Evidence-based Synthesis Program Department of Veterans Affairs 

Health Services Research & Development Service 

April 2012 

Comparative Effectiveness 

of Warfarin and Newer Oral 

Anticoagulants for the Long-term 

Prevention and Treatment of Arterial 

and Venous Thromboembolism 

Prepared for: 

Department of Veterans Affairs 

Veterans Health Administration 

Quality Enhancement Research Initiative 

Health Services Research & Development Service 

Washington, DC 20420 

Prepared by: 

Evidence-based Synthesis Program (ESP) Center 

Durham Veterans Affairs Healthcare System 

Durham, NC 

John W. Williams Jr., M.D., M.H.Sc., Director 

Investigators: 

Principal Investigator: 

Soheir S. Adam, M.D. 

Co-Investigators: 

Jennifer R. McDuffie, Ph.D. 

Thomas L. Ortel, M.D., Ph.D. 

John W. Williams Jr., M.D., M.H.Sc. 

Research Associate:
 

Avishek Nagi, M.S.
 

Medical Editor:
 

Liz Wing, M.A.
 
 

 

Warfarin and Newer Oral Anticoagulants: 


Long-term Prevention and Treatment of Arterial and VTE Evidence-based Synthesis Program
 

PREFACE 

Quality Enhancement Research Initiative’s (QUERI’s) Evidence-based Synthesis Program 

(ESP) was established to provide timely and accurate syntheses of targeted healthcare topics 

of particular importance to Veterans Affairs (VA) managers and policymakers, as they work to 

improve the health and healthcare of Veterans. The ESP disseminates these reports throughout 

VA. 

QUERI provides funding for four ESP Centers and each Center has an active VA affiliation. The ESP 

Centers generate evidence syntheses on important clinical practice topics, and these reports help: 

• develop clinical policies informed by evidence, 

• guide the implementation of effective services to improve patient 

outcomes and to support VA clinical practice guidelines and 

performance measures, and 

• set the direction for future research to address gaps in clinical 

knowledge. 

In 2009, the ESP Coordinating Center was created to expand the capacity of QUERI Central 

Office and the four ESP sites by developing and maintaining program processes. In addition, 

the Center established a Steering Committee comprised of QUERI field-based investigators, 

VA Patient Care Services, Office of Quality and Performance, and Veterans Integrated Service 

Networks (VISN) Clinical Management Officers. The Steering Committee provides program 

oversight, guides strategic planning, coordinates dissemination activities, and develops 

collaborations with VA leadership to identify new ESP topics of importance to Veterans and the 

VA healthcare system. 

Comments on this evidence report are welcome and can be sent to Nicole Floyd, ESP 

Coordinating Center Program Manager, at nicole.floyd@va.gov. 

Recommended citation: Adam SS, McDuffie JR, Ortel TL, Nagi A, Williams JW Jr. Comparative 

Effectiveness of Warfarin and Newer Oral Anticoagulants for the Long-term Prevention and 

Treatment of Arterial and Venous Thromboembolism. VA-ESP Project #09-010; 2012. 

This report is based on research conducted by the Evidence-based Synthesis Program 

(ESP) Center located at the Durham VA Medical Center, Durham, NC, funded by the 

Department of Veterans Affairs, Veterans Health Administration, Office of Research and 

Development, Quality Enhancement Research Initiative. The findings and conclusions 

in this document are those of the author(s) who are responsible for its contents; the 

findings and conclusions do not necessarily represent the views of the Department 

of Veterans Affairs or the United States government. Therefore, no statement in this 

article should be construed as an official position of the Department of Veterans Affairs. 

Potential conflicts of interest: Dr. Ortel: Grants: GlaxoSmithKline, Eisai, Daichi Sankyo, 

Pfizer; Consultancy: Boehringer Ingelheim. No other investigators have any affiliations 

or financial involvement (e.g., employment, consultancies, honoraria, stock ownership or 

options, expert testimony, grants or patents received or pending, or royalties) that conflict 

with material presented in the report. 

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Warfarin and Newer Oral Anticoagulants: 


Long-term Prevention and Treatment of Arterial and VTE Evidence-based Synthesis Program
 

EXECUTIVE SUMMARY 

BACKGROUND 

Thromboembolic diseases represent a major public health burden and are associated with 

significant morbidity and mortality. For over 50 years, vitamin K antagonists (VKAs) have been 

the mainstay of treatment and prophylaxis of thromboembolism. There are many indications 

for VKA, including primary prevention of systemic embolism in nonvalvular atrial fibrillation 

(AF) and mechanical prosthetic heart valves. Other indications include secondary prophylaxis 

following venous thromboembolism (VTE) and preventing stroke in patients with a mural 

thrombus following myocardial infarction. 

In North America, warfarin is the most widely used VKA. In 2004, more than 30 million 

prescriptions for warfarin were written in the United States. Warfarin significantly reduces the 

risk for thromboembolic complications in AF, mechanical heart valves, and VTE. However, 

warfarin therapy has several disadvantages, including its narrow therapeutic window and wide 

interindividual and intraindividual variability in anticoagulant effect. This variability dictates 

the need for continuous and regular monitoring, using the international normalized ratio (INR), 

to maintain patients within the desired therapeutic range. Even with regular monitoring, 30 

to 50 percent of INR values fall outside the target range. Furthermore, patients find repeated 

venipuncture for INR monitoring tedious, and health care providers find it costly. 

Over the past decade, several novel oral anticoagulants have emerged. These anticoagulants 

fall under two drug classes: (1) factor Xa (FXa) inhibitors and (2) direct thrombin inhibitors 

(DTIs). These drugs characteristically have a predictable anticoagulant effect, eliminating the 

need for routine monitoring. Moreover they have a faster onset of action, and there is no need to 

overlap with a parenteral agent when starting thromboprophylaxis—as is the case with warfarin. 

Warfarin reversal is necessary in some cases of overanticoagulation, which can be achieved 

using specific products and according to established guidelines. Despite the shorter half-life of 

new oral anticoagulants compared with warfarin, there are well-founded concerns over the lack 

of specific antidotes to reverse their anticoagulant effect in a timely fashion in case of bleeding 

or in preparation for a procedure. These concerns are more pronounced in elderly patients and 

those with renal impairment. Furthermore, drug acquisition costs are much higher for the newer 

anticoagulants than for warfarin. 

This review was commissioned by the Evidence-based Synthesis Program of the Department of 

Veterans Affairs (VA) to evaluate newer anticoagulants compared with warfarin. The topic was 

nominated after a topic refinement process that included a preliminary review of published peerreviewed literature, consultation with internal partners and investigators, and consultation with 

key stakeholders. We further developed and refined the following key questions (KQs) based on 

the review of published peer-reviewed literature in consultation with VA and non-VA experts: 

Key Question 1. For patients with chronic nonvalvular AF, what is the comparative effectiveness 

of long-term anticoagulation using newer oral anticoagulants versus warfarin on stroke 

incidence, mortality, health-related quality of life (HRQOL), and patient treatment experience? 

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Warfarin and Newer Oral Anticoagulants: 


Long-term Prevention and Treatment of Arterial and VTE Evidence-based Synthesis Program
 

Key Question 2. For patients with venous thromboembolism, are there differential effects 

of newer oral anticoagulants versus warfarin or low molecular weight heparins on recurrent 

thromboembolism, mortality, HRQOL, and patient treatment experience? 

Key Question 3. For patients with mechanical heart valves, what is the comparative effectiveness 

of newer oral anticoagulants versus warfarin on the incidence of thromboembolic complications, 

mortality, HRQOL, and patient treatment experience? 

Key Question 4. When used for long-term anticoagulation treatment, what is the nature and 

frequency of adverse effects for newer oral anticoagulants versus warfarin? 

METHODS 

We searched MEDLINE® (via PubMed®), Embase®, and the Cochrane Library of Systematic 

Reviews for peer-reviewed publications comparing the newer oral anticoagulants to standard care 

(usually VKAs) from January 2001 (the year newer oral anticoagulants were introduced) through 

May 2011. Our search strategy used the National Library of Medicineís medical subject headings 

(MeSH) keyword nomenclature and text words for newer anticoagulants and the conditions of 

interest. Our final search terms included new or novel anticoagulants; direct thrombin inhibitors, 

including dabigatran, and ximelagatran; factor Xa inhibitors, including edoxaban, rivaroxaban, 

apixaban, betrixaban, YM150; and the names of the conditions of interestóatrial fibrillation, 

venous thromboembolism, and mechanical heart valve. We limited the search to articles involving 

human subjects 18 years of age and older and published in the English language. Based on the 

recommendations of our reviewers, we searched for observational studies that documented adverse 

effects and updated the original search through February 2012 via PubMed® only. We also searched 

the Food and Drug Administration (FDA) databases for documentation of adverse effects. We 

developed our search strategy in consultation with an experienced search librarian. To assess 

publication bias, we searched www.clinicaltrials.gov for completed but unpublished studies. 

DATA SYNTHESIS 

We critically analyzed studies to compare their characteristics, methods, and findings. We 

then determined the feasibility of completing a quantitative synthesis (i.e., meta-analysis) 

by exploring the volume of relevant literature, the completeness of the results reporting, and 

the conceptual homogeneity of the studies. When a meta-analysis was appropriate, we used 

random-effects models to synthesize the available evidence quantitatively. For three-arm studies 

that included more than one dose of the newer anticoagulant, we used data from the treatment 

arm using the standard FDA-approved dose. We conducted sensitivity analyses by including 

the studies that (1) evaluated ximelagatran, a newer anticoagulant (no longer available) and 

(2) used the other dose of the newer anticoagulant in three-arm studies. Heterogeneity was 

examined among the studies using graphical displays and test statistics (Cochran’s Q and I2

). 

The I2 describes the percentage of total variation across studies due to heterogeneity rather than 

to chance. Heterogeneity was categorized as low, moderate, or high based on I2

 values of 25 

percent, 50 percent, and 75 percent respectively. 

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Warfarin and Newer Oral Anticoagulants: 


Long-term Prevention and Treatment of Arterial and VTE Evidence-based Synthesis Program
 

The outcomes for this report were binary; therefore we summarized these outcomes by a 

weighted-effect measure for proportions (e.g., risk ratio). We present summary estimates and 95 

percent confidence intervals (CIs). When there were statistically significant treatment differences, 

we estimated the absolute treatment effect by calculating the risk difference. Risk difference was 

calculated using the median event rate from the control treatments and the summary risk ratio. 

For KQ 4 (adverse effects), analyses were compared for consistency across conditions, and a 

sensitivity analysis was performed to examine the effect of ximelagatran (withdrawn from the 

market due to liver toxicity). 

RATING THE BODY OF EVIDENCE 

In addition to rating the quality of individual studies, we evaluated the overall strength of 

evidence (SOE) for each KQ by assessing the following domains: risk of bias, consistency, 

directness, precision, strength of association (magnitude of effect), and publication bias. 

These domains were considered qualitatively, and a summary rating of high, moderate, low, or 

insufficient SOE was assigned after discussion by two reviewers. 

PEER REVIEW 

The draft version of the report was reviewed by technical experts and clinical leadership. A 

transcript of their comments is in an appendix of the full report, which elucidates how each 

comment was considered in the final report. 

RESULTS 

We identified 594 unique citations from a combined search of MEDLINE (via PubMed, n = 

338), Embase (n = 178), and the Cochrane Database of Systematic Reviews (n = 78). Manual 

searching of included study bibliographies and review articles identified an additional 17 

citations for a total of 611 citations. After applying inclusion/exclusion criteria at the title-andabstract level, 80 full-text articles were retrieved and screened. Of these, 56 were excluded at the 

full-text screening stage, leaving 24 articles (representing 8 unique studies) for data abstraction. 

All studies compared newer anticoagulants to adjusted-dose warfarin; there were no direct 

comparisons between newer anticoagulants. Our search of www.clinicaltrials.gov did not suggest 

publication bias. A separate search of the observational study literature yielded 369 references. 

Manual searches and reviewer suggestions added an additional 8 articles. After applying our 

eligibility criteria, 28 articles were retrieved and screened at the full-text level. Of these, 10 

articles (including 7 unique studies) were retained for data abstraction. 

Key Question 1. For patients with chronic nonvalvular AF, what is the comparative 

effectiveness of long-term anticoagulation using newer oral anticoagulants 

versus warfarin on stroke incidence, mortality, health-related quality of life 

(HRQOL), and patient treatment experience? 

Five good-quality studies, involving 57,908 patients compared newer anticoagulants (FXa, two 

studies; DTI, three studies) with adjusted-dose warfarin. The mean age of participants was over 70 

years; about 55 percent were men and CHADS2 scores averaged from 2.1 to 3.5. Key exclusion 

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Warfarin and Newer Oral Anticoagulants: 


Long-term Prevention and Treatment of Arterial and VTE Evidence-based Synthesis Program
 

criteria were marked renal impairment, aspirin use of more than 100 to 165 mg, uncontrolled 

hypertension, prior stroke, significant anemia, and platelet count lower than 90,000 to 100,000. In the 

control groups, the percentage of time in the INR target range was 55 to 68 percent (median 66%). 

Table ES-1 summarizes the findings and SOE for each major outcome. In brief, newer 

anticoagulants were associated with a lower rate of all-cause mortality compared with 

warfarin (high SOE). Newer anticoagulants were also associated with fewer hemorrhagic 

strokes (moderate SOE). For these outcomes, we estimated the absolute risk difference to be 8 

fewer deaths and 4 fewer hemorrhagic strokes for every 1000 patients treated with the newer 

anticoagulants compared with adjusted-dose warfarin over approximately 2 years of treatment. 

The difference in bleeding-related outcomes is dependent in part on the quality of adjusted-dose 

warfarin treatment; these studies reported rates of time in therapeutic range that were similar to 

those observed in the Veterans Health Administration (VHA). Except for discontinuations due 

to adverse effects, other outcomes also favored newer anticoagulants; however, they were not 

statistically significant. No studies reported effects on patient experience or HRQOL. 

In addition to these findings, we evaluated subgroup analyses from the primary trials. These 

analyses showed no differential effects on stroke prevention (interaction effects) for individuals 

with a history of cerebrovascular accidents, impaired renal function, or older age. However, these 

analyses suggest that some bleeding complications with dabigatran compared with warfarin may 

be increased in patients older than age 75 and at centers with high-quality warfarin treatment. 

The effects of impaired renal function were mixed, showing no interaction effect in one analysis 

and a differential risk of gastrointestinal bleeding with rivaroxaban in another analysis. 

Table ES-1. Summary of the strength of evidence for KQ 1—chronic AF 

Number 

of Studies 

(Subjects) 

Domains Pertaining to SOE SOE 

Risk of Bias: 

Study Design/ 

Quality 

Consistency Directness Precision Effect Estimate (95% CI) 

All-cause mortality High SOE 

3 (44,442) RCT/Good Consistent Direct Precise RR = 0.88 (0.82 to 0.95) 

RD = 8 (3 to 11) fewer 

deaths/1000 

VTE-related mortality Moderate SOE 

2 (30,299) RCT/Good Some 

inconsistency 

Direct Some 

imprecision 

RR = 0.77 (0.57 to 1.02) 

Ischemic stroke Moderate SOE 

3 (44,442) RCT/Good Consistent Direct Some 

imprecision 

RR = 0.89 (0.78 to 1.02) 

Hemorrhagic stroke Moderate SOE 

3 (44,442) RCT/Good Some 

inconsistency 

Direct Some 

imprecision 

RR = 0.46 (0.31 to 0.68) 

RD = 4 (2 to 5) fewer 

hemorrhagic strokes/1000 

Discontinuation due to adverse effects Low SOE 

3 (44,502) RCT/Good Important 

inconsistency 

Direct Important 

imprecision 

RR = 1.26 (0.86 to 1.84) 

Major bleeding Low SOE 

3 (44,474) RCT/Good Important 

inconsistency 

Direct Some 

imprecision 

RR = 0.88 (0.70 to 1.09) 

Abbreviations: CI = confidence interval; RCT = randomized controlled trial; RD = risk difference; RR = risk ratio; SOE = 

strength of evidence 

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Warfarin and Newer Oral Anticoagulants: 


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Key Question 2. For patients with venous thromboembolism, are there differential 

effects of newer oral anticoagulants versus warfarin or low molecular weight 

heparins on recurrent thromboembolism, mortality, HRQOL, and patient treatment 

experience? 

Three good-quality studies, involving 8,477 patients compared newer anticoagulants (FXa, one 

study; DTI, two studies) to adjusted-dose warfarin. The average age of participants was 50 to 55 

years; about 56 percent were men. Key exclusion criteria were marked renal impairment and, 

less commonly, prior stroke or low platelet count. In the control groups, the percentage of time in 

the INR target range was 58 to 61 percent (median 60%). 

Table ES-2 summarizes the findings and SOE for each major outcome. In comparison with the 

chronic AF studies, there were fewer studies and patients enrolled as well as shorter duration of 

followup for this population. The summary risk ratio favored newer anticoagulants for all-cause 

mortality, VTE-related mortality, recurrent VTE, and major bleeding, but in each instance the CI 

included no effect. Overall, these results support the conclusion that newer anticoagulants are no 

worse than adjusted-dose warfarin for major clinical outcomes. No studies reported effects on 

patient experience or HRQOL. 

Table ES-2. Summary of the strength of evidence for KQ 2—venous thromboembolism 

Number 

of Studies 

(Subjects) 

Domains Pertaining to SOE SOE 

Risk of Bias: 

Study Design/ 

Quality 

Consistency Directness Precision Effect Estimate (95% CI) 

All-cause mortality Moderate SOE 

2 (5988) RCT/Good Consistent Direct Some 

imprecision 

RR = 0.83 (0.59 to 1.18) 

VTE-related mortality Low SOE 

2 (5988) RCT/Good Consistent Direct Important 

imprecision 

RR = 0.56 (0.19 to 1.69) 

Recurrent DVT/PE Moderate SOE 

2 (5988) RCT/Good Some 

inconsistency 

Direct Some 

imprecision 

RR = 0.85 (0.54 to 1.33) 

Discontinuation due to adverse effects Moderate SOE 

2 (5988) RCT/Good Consistent Direct Some 

imprecision 

RR = 1.19 (0.93 to 1.51) 

Major bleeding Moderate SOE 

2 (5988) RCT/Good Consistent Direct Some 

imprecision 

RR = 0.77 (0.49 to 1.20) 

Abbreviations: CI = confidence interval; NA = not applicable; NR = not reported; RCT = randomized controlled trial; RR = risk 

ratio; SOE = strength of evidence 

Key Question 3. For patients with mechanical heart valves, what is the 

comparative effectiveness of newer oral anticoagulants versus warfarin on the 

incidence of thromboembolic complications, mortality, HRQOL, and patient 

treatment experience? 

We did not identify any published studies that compared newer anticoagulants to adjusted-dose 

warfarin in patients with mechanical heart valves. We identified one ongoing, Phase II trial of 

dabigatran from our search of www.clinicaltrials.gov. 

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Warfarin and Newer Oral Anticoagulants: 


Long-term Prevention and Treatment of Arterial and VTE Evidence-based Synthesis Program
 

Key Question 4. When used for long-term anticoagulation treatment, what is the 

nature and frequency of adverse effects for newer oral anticoagulants versus 

warfarin? 

The adverse effects of newer oral anticoagulants compared with adjusted-dose warfarin were 

generally consistent across treatment indications. After excluding the ximelagatran studies, the 

summary risk ratio for discontinuation due to adverse effects was higher for newer anticoagulants, 

but this result was not statistically significant. The effects on bleeding rates are complex. Fatal 

bleeding was significantly lower for newer oral anticoagulants, an effect that was consistent across 

drug classes. Major bleeding was lower for newer oral anticoagulants, but this effect was not 

statistically significant and varied greatly across studies. In contrast, gastrointestinal bleeding was 

increased with newer oral anticoagulants. Gastrointestinal bleeding was significantly increased in 

patients treated with dabigatran and rivaroxaban compared with warfarin. The efflux of dabigatran 

by p-glycoprotein transporters into the gastrointestinal tract may be a mechanism for this finding. 

Subgroup analyses from clinical trials and FDA reports suggest that bleeding risk may be increased 

in older adults and in those with impaired renal function. Further, the differential bleeding risk may 

be related to the quality of warfarin anticoagulation. 

Another potential adverse effect is myocardial infarction. We found no increased risk when 

combining results from all studies. However, for dabigatran alone, we found an elevated risk 

(RR = 1.35) that approached statistical significance. A separate meta-analysis, primarily of shortterm trials, found a statistically significant increase in myocardial infarction or acute coronary 

syndrome (OR 1.33; 95% CI, 1.03 to 1.71). Liver dysfunction was substantially higher for 

ximelagatran, a drug withdrawn from the market due to this adverse effect. Elevated rates of 

liver dysfunction have not been seen with the other newer oral anticoagulants. The SOE was 

low for several outcomes because CIs included clinically important differences, and there was 

unexplained variability in treatment effects (Table ES-3). 

Table ES-3. Summary of findings for KQ 4—adverse effects 

Outcome Strength of 

Evidence Summary 

Drug 

discontinuation 

due to adverse 

effects 

Low 

Across all indications, discontinuation due to adverse effects was higher 

with newer oral anticoagulants (RR 1.23; 95% CI, 0.94 to 1.61), but the 

95-percent CI was large and included no effect. In subgroup analysis, rates 

of discontinuation were higher for dabigatran compared with FXa inhibitors. 

A clinically important increase in drug discontinuation compared with 

warfarin cannot be excluded. 

Major bleeding 

Fatal bleeding 

Low 

Moderate 

Across all indications, the risk of major bleeding was lower with newer 

oral anticoagulants (RR 0.86; 95% CI, 0.71 to 1.04), but the 95-percent CI 

was large and included no effect. A clinically important decrease in major 

bleeding compared with warfarin cannot be excluded. In December 2011, 

the FDA issued a notice that it was evaluating reports of serious bleeding 

with dabigatran. 

Across all indications, the risk of fatal bleeding was lower with newer oral 

anticoagulants (RR 0.59; 95% CI, 0.46 to 0.77). Risk difference was 1 

fewer death per 1000 patients. 

Gastrointestinal 

bleeding Moderate 

Across all indications, the risk of gastrointestinal bleeding was increased 

with newer oral anticoagulants (RR 1.30; 95% CI, 1.17 to 1.49). Risk 

difference was 1 additional gastrointestinal bleed per 1000 patients. 

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Warfarin and Newer Oral Anticoagulants: 


Long-term Prevention and Treatment of Arterial and VTE Evidence-based Synthesis Program
 

Outcome Strength of 

Evidence Summary 

Myocardial 

infarction Low 

Across all indications, the risk of myocardial infarction was not different with 

newer oral anticoagulants (RR 1.02; 95% CI, 0.76 to 1.39). In a subgroup 

analysis, the risk was increased with dabigatran (RR 1.35; CI, 0.99 to 

1.85) compared with FXa inhibitors (RR 0.86; CI, 0.66 to 1.11); p = 0.03 for 

between-group comparison. 

Liver dysfunction Moderate 

Across all indications, the risk of liver dysfunction was not different with 

newer oral anticoagulants (RR 0.82; 95% CI, 0.61 to 1.11). 

RECOMMENDATIONS FOR FUTURE RESEARCH 

We used a structured framework to identify gaps in evidence and classify why these gaps exist 

(Table ES-4). 

Table ES-4. Evidence gaps and future research 

Evidence Gap Reason Type of Studies to Consider 

Absence of data for patients with 

mechanical heart valves Insufficient information Multicenter RCTs 

Uncertain effects on patient experience 

and health-related quality of life Insufficient information Multicenter RCTs and/or qualitative studies 

Uncertain relative benefits across and 

within newer anticoagulant drug classes Insufficient information 

Multicenter RCTs comparing newer 

anticoagulants to each other and network 

meta-analyses 

Uncertain effects on health system costs Insufficient information Budget impact analysis 

Effects on thrombosis and systemic 

embolism when newer anticoagulants are 

stopped prior to invasive procedures 

Insufficient information Pharmacokinetic studies; observational 

studies 

Management of patients on newer 

anticoagulants with bleeding complications Insufficient information RCTs; observational studies 

Adverse effects with long-term use and in 

usual clinical practice Insufficient information Observational studies 

Abbreviation: RCT = randomized controlled trial 

CONCLUSION 

Our review shows that the newer oral anticoagulants are a viable option for longterm anticoagulation. DTIs and FXa inhibitors have the advantage of more predictable 

anticoagulation, fewer drugñdrug interactions, and equivalent or better mortality and vascular 

outcomes compared with warfarin. However, the treatment benefits compared with warfarin 

are small and vary depending on the quality of warfarin anticoagulation. Also, no studies have 

evaluated these drugs in patients with mechanical heart valves, the drugs are costly, and the FDA 

is evaluating numerous reports of bleeding complications, particularly in older adults and those 

with severely impaired renal function. Because there are no head-to-head comparisons of newer 

anticoagulants, we were unable to determine if effects varied across drugs, and we had limited 

ability to test for differences between DTI and FXa drug classes. 

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CI 

Warfarin and Newer Oral Anticoagulants: 

Long-term Prevention and Treatment of Arterial and VTE Evidence-based Synthesis Program 

ABBREVIATIONS TABLE 

AF	 atrial fibrillation 

confidence interval 

FDA U.S. Food and Drug Administration 

FXa factor Xa inhibitor 

HRQOL health-related quality of life 

INR international normalized ratio 

KQ key question 

MeSH medical subject headings 

NA not applicable 

NR not reported 

RCT randomized controlled trial 

RD risk difference 

RR risk ratio 

SOE strength of evidence 

VA Department of Veterans Affairs 

VHA Veterans Health Administration 

VKA vitamin K antagonist 

VTE venous thromboembolism 

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