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Original Research: ANTITHROMBOTIC THERAPY |

Safety of Uninterrupted Anticoagulation in Patients Requiring Elective Coronary Angiography With or Without Percutaneous Coronary Intervention: A Systematic Review and Metaanalysis FREE TO VIEW

Erin Jamula, MSc; Nancy S. Lloyd, MSc; Jon-David Schwalm, MD; K. E. Juhani Airaksinen, MD; James D. Douketis, MD, FCCP
Author and Funding Information

From the Department of Medicine (Mss Jamula and Lloyd and Drs Schwalm and Douketis), McMaster University and St Joseph’s Healthcare, Hamilton, ON, Canada; and the Department of Medicine (Dr Airaksinen), Turku University Hospital, Turku, Finland.

Correspondence to: James D. Douketis, MD, FCCP, St Joseph’s Healthcare, Room F-544, 50 Charlton Ave E, Hamilton, ON L8N 4A6, Canada; e-mail: jdouket@mcmaster.ca


For editorial comment see page 771

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;138(4):840-847. doi:10.1378/chest.09-2603
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Background:  Patients who are receiving vitamin K antagonist (VKA) therapy pose challenges when they require surgery or invasive procedures because the risk for bleeding during the procedure must be balanced against the risk of an atherothrombotic event if the VKA is interrupted. However, it may be possible to safely perform some procedures, such as coronary angiography with or without percutaneous coronary intervention (PCI), without VKA interruption.

Methods:  We undertook a systematic review and metaanalysis to assess the safety of a periprocedural management strategy of uninterrupted VKA (U-VKA) vs interrupted VKA (I-VKA) with or without bridging with low-molecular-weight heparin in patients undergoing elective coronary angiography with or without PCI.

Results:  Eight studies were included in the review. Most were of moderate to very low quality. A strategy of U-VKA appears to confer approximately one-half the risk (odds ratio, 0.43; 95% CI, 0.26-0.73) of experiencing an access site bleeding complication within 1 week of the procedure compared with a strategy of I-VKA. The U-VKA strategy was associated with a pooled access site bleeding complication rate of 4.0% (95% CI, 3.0-7.0), and although high heterogeneity precluded pooling of such a rate in the I-VKA group, these rates ranged from 2% to 14%.

Conclusion:  Although it appears that coronary angiography with or without PCI can be safely performed without interrupting VKA, the low methodologic quality of existing studies precludes any definitive conclusions. Randomized trials assessing different anticoagulation strategies are needed to establish evidence-based practice guidelines in this setting.

Figures in this Article

Patients who are receiving vitamin K antagonist (VKA) therapy pose challenges when they require surgery or other invasive procedures because the risk for bleeding during the procedure with continuation of the VKA must be balanced against the risk of an atherothrombotic event if the VKA is interrupted. Current periprocedural anticoagulation strategies include interrupting VKA therapy for 5 days prior to the procedure; interrupting VKA and administering bridging anticoagulation, typically with a low-molecular-weight heparin; or continuing the VKA at the time of the procedure.1

An increasing number of procedures are being done in VKA-treated patients without interruption of VKA therapy. With careful attention to local hemostasis, procedures such as dental extraction, cataract removal, and pacemaker implantation have been safely performed in anticoagulated patients.1,2 These findings highlight the possibility that uninterrupted anticoagulation may be appropriate for coronary angiography, especially because a considerable proportion of such patients also receive VKA therapy.3 The potential advantages of uninterrupted VKA (U-VKA) therapy include a minimized risk for atherothrombotic events, obviating the need for bridging therapy, and simplified periprocedural management.

Evidence-based guidelines regarding periprocedural anticoagulation in this setting are lacking, and it is assumed that continuing VKA during angiography or percutaneous coronary intervention (PCI) will increase bleeding and access site complications.4 Another concern is the impact on bleeding rates of continued VKA in conjunction with coadministration of periprocedural anticoagulation and antiplatelet therapy, especially during the procedure as well as after PCI where triple therapy consisting of VKA, aspirin, and clopidogrel is recommended. Thus, typical periprocedural anticoagulation management includes VKA interruption with or without heparin bridging.5

Against this background, we aimed to determine, in patients requiring elective coronary angiography with or without PCI, the incidence of bleeding in those who had U-VKA and in those in whom VKA was interrupted prior to the procedure with or without heparin bridging. We also assessed the perioperative incidence of atherothrombotic and other adverse clinical events.

Literature Search

We searched the MEDLINE, EMBASE, CINAHL, and Cochrane Library electronic databases. Abstracts were screened independently by two reviewers (E. J., N. S. L.). BIOSIS Previews and clinicaltrials.gov also were searched. Reference lists of included articles were reviewed manually, as were issues of key journals that had yet to be indexed electronically. Authors were contacted if additional information or clarification was required. Additionally, the corresponding authors of included articles were contacted in an attempt to obtain articles potentially overlooked by the initial search.

There were no language restrictions, but the number of years was arbitrarily restricted to the past 15 (1993 to present) to more accurately capture outcomes related to contemporary angiography and PCI techniques and periprocedural anticoagulation management. Disagreements regarding article inclusion were resolved by consensus and, if required, discussion with a third reviewer (J. D. D.). Details of the literature search are found in e-Appendix 1.

Study Eligibility

Articles were included if they met all of the following criteria: (1) Patients were undergoing coronary angiography with or without PCI; (2) Some or all patients were receiving a VKA prior to the procedure and remained on it throughout the procedure (ie, U-VKA); (3) The study assessed how anticoagulants were managed during the periprocedural period; and (4) The study assessed bleeding outcomes. Articles were excluded if solely postoperative anticoagulant strategies were assessed and if results for patients in whom VKA was interrupted were not reported separately. Narrative reviews, case reports, commentaries, and letters to the editor also were excluded. The risk for publication bias was assessed through the creation of funnel plots for each pooled outcome.

Study Quality

Randomized controlled trials were assessed using the previously validated Cochrane Collaboration Tool for Assessing the Risk of Bias.6 Cohort studies, case-control studies, and case series were assessed using the previously validated Newcastle-Ottawa Scale.7 The lack of a comparator group in the case series and the resulting lower methodologic quality of this study design were reflected through a lower score on the Newcastle-Ottawa Scale. Quality was rated by two independent reviewers (E. J., B. A.), with disagreements resolved by consensus.

Data Extraction

Data extraction was performed independently by two reviewers (E. J., N. S. L.) using a standard form. Disagreements were resolved by consensus. The data abstraction form is provided in e-Appendix 2. We defined the periprocedural period as the period starting 1 week before the procedure and ending 1 week after the procedure. This is when events related to periprocedural anticoagulation management are most likely to occur, and we aimed to focus on bleeding that was procedure-related rather than bleeding due to other causes.8

Statistical Analyses

Statistical analyses were performed with RevMan, version 5.0 (Cochrane IMS; Copenhagen, Denmark). Unweighted κ scores were calculated using the PC-AGREE software program (R. Cook, McMaster University; Hamilton, ON, Canada). Outcomes were pooled using the random effects model. Where appropriate, odds ratios (ORs) were determined and pooled using the Mantel-Haenszel method.6,9,10 ORs were expressed such that an OR < 1 favors a strategy of uninterrupted anticoagulation. To pool raw event rates, proportions were first converted to a natural logarithmic scale using Microsoft Excel 2007 (Microsoft Corp; Redmond, WA). If no events occurred, 0.5 was added to that cell to calculate the natural logarithm and was represented in the forest plot as an event rate of 0.1. The δ method was used to calculate the standard error for proportions.11 The inverse variance method then was used to pool the natural logarithm of the event rates.6

The degree of heterogeneity was expressed quantitatively through the Cochran χ2 test and the I2 value.6 A priori, potential sources of heterogeneity, including study design and technical and angiography procedure-related aspects, were identified, which were to be explored with sensitivity analyses if significant heterogeneity was identified.

Study Selection

The study selection process and reasons for exclusion are described in Figure 1. From an original result of 722 articles, 697 were excluded based on title and abstract (κ = 0.8). Twenty-five articles were retrieved for full-text review, and eight of these were included in the review (κ = 0.82).3,4,1217

Figure Jump LinkFigure 1. Study selection (quality of reporting of metaanalysis flowchart). See e-Appendix 3 for excluded references. LMWH = low-molecular-weight heparin; VKA = vitamin K antagonist.Grahic Jump Location
Study Characteristics

Table 1 lists the characteristics of the included studies. Four were cohort studies, one of which was prospective.4,1214 One was a randomized trial that included an additional cohort of patients who could not be randomized but still underwent the procedure without interruption of their anticoagulation.15 The remaining three studies were case series, two of which were prospective.3,16,17

Table Graphic Jump Location
Table 1 —Characteristics of Included Studies

Cath = catheterization; F = femoral; INR = international normalized ratio; I-VKA = interrupted vitamin K antagonist; N/A = not applicable; PCI = percutaneous coronary intervention; pros = prospective; R = radial; RCT = randomized controlled trial; retro = retrospective; U-VKA = uninterrupted vitamin K antagonist.

a 

Day of procedure.

b 

Study consisted of warfarin group and control group of unanticoagulated patients; within the warfarin group, some patients were managed with U-VKA and others with I-VKA.

c 

Age not reported separately for each VKA strategy.

d 

Access site not reported separately for U-VKA and I-VKA.

e 

Only the range was provided.

f 

Twenty-five procedures in 23 patients.

g 

Control group consisted of nonanticoagulated patients.

h 

Breakdown of men by VKA strategy not reported.

i 

Age not reported separately for each VKA strategy.

The patient population was similar across studies and consisted of elderly patients in which atrial fibrillation was the most common indication for VKA therapy (69.6% of patients); other indications were a mechanical heart valve (7.1%), prior stroke (8.1%), and venous thromboembolism (4.9%). Six studies included patients who had PCI,3,4,1417 whereas two reported only patients undergoing angiography.12,13 Four studies compared a strategy of uninterrupted anticoagulation vs interrupting VKA with or without heparin bridging,4,12,14,15 and a fifth had a control group of nonanticoagulated patients.13 In terms of vascular access site, three studies used only femoral access,3,14,15 two used a radial artery access,16,17 and the remainder used a combination of both approaches.4,12,13

The mean international normalized ratio (INR) on the day of the procedure in the U-VKA groups ranged from 1.99 to 2.5, which is in the lower range of the therapeutic anticoagulation levels.18 The mean INR in the interrupted VKA (I-VKA) groups on the day of the procedure was between 1.5 and 1.9. Use of antiplatelet drugs varied widely across studies (Table 2).

Table Graphic Jump Location
Table 2 —Periprocedural Antiplatelet Agent Use

AP = antiplatelet; ASA = acetylsalicylic acid, GPI = glycoprotein IIb/IIa inhibitor; LMWH = low-molecular-weight heparin; N/A = not applicable; NR = not reported; UFH = unfractionated heparin. See Table 1 legend for expansion of other abbreviations.

a 

Control group of nonanticoagulated patients; U-VKA group consisted of all VKA patients regardless of management strategy.

b 

ASA + a thienopyridine.

c 

Specifically, ASA and clopidogrel.

All studies reported bleeding events; however, such events were defined differently among studies, and some studies did not provide a definition. The majority of studies reported vascular access site complications that varied slightly in definition but always included pseudoaneurysm or arteriovenous fistula. Four studies included stroke or other atherothrombotic events as outcomes.4,1214 The follow-up period of the studies ranged from hospital discharge to 3 months, but only events occurring in the first week after the procedure were included in the pooled analyses, as previously discussed.

Study Quality

e-Appendix 4 provides detailed findings of the study quality assessments. The Cochrane Collaboration Tool for Assessing the Risk of Bias6 was used for one study. The remaining seven were assessed with the Newcastle-Ottawa Scale7 for cohort studies. The main methodological limitation was a lack of controlling for relevant factors such as age, sex, or nature of the procedure, which affects the comparability of the two cohorts. Agreement between reviewers on the quality assessments was substantial (κ = 0.775).19

Study Outcomes

The study outcomes are shown in Table 3. Raw agreement between reviewers for INR values and raw outcomes on the data abstraction form was 90.6%. As shown in Figure 2 and Table 4, the pooled unadjusted OR for bleeding events and vascular access site complications combined in studies with comparator groups was 0.43 (95% CI, 0.26-0.73), with no significant heterogeneity (I2 = 0%; 95% CI, 0-83; P = .43). The overall event rate for the U-VKA group using all studies was 0.04 (95% CI, 0.03-0.07), with no significant heterogeneity (I2 = 0%; 95% CI, 0-62; P = .47). Pooling of event rates for an I-VKA strategy in studies where this strategy was used was inappropriate because of high heterogeneity (I2 = 78%; 95% CI, 42-91; P = .003).

Table Graphic Jump Location
Table 3 —Outcomes

ACE = adverse clinical event; MI = myocardial infarction. See Tables 1 and 2 legends for expansion of other abbreviations.

a 

Event descriptions, No. (%): for I-VKA, death, 2 (0.7); MI, 6 (2.1); target vessel revascularization, 2 (0.7); and stent thrombosis, 1 (0.4); and for U-VKA, death, 8 (3.3); MI; 8 (3.3); target vessel revascularization, 4 (1.7); and stent thrombosis 4 (1.7).

Figure Jump LinkFigure 2. Pooled odds ratio for bleeding and access site events in studies comparing uninterrupted VKA (U-VKA) vs interrupted VKA (I-VKA). The “favors experimental” side refers to a strategy of U-VKA, whereas the “favors control” side refers to I-VKA. M-H = Mantel-Haenszel test.Grahic Jump Location
Table Graphic Jump Location
Table 4 —Pooled Odds Ratio for Bleeding and Access Site Events in Studies Comparing U-VKA vs I-VKA

Heterogeneity: τ2 = 0.00; χ2 = 2.75; df = 3; P = .43; I2 = 0%. Test for overall effect: Z = 3.17; P = .002. df = degrees of freedom; M-H = Mantel-Haenszel test. See Table 1 legend for expansion of other abbreviations.

Bleeding events and access site complications were combined to create one overall event rate, because the definition of a bleeding event in some studies overlapped with that of an access site complication in other studies. The only atherothrombotic events occurred in one study where there was one stroke in the U-VKA group and two strokes in the I-VKA group.4 A description of other adverse clinical events is shown in Table 3.

Our main finding is that a periprocedural strategy of uninterrupted anticoagulation in VKA-treated patients who require coronary angiography may be at least as safe as a strategy of VKA interruption with or without bridging therapy. The U-VKA strategy did not appear to confer higher bleeding rates in PCI-treated patients, but more definitive conclusions relating to such patients are precluded because there were only two studies where all patients had PCI.

It is important to note that the pooled bleeding event rate was dominated by a single study,4 which contributed most of the bleeding and atherothrombotic events. In this study, all patients had PCI, and it was only in this study in which a U-VKA strategy was associated with fewer bleeding events (OR, 0.34; 95% CI, 0.18-0.63). This study also had the highest number of adverse clinical events and was the only study in which any patients experienced a stroke (two with I-VKA and one with U-VKA).4 This finding is important, because a strategy that decreases bleeding is of less clinical value if it also increases atherothrombotic or other adverse events. However, even when all adverse events were grouped together, the U-VKA strategy was still favored (OR, 0.56; 95% CI, 0.35-0.91).4 Grouping of all adverse events in each of the remaining studies that reported atherothrombotic or other adverse events did not result in statistically significant ORs.1214

It is noteworthy that in the study by Karjalainen et al4 antiplatelet drug use differed in the U-VKA and I-VKA groups. Because use of these drugs also can increase bleeding, differential use could affect bleeding event rates independent of the perioperative anticoagulation strategy. Thus, the use of glycoprotein IIa/IIb inhibitors (GPIs) in this study was higher in the I-VKA group (P < .001), and GPI use appeared to be a predictor of major bleeding (OR, 3.0; 95% CI, 1.0-9.1). After obtaining original study data from the authors, further post hoc analysis using the Fisher exact test showed a significant association between the use of periprocedural GPI and major bleeding across all patients (P < .001). However, when applying this test to assess bleeding in clopidogrel users and nonusers, the incidence of major bleeding was not significantly different between those who received clopidogrel and those who did not. Thus, the increased use of GPI in the I-VKA group may have accounted for the higher bleeding rate observed with this strategy. An additional factor that may have led to the higher bleeding rate in the I-VKA group was the significantly higher incidence of heparin use in the I-VKA group.4 Use of heparin for bridging as well as during the procedure also could play a role in the observed bleeding events.

Another factor that may influence event rates, especially bleeding, is the angiography access site. It has been suggested that the radial artery approach is potentially safer for anticoagulated patients because it confers a lower risk for bleeding requiring transfusion and access site complications than the femoral route.20,21 Both approaches were used in anticoagulated patients across the included studies. Two studies found that femoral access was independently predictive of access site complications.4,12 However, femoral artery access did not appear to be associated with an increased risk for bleeding in the remaining reports.

The timing of VKA interruption might have affected bleeding rates in the I-VKA group because the longer the period of interruption, the lower the INR and, hence, the lower the bleeding risk. In studies that included an I-VKA group, none used a standardized periprocedural anticoagulation regimen. The mean time of VKA interruption was 2 to 4 days before the procedure, which is fewer than the 5 days recommended by practice guidelines.5 It is likely, therefore, that a residual anticoagulant effect remained in some patients managed in this way, as shown by the mean INR of 1.5-1.9 at the time of angiography in these studies.5,22,23 Despite this finding, almost all I-VKA groups had low rates of bleeding.12,14,15 Thus, even in the presence of a mild residual anticoagulant effect, it may not lead to clinically important increased bleeding in this setting.

This review has several strengths. First, a precise set of a priori inclusion criteria and duplicate review at each step of the review process minimized the study selection bias. Previously validated tools were used for study quality assessment, and a standardized data abstraction sheet was created to optimize consistency between reviewers.18,19 All studies directly addressed the review question regarding the safety of uninterrupted anticoagulation strategies in patients undergoing coronary angiography, and included populations that are typical of anticoagulated patients. Second, indications for cardiac catheterization were similar across studies; thus, the results should be applicable to the typical VKA-treated patient who requires cardiac catheterization. Study similarities also were reflected by the low heterogeneity when results were pooled. Third, the mean INR levels within each group (U-VKA and I-VKA) across all studies were within 0.5 units of one another, which are unlikely to be clinically important differences, and likely contributed to the low degree of heterogeneity. Further, they can more precisely inform clinical management regarding an INR range in cases in which it remains safe to perform coronary angiography with or without PCI.

This review has several limitations. First, some of the included studies only evaluated patients who had angiography, whereas others only evaluated those who underwent PCI or reported a mix of both. Because angiography alone and angiography plus PCI carry different risks of bleeding and thrombotic complications, we acknowledge that ideally we would report separate pooled outcomes for each procedure. However, it was not possible to separate patients undergoing angiography vs PCI in the studies that reported on both, and there were too few studies of either procedure alone to present any meaningful pooled outcomes. Second, only one study was a randomized controlled trial with the potential that in the remaining observational studies, confounding characteristics were not evenly distributed between intervention groups. Third, with the exception of one study,4 all studies were small and likely underpowered to detect differences between groups. Fourth, the short follow-up period of several studies could underestimate the bleeding rate, despite reports that most bleeds occur within the first 2 weeks after the procedure.5 Fifth, there was no standardized definition for bleeding, which sometimes overlapped in terms of bleeding event and access site bleeding complication; therefore, it was not possible to provide separate event rates for bleeding vs access site bleeding complications. Additionally, the lack of distinction within the I-VKA groups between those patients who were bridged with low-molecular-weight heparin and those who simply had VKA interrupted prior to the procedure without bridging is another problem. The preprocedural anticoagulant therapy (or lack thereof) could have a large impact on the occurrence of both bleeding and atherothrombotic events. Finally, because of differences in reporting and the lack of any standardized protocol for periprocedural administration of aspirin and clopidogrel, it was not possible to evaluate the potentially important impact of these drugs on bleeding rates.

In terms of existing clinical practice guidelines for the management of VKA-treated patients who require PCI, two expert consensus groups have provided recommendations for patients with chronic atrial fibrillation. The European Society of Cardiology suggests that in patients at moderate to high risk of atherothromboembotic events, a strategy of U-VKA is preferred as is use of radial artery access.24 If the procedure requires VKA interruption for > 48 h, heparin bridging can be used, but this has the potential to increase the risk for bleeding. Therefore, it is also suggested that for many patients who require PCI, short interruption of the VKA prior to the procedure will be safe.24 After the procedure, both the European Society of Cardiology24 and practice guidelines by Rubboli et al25 recommend VKA, aspirin, and clopidogrel for at least 1 month for bare-metal stents and for at least 3 to 6 months for drug-eluting stents followed by lifelong VKA therapy. The guidelines by Rubboli et al,25 although limited by the methodological quality of the included studies, seem to support a strategy of U-VKA in this clinical setting.

In conclusion, a periprocedural strategy of uninterrupted anticoagulation for patients on VKA who require coronary angiography with or without PCI appears to be at least as safe as a strategy of U-VKA with or without heparin bridging. This conclusion is tempered because the findings were heavily driven by one study, and the remaining studies were of moderate to very low quality. Well-designed randomized controlled trials are needed to assess the safety of a U-VKA strategy for angiography as well as for PCI and to determine whether this strategy reduces bleeding compared with a VKA interruption strategy with or without heparin bridging.

Author contributions:Ms Jamula: contributed to the study concept and design; data acquisition, analysis, and interpretation; drafting of the manuscript; and critical revision of the manuscript for key intellectual content.

Ms Lloyd: contributed to the data acquisition, analysis, and interpretation.

Dr Schwalm: contributed to the critical revision of the manuscript for key intellectual content.

Dr Airaksinen: contributed to the data analysis and interpretation and critical revision of the manuscript for key intellectual content.

Dr Douketis: contributed to the study concept and design; data analysis and interpretation; and critical revision of the manuscript for key intellectual content.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: We thank Brenna Ammons for her assistance with the study quality assessment.

Additional information: The e-Appendices can be found in the Online Supplement at http://chestjournal.chestpubs.org/content/138/4/840/suppl/DC1.

GPI

glycoprotein IIa/IIb inhibitor

INR

international normalized ratio

I-VKA

interrupted vitamin K antagonist

OR

odds ratio

PCI

percutaneous coronary intervention

U-VKA

uninterrupted vitamin K antagonist

VKA

vitamin K antagonist

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Figures

Figure Jump LinkFigure 1. Study selection (quality of reporting of metaanalysis flowchart). See e-Appendix 3 for excluded references. LMWH = low-molecular-weight heparin; VKA = vitamin K antagonist.Grahic Jump Location
Figure Jump LinkFigure 2. Pooled odds ratio for bleeding and access site events in studies comparing uninterrupted VKA (U-VKA) vs interrupted VKA (I-VKA). The “favors experimental” side refers to a strategy of U-VKA, whereas the “favors control” side refers to I-VKA. M-H = Mantel-Haenszel test.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Characteristics of Included Studies

Cath = catheterization; F = femoral; INR = international normalized ratio; I-VKA = interrupted vitamin K antagonist; N/A = not applicable; PCI = percutaneous coronary intervention; pros = prospective; R = radial; RCT = randomized controlled trial; retro = retrospective; U-VKA = uninterrupted vitamin K antagonist.

a 

Day of procedure.

b 

Study consisted of warfarin group and control group of unanticoagulated patients; within the warfarin group, some patients were managed with U-VKA and others with I-VKA.

c 

Age not reported separately for each VKA strategy.

d 

Access site not reported separately for U-VKA and I-VKA.

e 

Only the range was provided.

f 

Twenty-five procedures in 23 patients.

g 

Control group consisted of nonanticoagulated patients.

h 

Breakdown of men by VKA strategy not reported.

i 

Age not reported separately for each VKA strategy.

Table Graphic Jump Location
Table 2 —Periprocedural Antiplatelet Agent Use

AP = antiplatelet; ASA = acetylsalicylic acid, GPI = glycoprotein IIb/IIa inhibitor; LMWH = low-molecular-weight heparin; N/A = not applicable; NR = not reported; UFH = unfractionated heparin. See Table 1 legend for expansion of other abbreviations.

a 

Control group of nonanticoagulated patients; U-VKA group consisted of all VKA patients regardless of management strategy.

b 

ASA + a thienopyridine.

c 

Specifically, ASA and clopidogrel.

Table Graphic Jump Location
Table 3 —Outcomes

ACE = adverse clinical event; MI = myocardial infarction. See Tables 1 and 2 legends for expansion of other abbreviations.

a 

Event descriptions, No. (%): for I-VKA, death, 2 (0.7); MI, 6 (2.1); target vessel revascularization, 2 (0.7); and stent thrombosis, 1 (0.4); and for U-VKA, death, 8 (3.3); MI; 8 (3.3); target vessel revascularization, 4 (1.7); and stent thrombosis 4 (1.7).

Table Graphic Jump Location
Table 4 —Pooled Odds Ratio for Bleeding and Access Site Events in Studies Comparing U-VKA vs I-VKA

Heterogeneity: τ2 = 0.00; χ2 = 2.75; df = 3; P = .43; I2 = 0%. Test for overall effect: Z = 3.17; P = .002. df = degrees of freedom; M-H = Mantel-Haenszel test. See Table 1 legend for expansion of other abbreviations.

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