Systematic literature review of treatment patterns for venous thromboembolism patients during transitions from inpatient to post-discharge settings

Figures & data

Figure 1 Clinical search results.

Abbreviations: Conf, conference; DVT, deep vein thrombosis; IP, inpatient; NOAC, new/novel oral anticoagulant; PE, pulmonary embolism; tx, treatment; VKA, vitamin K antagonist; VTE, venous thromboembolism; wo, without.

Figure 2 Economic search results.

Abbreviations: Conf, conference; DVT, deep vein thrombosis; IP, inpatient; NOAC, new/novel oral anticoagulant; PE, pulmonary embolism; tx, treatment; VKA, vitamin K antagonist; VTE, venous thromboembolism; wo, without.

Table 1 Study characteristics

Characteristics	All studies (n=49)	Clinical studies (n=24)	Economic studies (n=25)
Patient demographics
Mean age (years), range	47.0–69.2	47.0–68.7	47.2–69.2
% Male, range	33.8–61.5	40.0–61.5	33.8–58.8
Populations reported, n (%)
VTE	13 (26.5)	4 (8.2)	9 (18.4)
DVT only	9 (18.4)	7 (14.3)	2 (4.1)
PE only	11 (22.4)	4 (8.2)	7 (14.3)
DVT+PE combination	14 (28.6)	9 (18.4)	5 (10.2)
VTE+atrial fibrillation	2 (4.1)	–	2 (4.1)
Discharge location reported, n (%)
Studies reporting discharge	11 (22.4)	7 (29.2)	4 (16.0)
Home	6 (12.2)	5 (10.2)	1 (2.0)
Home or skilled nursing	3 (6.1)	–	3 (6.1)
OP (nonspecified)	3 (6.1)	2 (4.1)	1 (2.0)
IP-only study	17 (34.7)	7 (14.3)	10 (20.4)
Not reported	21 (40.8)	10 (20.4)	11 (20.4)

Note: Studies may report more than one type of discharge location.

Abbreviations: DVT, deep vein thrombosis; IP, inpatient; OP, outpatient; PE, pulmonary embolism; VTE, venous thromboembolism.

Table 2 Number of studies reporting treatments and outcomes

Characteristics	All studies (n=49)	Clinical studies (n=24)	Economic studies (n=25)
Treatments reported (n)
IP DOAC	27	14	13
IP VKA	25	13	12
IP IAC	22	12	10
IP treatment not reported	15	5	10
OP DOAC	13	8	5
OP VKA	16	11	5
OP IAC	9	5	4
OP treatment not reported	26	12	14
Reported both IP and OP treatment	11	8	3
Outcomes reported (n)
Hospital length of stay	25	11	14
Time to discharge	7	5	2
Readmission	12	5	7
Treatment response	8	8	–
Complications	17	8	9
Treatment discontinuation	4	4	–
Mortality	19	8	11
Treatment adherence	6	6	–
Health care resource utilization	22	12	10
Health care costs	28	3	25

Note: Studies may report more than one type of treatment and/or outcome.

Abbreviations: DOAC, direct oral anticoagulant; IAC, indirect or injectable anticoagulant; IP, inpatient; OP, outpatient; VKA, vitamin K antagonist.

Table 3 Clinical studies

Study design/data source/study period	Patient population and setting	Outcomes reported in study	Treatments	Treatment patterns and transition of care results	NICE quality assessment	Comments
Bashir and coworkers (2015)^Citation58 Retrospective claims analysis/NIS files of the AHRQ Healthcare Cost and Utilization Project/January 2005–December 2010	DVT, n=90,618; anticoagulant+CDT, n=3,649; anticoagulant alone, n=86,969; IP	Hospital LOS, complications, mortality, resource utilization, cost findings	IP: unspecified anticoagulants; OP: not reported (IP-only study)	4.1% underwent CDT in addition to anticoagulant therapy. Compared with anticoagulant therapy only, CDT was associated with higher rates of blood transfusion, PE, hemorrhage, vena cava filter placement, but not mortality. CDT patients had longer LOS and higher hospital costs	Low risk for selection, attrition, and detection bias	Discharge location not reported; sensitivity analyses indicated that differences were not likely to be due to an unmeasured confounder
Beam et al (2015)^Citation20
Prospective observational study/ED medical data/March 25, 2013–April 30, 2014	DVT or PE, n=106; DVT, n=71; PE, n=30; DVT+PE, n=5; IP and OP	Readmission, Tx response, complications, discontinuation, mortality, Tx adherence, resource utilization	IP: enoxaparin, rivaroxaban; OP: rivaroxaban	Patients followed up for a mean of 389 days. No VTE recurrence or major bleeding event while on therapy; 3 patients had recurrent DVT after therapy cessation	Risk NA for selection bias; unclear risk for attrition bias, low risk for detection bias	Discharged home
Cai et al (2014)^Citation26
Retrospective claims analysis/Truven Health MarketScan Database/January 1, 2010–December 31, 2011	VTE, n=5,820; parenteral anticoagulant users, n=4,403; parenteral anticoagulant nonusers, n=1,417; OP	Tx response	IP: not reported; OP: warfarin	76.0% of those receiving warfarin also received an IAC. Median time from VTE diagnosis to warfarin initiation was shorter for IAC users than nonusers (5 vs 11 days)	Risk NA for selection and attrition bias; low risk for detection bias	OP-only study; discharge location not reported
Cefalo et al (2015)^Citation23
Retrospective and prospective/tertiary referral hospital/October 2008–December 2011 and May 2005–April 2008	PE, n=547; prospective cohort, n=298; retrospective cohort, n=249; IP and OP	Complications, mortality, resource utilization	IP: IV UH or LMWH; OP: warfarin	Compared with those younger than 65 years, patients aged 65+ years had more severe PE and higher 30-day mortality (11.0% vs 3.0%, P<0.001). Tx patterns were similar between the two age groups	Risk NA for selection and attrition bias; low risk for detection bias	Discharged to unspecified OP location. Patients aged 65+ years were most likely to present with submassive PE, whereas patients younger than 65 years were most likely to present with low-risk PE
Chen et al (2013)^Citation59
Retrospective claims analysis/Thomson Reuters MarketScan database/January 1, 2006–March 31, 2008	VTE, n=8,040; IP and OP	Tx response, discontinuation, Tx adherence	IP: not reported; OP: warfarin	Among those with 2+ warfarin prescriptions, 34.0% were not compliant with warfarin therapy; noncompliance and discontinuation associated with higher likelihood of recurrent VTE	Unclear risk for selection bias, risk NA for attrition bias; low risk for detection bias	Discharge location not reported; association between Tx adherence and recurrent VTE remained in sensitivity analysis
Deitelzweig et al (2016)^Citation28
Retrospective matched cohort/MarketScan Hospital Drug Database/November 2012–December 2013 (conf abstract)	DVT or PE, n=2,446; DVT, n=472; PE, n=751 in each rivaroxaban and warfarin group; IP	Hospital LOS, time to discharge	IP: warfarin, rivaroxaban; OP: not reported	Hospital LOS shorter for rivaroxaban (3.7 days) vs warfarin (5.2 days, P<0.001). Time to discharge also shorter for rivaroxaban vs warfarin (2.4 vs 3.9 days, P<0.001)	Low risk for selection and detection bias; risk NA for attrition bias	Discharge location not reported
Deitelzweig et al (2016)^Citation27
Retrospective matched cohort/Truven Health Analytics MarketScan databases/January 2011–December 2013	DVT, n=2,161 in nonmatched cohort (n=512 in rivaroxaban and 1,649 in LMWH/warfarin groups); n=1,024 in matched cohort (n=512 in each tx group); OP	Resource utilization, cost findings	IP: not reported; OP: warfarin, rivaroxaban (OP only study)	Compared with those on warfarin, those on rivaroxaban had fewer all-cause and VTE-related hospitalizations and OP during the first 4 weeks after the initial encounter (no difference in ED visits). Mean costs were also lower for rivaroxaban users during this time period	Low risk for selection and detection bias; risk NA for attrition bias	OP-only study; results were similar in sensitivity analyses that extended the observation period until the end of data availability or insurance coverage
Deitelzweig et al (2015)^Citation29
Retrospective matched cohort/MarketScan Hospital Drug Database/November 1, 2012–December 31, 2013 (conf abstract)	DVT or PE, n=2,446; DVT, n=472; PE, n=751 in each rivaroxaban and warfarin group; IP	Hospital LOS, time to discharge	IP: warfarin, rivaroxaban; OP: not reported	Hospital LOS was significantly shorter on rivaroxaban vs warfarin for both DVT (3.7 vs 5.0 days, P<0.001) and PE (3.8 vs 5.0 days, P<0.001); days to discharge was also significantly shorter for rivaroxaban, regardless of whether patients initiated with IACs	Low risk for selection and detection bias; risk NA for attrition bias	Discharge location not reported
Desai et al (2016)^Citation18
Retrospective observational cohort/hospital medical records/January 2011–July 2014	VTE, n=414; discharged on rivaroxaban, n=72; discharged on warfarin, n=203; discharged on warfarin and enoxaparin, n=89; discharged on enoxaparin, n=50; IP and OP	Hospital LOS, readmission, complications	IP: warfarin, enoxaparin, rivaroxaban; OP: same	Patients discharged on rivaroxaban had significantly shorter LOS (3.5 days) than those discharged on warfarin (7.0 days, P<0.001), but not compared with those discharged on enoxaparin alone (3.0 days) or enoxaparin+warfarin (4.0 days). Bleeding and readmission rates were not significantly different	Unclear risk for selection bias, low risk for attrition and detection bias	Discharge location not reported
Falconieri et al (2014)^Citation21
Retrospective/Wellsoft system using hospital data/October 2013–March 2014	DVT, n=32; discharged from ED pre-FAST, n=8; discharged from ED post-FAST, n=7; admitted pre-FAST, n=9; admitted post-FAST, n=8; ED and OP	Readmission, complications, Tx adherence, resource utilization	ED: warfarin, enoxaparin, rivaroxaban; OP: same (discharged from ED)	A transition of care program resulted in 100.0% of patients attending a follow-up appointment (mean time until appointment =4.4 days). Patient satisfaction with the program was high	Unclear risk for selection bias, risk NA for attrition bias; low risk for detection bias	None of the patients at the 3- to 5-day follow-up phone call and 30-day phone call had any issues taking their anticoagulant, and none reported side effects of significant bleeding. One patient was re-admitted after discharge with a pulmonary embolism
Fang et al (2013)^Citation60
Retrospective/electronic databases from 4 healthcare delivery systems/January 1, 2004–December 31, 2010 (conf abstract)	PE, n=5,600; IP and OP	Mortality	IP: not reported; OP: warfarin	After adjustment, lower times within therapeutic range (INR) were associated with higher mortality. Compared with time in therapeutic range >70.0%, adjusted death HRs were: 3.8 for those 40.0%–49.0% and 8.0 for those <40.0%	Risk NA for selection and attrition bias; low risk for detection bias	Discharged to unspecified OP location; the mean time in therapeutic range was 49.1%
Jean et al (2017)^Citation61
Retrospective chart review/hospital chart review/January 1, 2009–December 31, 2014	DVT or PE, n=457; DVT, n=220; PE, n=181; DVT+PE, n=56; IP	Tx response, mortality, Tx adherence	IP: enoxaparin, dalteparin, fondaparinux, warfarin, rivaroxaban; OP: not reported	Recurrent VTE in 5.0% of patients (no difference between oral and IACs), medication compliance issue in 5 patients of IAC group and 0 of oral group (P=0.008); 4 thrombotic events and 1 bleeding event listed as contributory diagnoses on the IP death summary	Risk NA for selection and attrition bias; low risk for detection bias	Discharge location not reported
Levy et al (2011)^Citation62
Retrospective observational cohort/Medical center database/April 2005–Jul 2007	DVT, n=200; anticoagulation, n=73; no anticoagulation, n=127; IP	Tx response, complications, mortality, resource utilization	IP: fractionated or UH, warfarin; OP: not reported	36.0% of patients with upper extremity DVT were put on anticoagulation therapy. Younger age, duplex evidence of an acute DVT, and involvement of multiple upper extremity segments were predictive of therapy initiation	Risk NA for selection and attrition bias; low risk for detection bias	Discharge location not reported; Two patients (1.0%) suffered PE, 2 other patients treated with warfarin died months after discharge from intracranial bleedings after minor falls
Liu et al (2013)^Citation63
Retrospective/Truven Health MarketScan database/Jul 1, 2006–December 31, 2011 (conf abstract)	DVT and PE, n=153,908; IP	Discontinuation	IP: warfarin; OP: not reported	Mean therapy duration was 5 months; 74.8% discontinued within 1 year. Less likely to discontinue: if age >40 years, PE (vs DVT), atrial fibrillation. More likely to discontinue: if history of pregnancy, fracture, alcohol/drug use, hormone therapy, and major bleeding in prior 6 months	Unclear risk for selection bias, risk NA for attrition bias; low risk for detection bias	Discharge location not reported
Menzin et al (2014)^Citation24
Retrospective/Humedica database/January 1, 2008–August 30, 2012	DVT and PE, n=2,060; DVT, n=864; PE, n=687; DVT+PE, n=509; IP and OP	Hospital LOS, readmission, Tx response, complications, mortality, resource utilization	IP: heparin, warfarin; OP: not reported	Heparin+warfarin had shorter mean LOS, fewer used ICU/CCU, fewer with major bleeding, lower in-hospital mortality vs heparin alone; LOS longer for patients with DVT+PE (vs DVT alone) and patients aged >65 years; hospitalization for VTE recurrence: 7.5% at 1 year	Unclear risk for selection bias, risk NA for attrition bias; low risk for detection bias	Discharged to home or skilled nursing facility
Merli et al (2015)^Citation30
Retrospective matched cohort/Truven MarketScan Hospital Drug Database/January 2011–December 2013	DVT; unmatched: current rivaroxaban, n=134; current LMWH/warfarin, n=1,781; historical LMWH/warfarin, n=6,347 matched; current rivaroxaban, n=134; historical LMWH/warfarin, n=536; IP	Hospital LOS, readmission, resource utilization	IP: LMWH, warfarin, rivaroxaban; OP: not reported (IP-only study)	60.0% of rivaroxaban patients were admitted to the hospital vs 82.0% of historical matched LMWH/warfarin patients. Mean LOS was 2.6 days (rivaroxaban) vs 3.8 days	Low risk for selection bias and detection bias; risk NA for attrition bias	Discharge location not reported; admission rates adjusted for time-trend produced similar results
Roberts et al (2015)^Citation31
Retrospective observational cohort/hospital EMR/January 1, 2012–March 1, 2015	PE, n=158; warfarin+enoxaparin, n=82; rivaroxaban, n=76; IP	Hospital LOS, time to discharge	IP: warfarin, enoxaparin, rivaroxaban; OP: not reported	Median LOS was shorter for rivaroxaban patients (1.8 days) than for warfarin patients (2.7 days, P<0.001), as was the time to discharge (P<0.001)	Risk NA for selection and attrition bias; low risk for detection bias	Discharge location not reported; there were differences in baseline characteristics between Tx arms
Sharifi et al (2015)^Citation16
Retrospective and prospective/not reported/September 2011–June 2013	DVT, n = 127; IP and OP	Hospital LOS, Tx response, complications, mortality, Tx adherence	IP: dabigatran, rivaroxaban, apixaban; OP: warfarin, dabigatran, rivaroxaban, apixaban	Mean LOS was 46 hours; no occurrences of PE, 2 patients with recurrent DVT (both switched to warfarin); 4 deaths not related to DVT; postthrombotic syndrome developed in 5 patients (3.0%), 2 of whom had been switched to warfarin	Risk NA for selection and attrition bias; low risk for detection bias	Discharge location not reported; mean follow-up was 22 months; compliance with compression stockings was low
Spyropoulos et al (2017)^Citation19
Retrospective claims analysis/IMS PharMetrics Plus database/January 1, 2008–March 31, 2014	DVT, PE, or both, n=81,827; ACCP-recommended Tx duration adherent, n=60,550; nonadherent, n=21,277; IP and OP	Hospital LOS, Tx adherence, resource utilization, cost findings	IP: warfarin, rivaroxaban, dabigatran, apixaban; OP: same	74.0% were adherent to the ACCP-recommended Tx duration. Hospitalizations, VTE recurrence, bleeding events, and costs were lower among adherent patients	Risk NA for selection and attrition bias; low risk for detection bias	Discharge location not reported
Stein et al (2015)^Citation25
Retrospective/manual review of medical records/January 2013–December 2014	DVT, n=96; admitted from ED, n=85; discharged from ED to home, n=11; IP and OP	Hospital LOS, time to discharge, resource utilization	IP: warfarin, enoxaparin, rivaroxaban; OP: not reported	88.5% hospitalized and 11.5% discharged from ED to home. 9 of 11 discharged home received LMWH, none received DOACs. 33.0% of hospitalized patients discharged in ≤2 days, 64.0% of these received enoxaparin and/or warfarin at discharge, 25.0% rivaroxaban	Risk NA for selection and attrition bias; low risk for detection bias	Discharged home (no other information reported)
Stein et al (2016)^Citation22
Retrospective cohort study/medical records/January 2013–December 2014	PE, n=746; hospitalized, n=733; discharged to home, n=13; IP and OP	Hospital LOS, time to discharge, resource utilization	IP: LMWH, warfarin, DOAC; OP: same	16.2% were discharged within 2 days, and 1.7% (n=13) were discharged home. For the 13 home-treated patients, 9 received LMWH or warfarin, 4 received DOACs	Unclear risk for selection bias; risk NA for attrition and detection bias	1.7% discharged home, discharge location of remaining patients not reported
Streiff et al (2016)^Citation17
Retrospective claims analysis/Humana database/January 1, 2013–May 31, 2015 (conf abstract)	VTE, n=2,428; rivaroxaban, n=707; LMWH, n=660; warfarin, n=1,061; setting not specified	Tx response	IP: LMWH, warfarin, rivaroxaban; OP: same as IP	VTE recurrence for rivaroxaban users was 28.0% less likely than for those using LMWH and 26.0% less likely than for warfarin users	Unclear risk for selection and attrition bias, low risk for detection bias	Discharge location not reported; median duration on initial LMWH, warfarin, and rivaroxaban was 1.0, 3.5, and 3.0 months, respectively
Sussman et al (2015)^Citation64
Retrospective claims analysis/hospital claims data/November 1, 2011–December 31, 2013 (conf abstract)	DVT and/or PE, n=46,214; IP	Resource utilization	IP: LMWH, fondaparinux, UH, rivaroxaban; OP: not reported (IP-only study)	Use of IACs (with or without warfarin) were more common than the use of DOACs (rivaroxaban); of the roughly 11.0% who received rivaroxaban, >90.0% also received an IAC	Risk NA for selection and attrition bias; low risk for detection bias	Discharge location not reported
Xie et al (2016)^Citation65
Retrospective claims analysis/MarketScan database/January 2006–December 2011	DVT and PE, n=21,163; IP	Discontinuation	IP: warfarin; OP: not reported	21.4% discontinued with 3 months, 42.8% within 6 months, and 70.1% within 12 months. Reduced risk of discontinuation: PE (vs DVT), comorbid atrial fibrillation, thrombophilia, older age; increased risk of discontinuation: alcohol abuse, cancer history, bleeding, and catheter ablation	Unclear risk for selection bias, risk NA for attrition bias; low risk for detection bias	Discharge location not reported

Abbreviations: ACCP, American College of Chest Physicians; AHRQ, Agency for Healthcare Research and Quality; CCU, critical care unit; CDT, catheter-directed thrombectomy; conf, conference; DOAC, direct oral anticoagulant; DVT, deep vein thrombosis; ED, emergency department; EMR, electronic medical record; FAST, facilitating anticoagulation for safer transitions; IAC, indirect/injectable anticoagulant; ICU, intensive care unit; IMS, information management system; INR, international normalized ratio; IP, inpatient; IV, intravenous; LMWH, low-molecular-weight heparin; LOS, length of stay; NA, not applicable; NICE, National Institute for Health and Clinical Excellence; NIS, National Inpatient Sample; OP, outpatient; PE, pulmonary embolism; Tx, treatment; UH, unfractionated heparin; VTE, venous thromboembolism.

Table 4 Economic studies

Study design/data source/study period	Patient population and setting	Outcomes reported in study	Treatments	Transition of care results	CHEERS quality assessment deficient items	Comments
Amin et al (2015)^Citation54
Simulation/published data/2014–2018 (conf abstract)	VTE, n=1 million (hypothetical); IP and OP	Cost findings	IP: not reported; OP (see comments): dabigatran, rivaroxaban, apixaban, edoxaban, warfarin	Reduction in simulated direct costs for treated patients vs warfarin: apixaban ($11.5 M), edoxaban ($6.6 M), rivaroxaban ($4.2 M), dabigatran ($3.7 M)	3, 4, 5, 6, 8, 9, 13b, 14, 15, 16, 17, 20b	Discharge location not reported. The analysis was based on the published clinical trial data and did not report an OP setting, but is assumed to focus on costs of OP tx because of the timeframe used (1+ years)
Amin et al (2015)^Citation42
Retrospective claims analysis/Truven Health Analytics Commercial and Medicare MarketScan databases/January 1, 2008–December 31, 2011	VTE, n=112,885; n=15,897, major bleeding; n=15,842, nonmajor clinically relevant bleeding; n=81,146, no bleeding; IP and OP	Hospital LOS, resource utilization, complications, cost findings	IP and OP: not reported	Compared with patients without bleeding, patients with major bleeding (14.0%) had an average of $45,367 additional direct medical costs, and patient with clinically relevant nonmajor bleeding (14.0%) had an average of $2,140 additional direct costs	1, 9	Discharge location not reported
Amin et al (2016)^Citation50
Simulation/published data/January 1, 2008–December 31, 2011	VTE; n=not reported; IP and OP	Complications, mortality, cost findings	IP: not reported; OP (see comments): dabigatran, rivaroxaban, apixaban, edoxaban warfarin	Annual total medical cost avoidances per patient year (vs warfarin) were: –$4,440 for apixaban, –$2,971 for rivaroxaban, –$1957 for edoxaban, and –$572 for dabigatran	9, 13b, 15, 16, 20b	Discharge location not reported; results remained consistent under sensitivity analyses The analysis was based on the published clinical trial data and did not report an OP setting, but is assumed to focus on costs of OP tx because of the timeframe used (1+ years)
Amin et al (2015)^Citation51
Economic analysis/published data/2014–2018	VTE, n=1 million (hypothetical); IP and OP	Cost findings	IP: not reported; OP (see comments): dabigatran, rivaroxaban, apixaban, edoxaban warfarin	Annual medical cost differences associated with DOACs vs warfarin were estimated to be: –$204 for dabigatran, –$140 for rivaroxaban, –$495 for apixaban, –$340 for edoxaban	4, 9, 15, 16	Discharge location not reported The analysis was based on published clinical trial data and did not report an OP setting, but is assumed to focus on costs of OP tx because of the timeframe used (1+ years)
Amin et al (2015)^Citation56
Cost-avoidance analysis/published data/“extended treatment”	VTE, n=2,936; dabigatran (n=681)/rivaroxaban (n=602)/apixaban 2.5 mg (n=840)/apixaban 5 mg (n=813); IP and OP	Complications, mortality, cost findings	IP: not reported; OP (see comments): dabigatran, rivaroxaban, apixaban vs placebo	Because of reduction in VTE recurrence vs placebo, overall medical costs avoided were: –$2,794 for dabigatran, –$2,948 for rivaroxaban, –$4,249 for apixaban 2.5 mg and –$4,244 for apixaban 5 mg	9, 13b, 14, 15, 16, 20b	Discharge location not reported; sensitivity analyses indicated that estimated cost avoidances are robust to random variations The analysis was based on the published clinical trial data and did not report an OP setting, but is assumed to focus on costs of OP tx because of the timeframe used (1+ years)
Amin et al (2014)^Citation55
Cost analysis/published data/1-year timeframe	VTE; n=not reported; IP and OP	Complications, mortality, cost findings	IP: not reported; OP (see comments): dabigatran, rivaroxaban, apixaban, edoxaban, warfarin	All DOACs associated with lower rate of bleeding and recurrent VTE/death (except for dabigatran) vs standard therapy; as a result, annual total medical cost differences were: –$146 for dabigatran, –$482 for rivaroxaban, –$918 for apixaban, and –$344 for edoxaban	9, 15	Discharge location not reported; in an alternative scenario analysis when Tx durations were normalized, all DOACs still produced cost reductions The analysis was based on the published clinical trial data and did not report an OP setting, but is assumed to focus on costs of OP tx because of the timeframe used (1 year)
Atay et al (2012)^Citation49
Retrospective/published data/1-year timeframe	VTE, n=1,774; AF, n=1,256; VTE, n=518; IP	Cost findings	IP: dabigatran, warfarin; OP: not reported (IP-only study)	Annual cost of coagulation management: $4,371,136 for dabigatran vs $1,385,494 for warfarin. Note: while dabigatran’s cost was all due to the medication, the majority of the cost for warfarin was for lab and labor costs to monitor lab values	4, 9, 11b, 14, 17, 18	Discharge location not reported
Bookhart et al (2014)^Citation44
Post hoc analysis clinical trial data/not reported	DVT or PE, n=812; DVT, n=326; PE, n=486; IP	Hospital LOS, resource utilization, cost findings	IP: rivaroxaban, enoxaparin, unspecified VKA; OP: not reported (IP-only study)	47.0% rivaroxaban and 48.0% enoxaparin/VKA hospitalized; rivaroxaban had shorter LOS (1.6 days), $3,419 lower total costs	6, 8, 9, 17, 20a	Discharge location not reported; the authors note that Canadian centers tend to hospitalize few patients for DVT, so results are largely based on PE patients
Coleman et al (2017)^Citation52
Retrospective (longitudinal) claims analysis/Truven Health MarketScan Commercial Claims and Encounters Database/November 2011–July 2015	DVT or PE, n=32,787; rivaroxaban, n=10,929; warfarin, n=21,858; IP and OP	Cost findings	IP: not reported; OP: rivaroxaban, warfarin	During 12 month follow-up, rivaroxaban patients (vs warfarin) had lower IP (–$622) and OP (–$1,156) per patient costs, higher pharmacy costs ($661), and lower total costs (–$1,116)	6, 9	Discharge location not reported; Subgroup analyses: similar results when limited to DVT, no significant difference in total costs for PE
Coleman et al (2017)^Citation38
Retrospective claims analysis/Premier Perspective Comparative Hospital Database/November 2012–March 2015	PE, n=6,932 (1:1 matched cohort rivaroxaban vs warfarin); IP	Hospital LOS, readmission, cost findings	IP: rivaroxaban, warfarin; OP: not reported (IP-only study)	Rivaroxaban use was associated with a 1.36-day shorter LOS and $2,304 reduction in total costs compared to parenterally bridged warfarin. No difference in VTE recurrence or major bleeding	6, 8, 9, 14, 18	Discharge location not reported; In a subanalysis limited to low-risk patients, rivaroxaban was associated with a $1,855 reduction
Dasta et al (2015)^Citation45
Retrospective claims analysis/Premier Perspective Comparative Hospital Database/January 1, 2009–March 1, 2013	DVT or PE, n=64,503; PE, n=35,550; DVT, n=28,953; IP	Hospital LOS, resource utilization, cost findings	IP: warfarin, UH, LMWH, unspecified anticoagulant; OP: not reported (IP-only study)	Mean LOS was 4.7 (DVT) and 5.4 (PE) days, 9.9% (DVT) and 24.2% (PE) had ICU stay. For both cohorts, the first 3 days of hospitalization were costliest; costs stabilized on third day	6, 9, 10	Discharge location not reported
Deitelzweig et al (2016)^Citation53
Retrospective propensity-score matched cohort/Truven Health Analytic MarketScan Claims database/January 2011–December 2013 (conf abstract)	DVT; n=512 in each group: rivaroxaban vs LMWH/warfarin; OP	Cost findings	IP: not reported; OP: rivaroxaban, LMWH, warfarin (OP only study)	Mean all-cause total costs lower for rivaroxaban vs LMWH/warfarin over first 4 weeks (significant in weeks 1 and 2). Pharmacy costs significantly lower for rivaroxaban for each of the first 4 weeks	3, 4, 5, 6, 9, 14, 17, 22, 23, 24	OP study Discharge location not reported
Dubois et al (2015)^Citation48
Retrospective chart review/Florida Hospital Orlando/January 1, 2012–November 1, 2013 (conf abstract)	PE, n=59; rivaroxaban, n=10; SOC unmatched, n=47; SOC matched, n=10; IP	Hospital LOS, complications, cost findings	IP: rivaroxaban, IV UH, LMWH, fondaparinux; OP: not reported (IP-only study)	Rivaroxaban and SOC produced similar LOS, cost, and minor bleeds (there were no major bleeds)	1, 4, 5, 6, 8, 9, 14, 17, 18, 19, 23, 24	Discharge location not reported; in matched analysis, there were only 10 in each group
Fanikos et al (2013)^Citation43
Retrospective, hospital chart and database/Brigham and Women’s Hospital, Boston/September 2003–May 2010	PE, n=991; IP	Hospital LOS, readmission, resource utilization, complications, mortality, cost findings	IP: LMWH, UH, fondaparinux, bivalirudin, argatroban, lepirudin, warfarin; OP: not reported (IP-only study)	Mean total hospital cost per patient $8,764. Pharmacy costs ($966) were dominated by the use of LMWH ($232)	9, 14, 17	Discharge location not reported
Kahler et al (2015)^Citation35
Case–control/hospital administrative database and medical charts/January–December 2013	VTE, n=97; rivaroxaban, n=50; LMWH/warfarin, n=47; IP and OP	Mortality, cost findings	IP: rivaroxaban, LMWH, warfarin; OP: same	Over 6 months, cases treated with rivaroxaban had median total charges of $4,787 compared to $11,128 for controls treated with LMWH-warfarin; Of 47 control patients, 38.0% (all DVT) were treated at home	6, 14	Subgroup analysis of DVT and PE subgroups demonstrated lower charges and costs for rivaroxaban Discharge location not reported
Kahler and Kline (2014)^Citation36
Case–control/hospital data/6 months starting April 2013 (conf abstract)	VTE, n=32 (16 cases, 16 controls); IP and OP	Complications, mortality, cost findings	IP: rivaroxaban, other (not specified); OP: rivaroxaban	Median cost of care for cases (rivaroxaban) was $6,628 vs $12,021 for controls	3, 4, 5, 6, 7, 9, 11b, 14, 17, 21, 23, 24	Discharge location not reported
LaMori et al (2015)^Citation33
Retrospective claims analysis/NIS database/2011	DVT and PE, n=330,044; DVT, n=143,417; PE, n=186,627; IP	Hospital LOS, readmission, mortality, cost findings	IP and OP: not reported	In 2011, fewer DVT hospitalization and lower initial hospitalization cost than for PE. Readmissions occurred in 4.2% of DVT and 4.0% of PE, with 75.0%–80.0% within same or following month as initial event. Among DVT, 54.0% discharged home, 17.0% home health, 12.0% skilled nursing	6, 8, 9, 14, 17	DVT patients: 53.8% had a routine discharge (to the patients home), 16.7% received home health care, 12.3% were discharged to a skilled nursing facility; PE patients, 54.9% had a routine discharge to home, 14.5% received home health care, and 9.2% were discharged to a skilled nursing facility
Lin et al (2014)^Citation41
Retrospective	VTE, n=43,784; recurrent, n=6,153; no recurrence, n=37,631; IP and OP	Hospital LOS, readmission, resource utilization, cost findings	IP: not reported; OP: UH, LMWH, warfarin, fondaparinux	Recurrent VTE occurred in 15.4% of commercially insured and 11.4% of Medicare insured patients within 12 months, despite anticoagulation therapy. Recurrent VTE associated with substantial resource utilization and costs	9, 14	Discharge location not reported
Margolis et al (2016)^Citation32
Retrospective matched cohort/Truven Health MarketScan Hospital Drug Database/November 1, 2012–December 31, 2013	DVT or PE, n=2,446; PE, n=751; DVT, n=472; IP	Hospital LOS, time to discharge, resource utilization, mortality, cost findings	IP: rivaroxaban, warfarin; OP: not reported	Rivaroxaban had shorter LOS than warfarin (3.7 vs 5.2 days), shorter time to discharge (2.4 vs 3.9 days), and lower unadjusted mean total hospital costs ($8,688 vs $9,823); overall mean pharmacy costs not significantly different, but IP pharmacy costs were higher for rivaroxaban patients; in both cohorts, 86.0% discharged home and 13.0% transferred	6, 9	86.0% discharged home, 13.0% transferred to another facility, 1.0% other
Margolis et al (2016)^Citation34
Retrospective matched cohort/Truven Health MarketScan Hospital Drug Database/November 1, 2012–December 31, 2013	PE, n=751 in each group: rivaroxaban vs warfarin; IP and OP	Hospital LOS, time to discharge, resource utilization, cost findings	IP: rivaroxaban, warfarin; OP: not reported	Rivaroxaban associated with shorter LOS (3.8 days) vs warfarin (5.4, P<0.001), as was time to discharge and total mean hospital costs ($8,473 vs $10,291 P<0.001)	6, 9	Most patients discharged to home or home health; 11.0%–13.0% transferred
Merli et al (2016)^Citation47
Retrospective matched cohort/Truven Health MarketScan Hospital Drug Database/January 2011–December 2013	DVT, n=6,481 (unmatched cohort); n=670 (matched cohort); IP	Cost findings	IP: rivaroxaban, LMWH, warfarin; OP: not reported (IP-only study)	Index hospitalization costs were $1,508 less for rivaroxaban vs LMWH/warfarin users; main driver of difference is lower proportion of rivaroxaban patients hospitalized (60.0% vs 82.0%)	8, 9	Discharge location not reported; total hospital costs were also lower for rivaroxaban patients within 1, 2, 3, and 6 months (significantly within 1 and 3 months)
Raphael et al (2014)^Citation40
Retrospective/hospital data/January 2000–December 2010	PE, n=294; IVCF with heparin, n=91; IVCF without heparin, n=118; heparin without IVCF, n=55; no heparin, no IVCF, n=30; IP	Hospital LOS, resource utilization, complications, mortality, cost findings	IP: warfarin, heparin; OP: not reported (IP-only study)	Among warfarin patients, IVCF use was associated with fewer complications and lower overall costs	2, 6, 9, 14, 23	Discharge location not reported
Shorr et al (2014)^Citation37
Retrospective claims analysis/claims data/January 1, 2007–March 31, 2013 (conf abstract)	VTE, n=123,665 IP and OP	Hospital LOS, readmission, cost findings	IP: warfarin, enoxaparin, rivaroxaban, IVCF; OP: warfarin, enoxaparin, rivaroxaban	27.0% of patients were hospitalized at least once (any cause) within 1 year of VTE; 37.0% of those patients had at least one hospitalization for VTE. Subsequent hospitalization carried significant costs	3, 4, 6, 7, 9, 14, 17, 18, 22, 23, 24	Discharge location not reported
Weeda et al (2016)^Citation46
Retrospective/Hartford Hospital, CT/November 1, 2012–May 12, 2015	PE, n=190; IP	Hospital LOS, resource utilization, mortality, cost findings	IP: rivaroxaban, UH, LMWH, warfarin; OP: not reported (IP-only study)	Rivaroxaban was associated with lower adjusted hospital costs (range: –$3,835 to –$7,094) than heparin bridging to warfarin. Rivaroxaban patients also had a shorter adjusted LOS	6, 9, 14	Discharge location not reported
Weeda et al (2017)^Citation39
Retrospective claims analysis/Premier Perspective Comparative Hospital Database/November 2012–September 2015	PE, n=8,824 (4,412 in each 1:1 matched cohort); IP	Hospital LOS, readmission, resource utilization, complications, mortality, cost findings	IP: rivaroxaban, UH, LMWH, fondaparinux, warfarin; OP: not reported (IP-only study)	Rivaroxaban was associated with shorter LOS (1.4 days) and lower costs (–$2,322) vs parenterally bridged warfarin. No difference in readmission for VTE or major bleeding	6, 9, 14	Discharge location not reported; Subanalysis on low-risk patients produced similar results

Abbreviations: AF, atrial fibrillation; CHEERS, Consolidated Health Economic Evaluation Reporting Standards; conf, conference; DOAC, direct oral anticoagulant; DVT, deep vein thrombosis; ICU, intensive care unit; IP, inpatient; IV, intravenous; IVCF, inferior vena cava filter; LMWH, low-molecular-weight heparin; LOS, length of stay; NIS, National Inpatient Sample; OP, outpatient; PE, pulmonary embolism; SOC, standard of care; UH, unfractionated heparin; VKA, vitamin K antagonist; VTE, venous thromboembolism.

Table S1 MEDLINE clinical search strategy – conducted December 1, 2016

Step	Search terms	Abstracts
1	Search ((“Venous Thromboembolism”[Majr]) OR “Pulmonary Embolism”[Majr]) OR “Venous Thrombosis”[Majr]	63,522
2	Search (venous thromboemboli*[Title] OR vte[Title] OR venous thrombosis[Title] OR venous thromboses[Title] OR pulmonary thromboembolism*[Title] OR pulmonary embolism*[Title] OR deep venous thrombosis[Title] OR deep vein thrombosis[Title] OR deep vein thromboses[Title] OR deep venous thromboses[Title] OR dvt[Title]) Note: Steps 1 and 2 are keyword terms and Mesh indexing terms that are specific to the indications of interest.	36,211
3	Search #1 OR #2	69,728
4	Search clinical outcome*[Title/Abstract] OR Tx outcome*[Title/Abstract] OR discharge*[Title/Abstract] OR practice pattern*[Title/Abstract] OR Tx pattern*[Title/Abstract] OR patient management[Title/Abstract] OR long-term management[Title/Abstract] OR long-term Tx*[Title/Abstract] OR extended Tx[Title/Abstract] OR long-term care[Title/Abstract] OR extended care[Title/Abstract] OR outpatient*[Title/Abstract] OR IP*[Title/Abstract] OR home health care[Title/Abstract] OR home self-care[Title/Abstract] OR switch*[Title/Abstract] OR transition*[Title/Abstract] OR nursing home*[Title/Abstract] OR rehabilitation[Title/Abstract]	1,121,187
5	Search (((((“Tx Outcome”[Mesh]) OR “Practice Patterns, Physicians’”[Mesh]) OR “Patient Discharge”[Mesh]) OR “Long-Term Care”[Mesh]) OR “IPs”[Mesh]) OR “Ambulatory Care”[Mesh] Note: Steps 4 and 5 outline key terminology and Mesh terms that are specific to the concept of Tx patterns for IP and discharged patients.	914,978
6	Search #4 OR #5	1,871,693
7	Search #3 AND #6	10,207
8	Search dabigatran[Title/Abstract] OR rivaroxaban[Title/Abstract] OR apixaban[Title/Abstract] OR edoxaban[Title/Abstract] OR NOAC[Title/Abstract] OR anticoagulant*[Title/Abstract] OR VKA[Title/Abstract] OR vitamin K antagonist*[Title/Abstract] OR warfarin[Title/Abstract]	66,882
9	Search “Anticoagulants/therapeutic use”[Mesh] Note: Steps 8 and 9 are used to focus results to the drugs of interest.	50,512
10	Search #8 OR #9	94,383
11	Search #7 AND #10	4,010
12	Search prophylactic[Title] OR prophylaxis[Title] OR prevent*[Title] OR thromboprophyla*[Title] Note: Step 12 is included to eliminate articles that are primarily focused on prophylactic Tx.	289,300
13	Search #11 NOT #12	3,050
14	Search #13 NOT: Comment; Editorial; Letter; Meta-Analysis; Review	2,179
15	Search #14 Filters: Publication date from 2011/01/01 to 2016/12/31; English	790

Table S2 MEDLINE economic search strategy – conducted December 1, 2016

Step	Search terms	Abstracts
1	Search ((“Venous Thromboembolism”[Majr]) OR “Pulmonary Embolism”[Majr]) OR “Venous Thrombosis”[Majr]	63,522
2	Search (venous thromboemboli*[Title] OR vte[Title] OR venous thrombosis[Title] OR venous thromboses[Title] OR pulmonary thromboembolism*[Title] OR pulmonary embolism*[Title] OR deep venous thrombosis[Title] OR deep vein thrombosis[Title] OR deep vein thromboses[Title] OR deep venous thromboses[Title] OR dvt[Title]) Note: Steps 1 and 2 are keyword terms and Mesh indexing terms that are specific to the indications of interest.	36,211
3	Search #1 OR #2	69,728
4	Search dabigatran[Title/Abstract] OR rivaroxaban[Title/Abstract] OR apixaban[Title/Abstract] OR edoxaban[Title/Abstract] OR NOAC[Title/Abstract] OR anticoagulant*[Title/Abstract] OR VKA[Title/Abstract] OR vitamin K antagonist*[Title/Abstract] OR warfarin[Title/Abstract]	66,882
5	Search “Anticoagulants/therapeutic use”[Mesh]	50,512
6	Search #4 OR #5	94,383
7	Search #3 AND #6	13,720
8	Search economic*[Title/Abstract] OR cost[Title/Abstract] OR costly[Title/Abstract] OR costs[Title/Abstract] OR price*[Title/Abstract] OR reimburs*[Title/Abstract] OR health resource utili*[Title/Abstract] OR resource utili*[Title/Abstract] OR resource use*[Title/Abstract] OR claim*[Title/Abstract]	680,024
9	Search “Economics”[Mesh]) OR “Health Care Costs”[Mesh] OR “Drug Utilization”[Mesh] OR “Health Resources/utilization”[Mesh] Note: Specific keywords and Mesh terminology in Steps 8 and 9 are incorporated to focus the results to economic areas of interest.	550,224
10	Search #8 OR #9	1,045,295
11	Search #7 AND #10	925
12	Search prophylactic[Title] OR prophylaxis[Title] OR prevent*[Title] OR thromboprophyla*[Title]	289,300
13	Search #11 NOT #12	558
14	Search #13 NOT: Comment; Editorial; Letter; Meta-Analysis; Review	339
15	Search #14 Filters: Publication date from 2011/01/01 to 2016/12/31; English	116

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