|Antiplatelet versus anticoagulation therapy after extracardiac conduit Fontan: a systematic review and meta-analysis
|Marrone C, Galasso G, Piccolo R, de Leva F, Paladini R, Piscione F, Santoro G
This review concluded that the rate of thromboembolic and bleeding events were similar for antiplatelet and anticoagulation therapy in patients who underwent an extracardiac conduit Fontan procedure. The conclusions reflect the evidence presented, but the reliability of the evidence base is limited by the study design, sample sizes and very low numbers of events recorded across the studies.
To determine the incidence of thromboembolism among patients undergoing extracardiac conduit Fontan procedure who received prophylactic anticoagulation or antiplatelet therapy.
MEDLINE was searched with no language restrictions from inception to February 2010; search terms were reported. Reference lists of retrieved articles, conference abstracts of four relevant journals, clinicaltrialresults.org, and the websites of three relevant societies were also searched.
Studies that evaluated primary extracardiac conduit Fontan procedures in patients who received clearly reported anticoagulation or antiplatelet regimens were eligible for inclusion. Eligible studies had to enroll at least five patients using a clearly reported selection procedure and have follow-up of at least two months. Ongoing studies were excluded.
Most studies used aspirin as the antiplatelet therapy in doses that ranged from 1 to 10mg/kg/day or 81 to 325mg/day (where reported); 5mg/kg/day ticlopidine was also used. Dose adjusted warfarin was the most commonly used anticoagulant; the target international normalised ratio varied across studies from 1.5/2.0 to 2.5/3.0, when reported. The median age of patients at the time of the extracardiac conduit Fontan procedure ranged from 1.5 to 13.2 years. Most conduits were made from polytetrafluoroethylene; zero to 86% were fenestrated (where reported).
Two reviewers independently assessed studies for inclusion in the review; disagreements were resolved by consensus.
Assessment of study quality
Study quality was assessed using direction of data collection, enrolment procedure, outcome assessment and loss to follow-up (<5%, 5% to 10%, >10%).
It was unclear how many reviewers assessed study quality.
The incidence of stroke, pulmonary embolism, intracardiac or deep vein thrombosis, and early (up to 30 days) and late (over 30 days) post-extracardiac conduit Fontan procedure reversible neurologic deficits were extracted; rates of thromboembolic events with 95% confidence intervals (CIs) were calculated. The incidence of bleeding events were also extracted and bleeding rates with 95% confidence intervals calculated.
It was unclear how many reviewers extracted data.
Methods of synthesis
Summary thromboembolic and bleeding rates, with 95% confidence intervals, were calculated using a DerSimonian and Laird random-effects model; results for patients who received antiplatelet and anticoagulant therapies were presented separately along with overall results.
Heterogeneity was assessed using X2 and I2. I2 over 50% was considered high heterogeneity.
Publication bias was assessed using a funnel plot.
Results of the review
Twenty studies met the inclusion criteria (1,070 patients underwent extracardiac conduit Fontan procedure; range 6 to 282). Of the 20 studies, 19 were retrospective, 17 enrolled patients consecutively, 18 used imaging and clinical examination for the outcome assessment. Fifteen studies had lower than 5% loss to follow-up; four had from 5 to 10%. Mean follow-up ranged from two to 120 months (where reported). Seven studies evaluated patients receiving antiplatelets, three evaluated patients receiving anticoagulation and 10 evaluated patients receiving both (seven of these patients moved onto antiplatelet therapy alone after three to 12 months).
Overall, 16 early and 19 late thromboembolic events occurred; the summary thromboembolic rate was 5.2% (95% CI 3.8% to 7.0%). The thromboembolic rates were similar between patients who had received antiplatelet (4.5%, 95% CI 2.3 to 8.8) and anticoagulation (5.0%, 95% CI 3.1 to 8.1) therapies. The rate of early thromboembolic events were similar between patients who received warfarin (3.0%, 95% CI 3.8 to 7.0) and those who received antiplatelet therapy alone (3.7%, 95% CI 1.8 to 7.6). Statistical heterogeneity was not observed for any analysis. Only two bleeding events were recorded, both in patients who received anticoagulation therapy.
For patients who underwent extracardiac conduit Fontan procedure, the rate of thromboembolic and bleeding events associated with antiplatelet therapy was similar to that associated with anticoagulation therapy.
The review addressed a clear research question supported by appropriate inclusion criteria. One database was searched, which was supplemented with some handsearching, but publication bias could not be ruled out; results of the funnel plot were not reported. Study selection was conducted in duplicate, but similar methods to reduce error and bias were not reported for the data extraction or quality assessment.
Study quality was assessed using appropriate criteria; the results were reported in summary form, so it was not possible to determine the quality of individual studies.
Although the conclusions reflect the evidence presented, it should be borne in mind that the studies were mainly small and retrospective, with very low absolute numbers of events, limiting the reliability of the evidence base.
Implications of the review for practice and research
Practice: The authors did not report any implications for practice.
Research: The authors stated that the findings of the review need to be confirmed and independent predictors identified using randomised controlled trials or analysis of patient-level data in observational studies.
Marrone C, Galasso G, Piccolo R, de Leva F, Paladini R, Piscione F, Santoro G. Antiplatelet versus anticoagulation therapy after extracardiac conduit Fontan: a systematic review and meta-analysis. Pediatric Cardiology 2011; 32(1): 32-39
Subject indexing assigned by NLM
Anticoagulants /therapeutic use; Fontan Procedure /adverse effects /methods; Humans; Platelet Aggregation Inhibitors /therapeutic use; Thromboembolism /etiology /prevention & control; Treatment Outcome
Database entry date
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.