01 Jan 10

Perioperative use of anti-platelet drugs

Posted in Anesthesia, Anticoagulation, Coronary artery disease, Pre-operatie evaluation at 16:19 by Laci

by P Chassot, A Delabays, D Spahn

Best Pract Res Clin Anaesthesiol 2007; 21:241–256

Performing a surgical procedure on a patient undergoing anti-platelet therapy raises a dilemma: is it safer to withdraw the drugs and reduce the haemorrhagic risk, or to maintain them and reduce the risk of myocardial ischaemic events? Based on recent clinical data, this review concludes that the risk of coronary thrombosis on anti-platelet drugs withdrawal is much higher than the risk of surgical bleeding when maintaining them. In secondary prevention, aspirin is a lifelong therapy and should never be stopped. Clopidogrel is mandatory as long as the coronary stents are not fully endothelialized, which takes 6–24 weeks depending on the technique used, but might be required for a longer period

10 Jul 09

Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials

Posted in Anticoagulation, Coronary artery disease at 16:01 by Laci

By Antithrombotic Trialists’ (ATT) Collaboration

Lancet 2009;373:1849-1860.

Low-dose aspirin is of definite and substantial net benefit for many people who already have occlusive vascular disease. We have assessed the benefits and risks in primary prevention.

Methods
We undertook meta-analyses of serious vascular events (myocardial infarction, stroke, or vascular death) and major bleeds in six primary prevention trials (95,000 individuals at low average risk, 660,000 person-years, 3554 serious vascular events) and 16 secondary prevention trials (17,000 individuals at high average risk, 43,000 person-years, 3306 serious vascular events) that compared long-term aspirin versus control. We report intention-to-treat analyses of first events during the scheduled treatment period.

Findings
In the primary prevention trials, aspirin allocation yielded a 12% proportional reduction in serious vascular events (0.51% aspirin vs 0.57% control per year, p=0.0001), due mainly to a reduction of about a fifth in non-fatal myocardial infarction (0.18%vs 0.23% per year, p<0.0001). The net effect on stroke was not significant (0.20%vs 0.21% per year, p=0.4: haemorrhagic stroke 0.04%vs 0.03%, p=0.05; other stroke 0.16%vs 0.18% per year, p=0.08). Vascular mortality did not differ significantly (0.19%vs 0.19% per year, p=0.7). Aspirin allocation increased major gastrointestinal and extracranial bleeds (0.10%vs 0.07% per year, p<0.0001), and the main risk factors for coronary disease were also risk factors for bleeding. In the secondary prevention trials, aspirin allocation yielded a greater absolute reduction in serious vascular events (6.7%vs 8.2% per year, p<0.0001), with a non-significant increase in haemorrhagic stroke but reductions of about a fifth in total stroke (2.08%vs 2.54% per year, p=0.002) and in coronary events (4.3%vs 5.3% per year, p<0.0001). In both primary and secondary prevention trials, the proportional reductions in the aggregate of all serious vascular events seemed similar for men and women.

Interpretation
In primary prevention without previous disease, aspirin is of uncertain net value as the reduction in occlusive events needs to be weighed against any increase in major bleeds. Further trials are in progress.

28 Dec 08

D-Dimer to predict recurrent disease after stopping anticoagulant therapy for unprovoked venous thromboembolism

Posted in Anticoagulation at 0:00 by Laci

By M Verhovsek, J D Douketis, Q Yi, S Shrivastava, R Cl Tait, T Baglin, D Poli and W Lim

Ann Int Med 2008;149:481-490

The optimal duration of anticoagulation for a first episode of unprovoked venous thromboembolism (VTE) is uncertain. Methods for predicting risk for recurrence may identify low-risk patients who are less likely to benefit from prolonged anticoagulation.

Purpose
To synthesize evidence evaluating the value of D-dimer as a predictor of recurrent disease in patients who have stopped anticoagulant therapy after a first unprovoked VTE.

Data sources
The MEDLINE, EMBASE, CINAHL, and Cochrane databases were searched until March 2008 without language restrictions. The strategy was supplemented with manual review of reference lists and contact with content experts.

Study selection
Randomized, controlled trials or prospective cohort studies that measured D-dimer after anticoagulant therapy in patients who received at least 3 months of anticoagulant treatment of unprovoked VTE.

Data extraction
Two authors independently reviewed articles and extracted data.

Data synthesis
Seven studies, totaling 1888 patients with a first unprovoked VTE, were eligible for analysis. During 4500 person-years of follow up, annual rates of recurrent VTE differed statistically significantly: 8.9% (95% CI, 5.8% to 11.9%) in patients with positive D-dimer results and 3.5% (CI, 2.7% to 4.3%) in patients with negative D-dimer results.

Limitation
The duration of anticoagulation, timing of D-dimer testing, and D-dimer assay varied across studies.

Conclusion
In patients who have completed at least 3 months of anticoagulation for a first episode of unprovoked VTE and after approximately 2 years of follow-up, a negative D-dimer result was associated with a 3.5% annual risk for recurrent disease, whereas a positive D-dimer result was associated with an 8.9% annual risk for recurrence. These rates should inform decisions about the balance of risks and benefits of prolonging anticoagulation.

05 Nov 08

Early intravenous unfractionated heparin and mortality in septic shock

Posted in Anticoagulation, Sepsis at 8:00 by Laci

By R Zarychanski, S Doucette, D Fergusson, D Roberts, D Houston, S Sharma, H Gulati, A Kumar

Crit Care Med 2008;36:2973-2979

Sepsis and septic shock represent a systemic inflammatory state with substantial pro-coagulant elements. Unfractionated heparin is a known anticoagulant, which also possesses anti-inflammatory properties. Unfractionated heparin has been shown to increase survival in experimental models of septic shock.

Objective
To evaluate the impact of intravenous therapeutic dose unfractionated heparin in a cohort of patients diagnosed with septic shock.

Design
Retrospective, propensity matched, multicenter, cohort study.

Setting
Regional intensive care units in Winnipeg, Canada between 1989 and 2005.

Patients
Two thousand three hundred fifty-six patients diagnosed with septic shock, of which 722 received intravenous therapeutic dose heparin.

Measurements and Main Results
The primary outcome of study was 28-day mortality, and mortality stratified by severity of illness (Acute Physiologic and Chronic Health Evaluation II quartile). Safety was assessed by comparing rates of gastrointestinal hemorrhage, intracranial hemorrhage, and the need for transfusion. By using a Cox proportional hazards model, systemic heparin therapy was associated with decreased 28-day mortality (307 of 695 [44.2%] vs. 279 of 695 [40.1%]; hazard ratio 0.85 [confidence interval (CI) 95% 0.73-1.00]; p = 0.05). In the highest quartile of severity of illness (Acute Physiologic and Chronic Health Evaluation II score 29-53), heparin administration was associated with a clinically and statistically significant reduction in 28-day mortality [127 of 184 (69.0%) vs. 94 of 168 (56.0%); hazard ratio 0.70 (CI 95% 0.54-0.92); p = 0.01]. The use of intravenous unfractionated heparin was associated with successful liberation from mechanical ventilation [odds ratio of 1.42 (CI 95% 1.13-1.80); p = 0.003], and successful discontinuation of vasopressor/inotropic support [odds ratio of 1.34 (CI 95% 1.06-1.71); p = 0.01]. No significant differences in the rates of major hemorrhage or need for transfusion were identified.

Conclusion
Early administration of intravenous therapeutic dose unfractionated heparin may be associated with decreased mortality when administered to patients diagnosed with septic shock, especially in patients with higher severity of illness. Prospective randomized trials are needed to further define the role of this agent in sepsis and septic shock.

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