Unfractionated heparin (UFH) is used intraoperatively as antithrombotic by most vascular surgeons worldwide during infrainguinal bypass surgery (IABS) to reduce the risk of peroperative and early graft thrombosis. To reduce the harmful side effects of UFH (bleeding complications, HIT) and to reduce peroperative and early graft failure, other pharmaceuticals have been suggested for IABS. A systematic review was performed using MEDLINE, EMBASE and Cochrane databases. Only 9 studies on IABS and intraoperative antithrombotic use were eligible for review. Between studies heterogeneity was high and investigated study populations were often of small size. No study was retrieved comparing UFH to no-UFH. Dextran, human antithrombin and iloprost showed no beneficial effect compared to UFH alone for patency, mortality and morbidity. Low molecular weight heparin (LMWH) has potential benefits compared to UFH, but a statistically significant effect could not be demonstrated from the current review. The use of UFH during IABS to prevent intraoperative graft thrombosis has not been proven in randomized clinical trials. Dextran, human antithrombin and iloprost showed to be of no added beneficial effect for the patient compared to UFH alone. Data on the use of LMWH instead of UFH are promising, but no statistically significant benefit could be reproduced from literature. Results from a recent Cochrane review were favourable for LMWH, but it appeared that included data were not complete in that review. Randomized controlled trials are required for intra-operative use of antithrombotics and to improve peroperative and early patency after IABS.

Optimal management of retinal vein occlusion (RVO) is still a matter of debate. Antithrombotic and fibrinolytic drugs have been investigated after demonstration of a role of thrombosis in the complex pathogenesis of the disease. Aim of our study was to systematically summarise best available evidence on the acute treatment and on the secondary prevention of RVO with antithrombotic and fibrinolytic drugs. A computer-assisted search of the MEDLINE and EMBASE electronic databases up to January 2009 was performed. Two review authors selected all published randomised controlled trials (RCTs) from the search, assessed study quality and extracted data. Based on Jadad's score, RCTs were stratified into three quality categories. A total of six RCTs were included. Only one RCT of high quality was identified. A total of 384 patients were investigated, 234 with central retinal vein occlusion and 150 with branch retinal vein occlusion. No study enrolled more than 100 patients. Three studies compared therapeutic doses of low-molecular-weight heparin (LMWH) with low-dose aspirin, one study compared ticlopidine with placebo and two studies compared intravenous fibrinolytic therapy followed by warfarin or aspirin with either haemodilution or no treatment. A partial improvement of visual acuity was reported in every study, independently of the study drug. No long-term secondary prevention study was published. The present systematic review suggests that antithrombotic therapy, in particular LMWH, may be part of the therapeutic armamentarium for patients with recent onset RVO. No firm recommendation can be provided given the limited available evidence. © Schattauer 2010.

AimHeart failure (HF) is a prothrombotic state, but current evidence does not support the routine use of aspirin, antiplatelet agents, or anticoagulation in these patients in sinus rhythm (SR). We conducted an updated meta-analysis comparing these medications on outcomes in HF.Methods and resultsAll randomized trials in patients with chronic HF and reduced ejection fraction (HFREF) in sinus rhythm (SR; n>100), in which the effect of aspirin, antiplatelet agents, or anticoagulants was determined, were prospectively evaluated. Four trials met the entry criteria. Intervention time was 28 months. No difference in all-cause mortality was seen when aspirin was compared with warfarin [n = 3701, relative risk (RR) 1.00, 95% confidence interval (CI) 0.88-1.13, P = 0.94]. Compared with aspirin, significantly fewer strokes were seen with warfarin (n = 3701, RR 0.59, 95% CI 0.41-0.85, P = 0.004), and fewer fatal and non-fatal ischaemic strokes (n = 3368, RR 0.48, 95% CI 0.32-0.73, P = 0.0006). Warfarin doubled the risk of major haemorrhage compared with aspirin (n = 3701, RR 2.02, 95% CI 1.45-2.80, P < 0.0001); however, intracranial haemorrhage was rare. There was no significant difference in HF hospitalizations with aspirin vs. warfarin (n = 3701, RR 1.16, 95% CI 0.79-1.71, P = 0.45).ConclusionWith warfarin compared with aspirin in HFREF in SR, significant reductions in stroke risk were observed but no mortality benefit was seen. Major haemorrhage doubled but intracranial haemorrhage was rare. These findings suggest that overall the benefit of warfarin in HFREF in SR outweighs the risk. Aspirin use did not increase HF hospitalization as has been previously suggested. © 2012 The Author.

CRD SUMMARY:

This review, of largely retrospective data, concluded that the optimal regimen for antithrombotic therapy in the first 90 days after tissue aortic valve replacement remained unclear because of methodological limitations in the included studies. Due to methodological flaws in the review process, the authors' conclusion may not be reliable.

Background: Development of clinical practice guidelines involves making trade-offs between desirable and undesirable consequences of alternative management strategies. Although the relative value of health states to patients should provide the basis for these trade-offs, few guidelines have systematically summarized the relevant evidence. We conducted a systematic review relating to values and preferences of patients considering antithrombotic therapy. Methods: We included studies examining patient preferences for alternative approaches to antithrombotic prophylaxis and studies that examined, in the context of antithrombotic prophylaxis or treatment, how patients value alternative health states and experiences with treatment. We conducted a systematic search and compiled structured summaries of the results. Steps in the process that involved judgment were conducted in duplicate. Results: We identified 48 eligible studies. Sixteen dealt with atrial fibrillation, five with VTE, four with stroke or myocardial infarction prophylaxis, six with thrombolysis in acute stroke or myocardial infarction, and 17 with burden of antithrombotic treatment. Conclusion: Patient values and preferences regarding thromboprophylaxis treatment appear to be highly variable. Participant responses may depend on their prior experience with the treatments or health outcomes considered as well as on the methods used for preference elicitation. It should be standard for clinical practice guidelines to conduct systematic reviews of patient values and preferences in the specific content area. © 2012 American College of Chest Physicians.

BACKGROUND:

Patient preferences and expert-generated clinical practice guidelines regarding treatment decisions may not be identical. The authors compared the thresholds for antithrombotic treatment from studies that determined or modeled the treatment preferences of patients with atrial fibrillation with recommendations from clinical practice guidelines.

METHODS:

Methods included MEDLINE identification, systematic review, and pooling with some reanalysis of primary data from relevant studies.

RESULTS:

Eight pertinent studies, including 890 patients, were identified. These studies used 3 methods (decision analysis, probability tradeoff, and decision aids) to determine or model patient preferences. All methods highlighted that the threshold above which warfarin was preferred over aspirin was highly variable. In 6 of 8 studies, patient preferences indicated that fewer patients would take warfarin compared to the recommendations of the guidelines. In general, at a stroke rate of 1% with aspirin, half of the participants would prefer warfarin, and at a rate of 2% with aspirin, two thirds would prefer warfarin. In 3 studies, warfarin must provide at least a 0.9% to 3.0% per year absolute reduction in stroke risk for patients to be willing to take it, corresponding to a stroke rate of 2% to 6% on aspirin.

CONCLUSIONS:

For patients with atrial fibrillation, treatment recommendations from clinical practice guidelines often differ from patient preferences, with substantial heterogeneity in their individual preferences. Since patient preferences can have a substantial impact on the clinical decision-making process, acknowledgment of their importance should be incorporated into clinical practice guidelines. Practicing physicians need to balance the patient preferences with the treatment recommendations from clinical practice guidelines.

Guidelines recommend that patients' values and preferences should be considered when selecting stroke prevention therapy for atrial fibrillation (SPAF). However, doing so is difficult, and tools to assist clinicians are sparse. We performed a narrative systematic review to provide clinicians with insights into the values and preferences of AF patients for SPAF antithrombotic therapy. Narrative systematic review of published literature from database inception.

RESEARCH QUESTIONS:

1) What are patients' AF and SPAF therapy values and preferences? 2) How are SPAF therapy values and preferences affected by patient factors? 3) How does conveying risk information affect SPAF therapy preferences? and 4) What is known about patient values and preferences regarding novel oral anticoagulants (NOACs) for SPAF? Twenty-five studies were included. Overall study quality was moderate. Severe stroke was associated with the greatest disutility among AF outcomes and most patients value the stroke prevention efficacy of therapy more than other attributes. Utilities, values, and preferences about other outcomes and attributes of therapy are heterogeneous and unpredictable. Patients' therapy preferences usually align with their values when individualised risk information is presented, although divergence from this is common. Patients value the attributes of NOACs but frequently do not prefer NOACs over warfarin when all therapy-related attributes are considered. In conclusion, patients' values and preferences for SPAF antithrombotic therapy are heterogeneous and there is no substitute for directly clarifying patients' individual values and preferences. Research using choice modelling and tools to help clinicians and patients clarify their SPAF therapy values and preferences are needed.

OBJECTIVE:

We performed a network meta-analysis to investigate the optimal antithrombotic regime by indirectly comparing new antithrombotic regimes (new P2Y12 inhibitors plus aspirin or novel oral anticoagulants on top of traditional dual antiplatelet therapy [DAPT]) in patients with acute coronary syndrome (ACS).

METHODS:

A systematic search of MEDLINE, EMBASE, and the Cochrane databases was performed to identify all phase 3 randomized controlled trials (RCTs) involving novel oral anticoagulants or oral P2Y12 inhibitors in patients with ACS. Major adverse cardiac events (MACE) were regarded as the efficacy endpoint, and thrombolysis in myocardial infarction (TIMI) major bleeding events were used as the safety endpoint. The net clinical benefit was calculated as the sum of MACE and TIMI major bleeding events.

RESULTS:

Five phase 3 RCTs with 64,476 ACS patients were included. Although there were no significant differences among new antithrombotic regimes, rivaroxaban 5 mg twice daily plus traditional DAPT might be the most effective in reducing the incidence of MACE, accompanying the highest risk of TIMI major bleeding. Ticagrelor plus aspirin presented slight advantage on the net clinical benefit over other new antithrombotic regimes, with the highest probability of being the best regimes for net clinical benefit (35.0%), followed by prasugrel plus aspirin (28.0%), and rivaroxaban 2.5 mg twice daily plus traditional DAPT (19.5%).

CONCLUSION:

Novel antithrombotic regime with ticagrelor plus aspirin brings a larger clinical benefit in comparison with other regimes, suggesting that it may be the optimal antithrombotic regime for patients with ACS.

STUDY DESIGN:

Systematic review

STUDY RATIONALE AND CONTEXT:

There is controversy regarding the efficacy and safety of chemical prophylaxis to prevent deep venous thrombosis (DVT) and pulmonary embolism (PE) in elective spinal procedures.Commonly performed elective spine surgeries done through a posterior approach have a very low associated risk of DVT/PE. The lack of consensus is due in part to a limited amount of quality evidence based literature dealing with this issue.

OBJECTIVE:

To compare chemical prophylaxis with no chemical prophylaxis in preventing venous thromboembolism in elective thoracolumbar spine surgery.

METHODS:

We undertook a systematic review of the literature to assess the efficacy and safety of chemical prophylaxis in preventing venous thromboembolism in elective thoracolumbar spine surgery. Pubmed, EMBASE, Cochrane, National Guideline Clearinghouse Databases as well as bibliographies of key articles were searched. Articles were reviewed by two independently working reviewers. Inclusion and exclusion criteria were set and each article was subject to a predefined quality rating scheme.

RESULTS:

We identified only two articles meeting our inclusion criteria. Neither study demonstrated a significant difference between chemical prophylaxis versus no prophylaxis in preventing thromboembolic events. There was an increased incidence of perioperative bleeding with low dose Coumadin in one of the studies.

CONCLUSION:

The incidence of DVT and PE in commonly performed elective posterior spinal procedures is very low. While there is a limited amount of randomized literature looking at this issue, the current literature does not support the routine use of chemical prophylaxis for low risk patients undergoing these procedures.

PURPOSE:

The efficacy and safety of triple antithrombotic therapy in patients with atrial fibrillation (AF) who undergo percutaneous coronary intervention (PCI) with stent implantation are reviewed.

SUMMARY:

A systematic literature search of PubMed, EMBASE, and International Pharmaceutical Abstracts identified a total of 10 cohort studies and one meta-analysis investigating triple antithrombotic therapy in this patient population. With respect to efficacy, evidence from nonrandomized studies supports the superiority of triple antithrombotic therapy over dual antiplatelet therapy at preventing major adverse cardiac events and all-cause mortality. With respect to safety, the heterogeneous methodology and definitions for bleeding in the studies do not allow for easy interpretation and quantification of bleeding risk. There appears to be qualitative consistency that the rate of bleeding is higher with triple antithrombotic therapy compared with dual antiplatelet therapy. The meta-analysis, as well as a recent large registry data cohort study, demonstrated a twofold increase in the risk of major bleeding with triple antithrombotic therapy.

CONCLUSION:

The heterogeneous methodology of the available studies does not allow for conclusive interpretation and quantification of the efficacy and safety of triple antithrombotic therapy in patients with AF undergoing PCI with stent implantation compared with dual antiplatelet therapy. Evidence from small cohort studies support the benefit of triple antithrombotic therapy at reducing major adverse cardiac events and all-cause mortality with higher rates of bleeding.