10 Jul 09
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.
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28 Dec 08
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.
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05 Nov 08
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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22 Jan 07
Posted in Anesthesia, Anticoagulation, Pre-operatie evaluation at 20:08 by Laci
By CL Grines, RO Bonow, DE Casey Jr, TJ Gardner, PB Lockhart, DJ Moliterno, P O’Gara and P Whitlow
Circulation 2007; 115:813-818
Dual antiplatelet therapy with aspirin and a thienopyridine has been shown to reduce cardiac events after coronary stenting. However, many patients and healthcare providers prematurely discontinue dual antiplatelet therapy, which greatly increases the risk of stent thrombosis, myocardial infarction, and death. This advisory stresses the importance of 12 months of dual antiplatelet therapy after placement of a drug-eluting stent and educating the patient and healthcare providers about hazards of premature discontinuation. It also recommends postponing elective surgery for 1 year, and if surgery cannot be deferred, considering the continuation of aspirin during the perioperative period in high-risk patients with drug-eluting stents.
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