direct thrombin inhibitors. Although most of these are parenteral agents, several of the direct inhibitors of factor Xa and thrombin are orally active. Clinical development of these therapies often starts with studies in the prevention of venous thrombosis before evaluation for other indications, such as prevention of cardioembolism in patients with atrial fibrillation or prosthetic heart valves. At present, the greatest clinical need is for an oral anticoagulant to replace warfarin for long-term prevention and treatment of patients with venous and arterial thrombosis. Ximelagatran, an oral direct thrombin inhibitor, is the first of a series of promising new agents that might fulfill this need. Large phase 3 trials evaluating ximelagatran for the secondary prevention of venous thromboembolism and prevention of cardioembolic events in patients with atrial fibrillation have been completed.

Anticoagulants↗
PubMed2004

Methodology for guideline development for the Seventh American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.

This article describes the methodology for the Seventh American College of Chest Physicians (ACCP) Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines. Guideline authors began by specifying the population, the intervention and alternative, and the outcomes for each clinical question, and defined the criteria for eligible articles, including methodological criteria, for each recommendation. Librarians, in collaboration with guideline authors and methodologists, conducted systematic searches for evidence. Guideline authors systematically evaluated the evidence, considered the full range of benefits, risks, inconvenience, and costs associated with alternative management strategies, considered patients' underlying values and preferences, and made recommendations accordingly. To increase the likelihood that the recommendations adequately represent patient values and preferences, the development process included a review of recommendations by research methodologists, practicing generalists, and specialists. Chapters are organized so that evidence is clearly linked to the relevant recommendations, and that recommendations particularly sensitive to underlying values and preferences are explicitly identified. Authors paid careful attention to the strength of the underlying evidence and to the balance between risks and benefits, which are both reflected in the grades of recommendations. Thus, improvements to the process of making recommendations for the ACCP guidelines include the explicit definition of questions, transparent eligibility criteria for including studies, and the specification of values and preferences underlying recommendations where they are particularly relevant. In combination with our previous practice of grading recommendations according to their strength, and the methodological quality of the supporting studies, these innovations establish our guidelines as, by and large, evidence based.

Bias↗
PubMed2004

Novel antithrombotic therapies for the prevention of stroke in patients with atrial fibrillation.

Atrial fibrillation (AF), the most common type of arrhythmia in adults, is a major risk factor for stroke. The prevalence of AF increases with age, occurring in 1% of persons <60 years of age and in almost 10% of those >80 years of age. Recent studies show that treatment strategies that combine control of ventricular rate with antithrombotic therapy are as effective as strategies aimed at restoring sinus rhythm. Current antithrombotic therapy regimens in patients with AF involve chronic anticoagulation with dose-adjusted vitamin K antagonists unless patients have a contraindication to these agents or are at low risk for stroke. Patients with AF at low risk for stroke may benefit from aspirin. Although vitamin K antagonists are effective, their use is problematic, highlighting the need for new antithrombotic strategies. This article will (a) provide an overview of the clinical trials that form the basis for current antithrombotic guidelines in patients with AF, (b) highlight the limitations of current antithrombotic drugs used for stroke prevention, (c) briefly review the pharmacology of new antithrombotic drugs under evaluation in AF, (d) describe ongoing trials with new antiplatelet therapies and idraparinux, and completed studies with ximelagatran in patients with AF, and (e) provide clinical perspective into the potential role of new antithrombotic drugs in AF.

Adult↗
PubMed2003

Reduction of out-of-hospital symptomatic venous thromboembolism by extended thromboprophylaxis with low-molecular-weight heparin following elective hip arthroplasty: a systematic review.

BACKGROUND: Numerous trials and meta-analyses have shown that extended out-of-hospital prophylaxis with low-molecular-weight heparin reduces asymptomatic and symptomatic venous thromboembolism after total hip arthroplasty. We hypothesized that knowledge of the results of screening tests may have resulted in overdiagnosis of symptomatic venous thromboembolism in many of these studies. The purpose of this analysis was to obtain an accurate estimate of the absolute risk reduction (ARR) of symptomatic venous thromboembolism after discharge from hospital in controlled studies that avoided this potential bias for overdiagnosis. METHODS: Articles were identified using MEDLINE, EMBASE, and the Cochrane Library databases (January 1980-April 2002). Studies were eligible if the assessment of symptomatic venous thromboembolism was standardized and performed independently of mandatory objective testing. RESULTS: Two studies (907 patients) were eligible for assessment of symptomatic venous thromboembolism, 5 studies (1917 patients) for symptomatic pulmonary embolism, and 7 studies (2425 patients) for fatal pulmonary embolism. In controls vs extended treatment groups, after hospital discharge, the frequency of symptomatic venous thromboembolism was 2.7% vs 1.1% (ARR, 1.56%; 95% confidence interval [CI], -0.21% to 3.3%; number needed to treat, 64); symptomatic pulmonary embolism was 0.36% vs 0% (ARR, 0.36%; 95% CI, -0.3% to 1.36%; number needed to treat, 278); and fatal pulmonary embolism was 0.09% vs 0% (ARR, 0.09%; 95% CI, -0.08% to 0.27%; number needed to treat, 1093). CONCLUSIONS: The absolute reduction in symptomatic venous thromboembolism attributed to extended prophylaxis in some studies and meta-analyses seems to have been overestimated.

Arthroplasty, Replacement, Hip↗
PubMed2003

A diagnostic strategy involving a quantitative latex D-dimer assay reliably excludes deep venous thrombosis.

BACKGROUND: Because clinical diagnosis is inaccurate, objective testing is usually considered necessary when patients present with suspected deep venous thrombosis (DVT). OBJECTIVE: To determine whether a negative result on a quantitative latex D dimer assay eliminates the need for further investigation in patients with a low or moderate pretest probability of DVT. DESIGN: Prospective cohort study. SETTING: Three tertiary care hospitals in Canada. PATIENTS: 556 consecutive outpatients with suspected first DVT. INTERVENTION: Patients were categorized as having a low, moderate, or high pretest probability of DVT and then underwent D-dimer testing. Patients with low or moderate pretest probability and a negative D-dimer result had no further diagnostic testing and received no anticoagulant therapy. Serial compression ultrasonography was performed in all other patients. Patients who did not receive a diagnosis of DVT were followed for symptomatic venous thromboembolism. MEASUREMENTS: Objectively confirmed symptomatic venous thromboembolic events during 3 months of follow-up. RESULTS: 283 patients (51%) had low or moderate pretest probability and a negative D-dimer result. One of these patients had DVT during follow-up (negative likelihood ratio, 0.05 [CI, 0.01 to 0.23]). The negative likelihood ratio of the d -dimer test in all patients was 0.03 (CI, 0.01 to 0.16). CONCLUSION: A negative result on a quantitative latex d -dimer assay safely eliminates the need for further testing in patients with low or moderate pretest probability of DVT.

Fibrin Fibrinogen Degradation Products↗
PubMed2003

Thromboprophylaxis in surgical patients.

Venous thromboembolism is the most common preventable cause of death in surgical patients. Thromboprophylaxis, using mechanical methods to promote venous outflow from the legs and antithrombotic drugs, provides the most effective means of reducing morbidity and mortality in these patients. Despite the evidence supporting thromboprophylaxis, it remains underused because surgeons perceive that the risk of venous thromboembolism is not high enough to justify the potential hemorrhagic complications of anticoagulant use. The risk of venous thromboembolism is determined by patient characteristics and by the type of surgery that is performed. In this paper we identify the risk factors for venous thromboembolism and provide a scheme for stratifying surgical patients according to their risk. We describe the mechanism of action of the various forms of thromboprophylaxis and outline the evidence supporting thromboprophylaxis in different surgical settings. Finally, we recommend optimal forms of thromboprophylaxis in patients who undergo various types of surgery. Intermittent pneumatic compression, with or without elastic stockings, can be used for thromboprophylaxis in patients who undergo neurosurgical procedures; for patients who undergo vascular or cardiovascular procedures, long-term acetylsalicylic acid should be used for thromboprophylaxis. Low-molecular-weight heparin (LMWH) or warfarin is the choice for patients with spinal cord operations and all patients with major trauma who do not have contraindications to anticoagulation should receive thromboprophylaxis with LMWH.

Anticoagulants↗