Is there any efficacy difference between apixaban and rivaroxaban in morbidly obese patients (BMI

Is there any efficacy difference between apixaban and rivaroxaban in morbidly obese patients (BMI > 40)?

Comment by InpharmD Researcher

Available evidence evaluating apixaban and rivaroxaban in morbidly obese patients (BMI ≥40–50 kg/m² or weight >120 kg) is derived primarily from observational studies. In these studies, both agents demonstrated comparable efficacy in preventing venous thromboembolism (VTE) recurrence and thromboembolic events, with no indication of reduced effectiveness at higher body weights. However, some data suggest that bleeding rates may be slightly higher with rivaroxaban than with apixaban, although these differences were not statistically significant. Furthermore, pharmacokinetic analyses show that standard doses of both agents achieve therapeutic concentrations similar to those observed in non-obese patients.

Background

The use of DOACs in patients who are morbidly obese (>120 kg or BMI> 40 kg/m^2) is controversial, as evidence is scarce. A 2016 guidance statement from the International Society on Thrombosis and Hemostasis (ISTH), along with an updated communication published in 2021, does not recommend using direct oral anticoagulants (DOACs) in patients with a body mass index (BMI) of >40 kg m^2 or a weight of >120 kg due to limited clinical data. The available pharmacokinetic/pharmacodynamic evidence suggests decreased drug exposures, reduced peak concentrations, and shorter half-lives with increasing weight, which raises concerns about underdosing in the population with extreme weight. If a DOAC was to be used in morbidly obese patients, then they suggest checking a drug-specific peak and trough level (anti-FXa for apixaban, edoxaban, and rivaroxaban; ecarin time or dilute thrombin time with appropriate calibrators for dabigatran; or mass spectrometry drug level for any of the DOACs). If the level falls within the expected range, the continuation of the DOAC seems reasonable. The guidance makes no preference among DOACs. [1], [2]

A 2024 review article summarized evidence on the pharmacokinetic and clinical performance of DOACs in patients at extremes of body weight, noting that such populations remain underrepresented in randomized trials. The review aimed to evaluate available data on the pharmacokinetic and pharmacodynamic profiles of DOACs for venous thromboembolism (VTE) treatment and stroke prevention in nonvalvular atrial fibrillation (NVAF). Although evidence was limited, apixaban and rivaroxaban demonstrated favorable profiles in obese patients, showing efficacy and safety comparable to standard therapy. Very few data were available for dabigatran and edoxaban, with the latter appearing safer at lower doses in underweight patients. These findings were consistent with current guidance recommending apixaban and rivaroxaban for morbidly obese patients (BMI ≥40 kg/m² or >120 kg). Across studies reviewed, rivaroxaban maintained similar rates of recurrent VTE and major bleeding compared with standard therapy in patients with BMI ≥35 kg/m², including those exceeding 140 kg. Observational data confirmed that rivaroxaban plasma concentrations remained consistent across body weight categories, and no dose adjustment appeared necessary. Similarly, apixaban demonstrated stable pharmacokinetics in obese populations, with anti-Xa activity showing no correlation with BMI. In patients with BMI >40 kg/m² or weight >120 kg, both drugs maintained on-therapy anticoagulant levels and comparable efficacy and safety outcomes, supporting the use of standard doses in morbidly obese patients. [3]

A 2020 meta-analysis included a combination of five retrospective studies and randomized controlled trials (RCTs) that compared the use of DOACs to warfarin in morbidly obese patients for VTE recurrence. The results of this analysis found DOACs to be non-inferior to warfarin in reducing VTE recurrence in these patients (odds ratio [OR] 1.07; 95% confidence interval [CI] 0.93 to 1.23) and major bleeding events (OR 0.80; 95% CI 0.54 to 1.17). The authors concluded that the use of DOACs may be safe and effective in patients >120 kg or BMI >40 kg/m^2. None of the included trials or subanalyses compared rivaroxaban to apixaban head-to-head. [4]

Published evidence on the use of DOACs in patients at extremes of body weight found no significant differences in DOAC safety or effectiveness between patients with a BMI of <30 kg/m^2 and those with a BMI of ≥30 kg/m^2. Between dabigatran, rivaroxaban, apixaban, or vitamin K antagonist (VKA) therapy, results were similar; however, there was a higher incidence of transient ischemic attack (TIA) with dabigatran compared to rivaroxaban and apixaban. Authors recommend avoiding dabigatran in obese patients due to an unfavorable pharmacokinetic profile and lack of strong efficacy data. In the context of VTE and nonvalvular atrial fibrillation (NVAF), safety and efficacy data suggest rivaroxaban is comparable to warfarin, while apixaban has a more favorable safety profile. However, the authors note that available data are largely retrospective and of low quality. [5], [6], [7]

A 2020 systematic review and meta-analysis compared the safety and efficacy of DOACs versus VKA and low-molecular-weight heparin (LMWH) therapy for the treatment of VTE in patients with obesity and morbid obesity (BMI >40 kg/m^2). The incidence of VTE recurrence in patients with a BMI >30 kg/m^2 was similar between DOACs and VKA/LMWH therapy (835% vs. 8.2%; risk ratio [RR] 1.03; 95% CI 0.93 to 1.15). A similar result was seen in morbidly obese patients (15.7% vs. 14.9%; RR 1.06; 95% CI 0.94 to 1.19). Both analyses had acceptable heterogeneity (I^2= 0% for both), but they were heavily weighted (>79%) by one study comparing rivaroxaban to warfarin. DOACs were significantly associated with fewer major bleeding events in both obese (RR 0.57; 95% CI 0.34 to 0.94; p= 0.03) and morbidly obese (RR 0.71; 95% CI 0.50 to 1.00; p= 0.05) subgroups than those of VKA/LMWH subgroups. Neither safety nor efficacy was examined among DOACs. This analysis primarily used observational data, including unpublished poster presentations. [8]

Literature Review

A search of the published medical literature revealed 10 studies investigating the researchable question:

Is there any efficacy difference between apixaban and rivaroxaban in morbidly obese patients (BMI > 40)?

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-10 for your response.

Apixaban and rivaroxaban in obese patients treated for venous thromboembolism: drug levels and clinical outcomes
Design	Prospective observational study in two French University hospitals N= 146
Objective	To assess rivaroxaban and apixaban concentrations at different time-points after intake, in obese patients followed at a thrombosis center and treated for VTE; to define factors associated with DOAC levels outside the on-therapy ranges; and to evaluate bleeding and thrombosis rates during follow-up
Study Groups	Apixaban 5mg twice daily (n= 47) Apixaban 2.5 mg twice daily (n= 22) Rivaroxaban 20mg once daily (n= 74) Rivaroxaban 10 mg once daily (n= 1) Rivaroxaban 15 mg twice daily (n= 2)
Inclusion Criteria	Consecutive adult obese patients (BMI≥30 kg/m2) receiving apixaban or rivaroxaban for VTE treatment and followed in the outpatient thrombosis clinics of Rennes and Brest University Hospitals between August 2017 and January 2019
Exclusion Criteria	No specific exclusion criteria mentioned
Methods	Apixaban or rivaroxaban plasma concentrations were measured after the first visit, regardless of last intake. Concentrations were compared to published reference values for non-obese patients. Demographic, clinical, biological and therapeutic data were collected. Univariate and multivariate analyses were performed to identify factors associated with DOAC concentrations outside the on-therapy ranges
Duration	August 2017 to January 2019
Outcome Measures	DOAC concentrations at different time-points
Baseline Characteristics		All patients (n=146)
	Gender (women)	70 (48%)
	Age (years)	61 (19-86)
	Weight (kg)	100 (73-178)
	BMI (kg/m2)	34.5 (30-54)
	BMI 30-34.9 kg/m2	79 (54%)
	BMI 35-39.9 kg/m2	38 (26%)
	BMI >40	29 (20%)
	Creatinine (µmol/L)	77 (44-155)
	Creatinine clearance (mL/min)	125 (40-328)
Results		All patients (n=146)
	Apixaban 5 mg twice daily n=47 Delay since last intake (hours) Concentration (ng/mL)	5.5 (1.5-12) 103 (23-300)
	Apixaban 2.5 mg twice daily n=22 Delay since last intake (hours) Concentration (ng/mL)	3 (1-6) 58 (20-114)
	Rivaroxaban 20 mg once daily n=77 Delay since last intake (hours) Concentration (ng/mL)	7 (1-28) 108 (20-453)
	Among 146 included obese patients (47% apixaban 2.5 to 5 mg BID; 51% rivaroxaban 20 mg once daily), one hundred twenty-four (124; 85%) had DOAC concentrations similar to those of nonobese patients, whereas 22 (15%), mainly in the rivaroxaban group (17/22; 77.3%), had DOAC concentrations outside the on-therapy ranges (5th-95th percentiles of observed concentrations). Age ≤63 years old, use of rivaroxaban, and time since last intake ≤8h were significantly associated with DOAC concentrations outside the on-therapy ranges.
Adverse Events	2 (1%) patients had recurrent VTE, none had major bleeding and 11 (8%) had minor bleeding
Study Author Conclusions	In this specific prospective bi-centric study dedicated to VTE obese patients, use of DOACs at fixed doses led to concentrations similar to those of non-obese patients in a high proportion of patients, without any effect of the BMI, and with risk-benefit profile comparable to non-obese patients.
Critique	The study's strengths include its prospective design, accurate timing of DOAC intake and sampling, and a large sample size. However, it was not designed to assess clinical outcomes, and DOAC concentrations were not measured at the time of recurrent or hemorrhagic events, limiting the ability to establish a direct relationship between concentrations and clinical outcomes.

References:

Ballerie A, Nguyen Van R, Lacut K, et al. Apixaban and rivaroxaban in obese patients treated for venous thromboembolism: Drug levels and clinical outcomes. Thromb Res. 2021;208:39-44. doi:10.1016/j.thromres.2021.10.009

Safety and efficacy of apixaban and rivaroxaban in obese patients with acute venous thrombosis/embolism
Design	Retrospective, observational, single-center study N= 499
Objective	To retrospectively analyze the use and 60-day outcomes of two direct-acting oral anticoagulants (DOACs), apixaban and rivaroxaban, prescribed to severely obese patients after venous thromboembolism (VTE)
Study Groups	Apixaban (n= 203) Rivaroxaban (n= 296)
Inclusion Criteria	Severely obese patients (BMI ≥40 kg/m²); aged ≥18 years; diagnosed with acute VTE; treated with either rivaroxaban or apixaban
Exclusion Criteria	Chronic VTE diagnosis; received anticoagulation other than DOACs
Methods	This was a retrospective chart review of severely obese patients treated for VTE with apixaban or rivaroxaban at a single health system in Michigan. Data abstracted from electronic medical records included age, sex, race, BMI, and post-admission diagnoses of VTE or bleeding.
Duration	January 2013 to January 2020
Outcome Measures	Primary: development of new VTE or progression of prior VTE within 60 days of DOAC initiation Secondary: bleeding events, length of stay, mortality within 60 days
Baseline Characteristics		Apixaban (n= 203)	Rivaroxaban (n= 296)	p-value
	Age, years	58.8 ± 14.0	56.5 ± 13.9	0.069
	Female	73.4%	64.2%	0.003
	BMI, kg/m² (range)	44.6 (39.5-88.4)	44.3 (40.0-86.4)	0.617
	Race Caucasian Black Other	63% 35% 2%	81.6% 17.7% 0.7%	-
Results		Apixaban (n= 203)	Rivaroxaban (n= 296)	p-value
	VTE recurrence	1 (0.5%)	2 (0.7%)	1.000
	Mortality	13 (6.4%)	21 (7.1%)	0.764
	Length of stay, days (range)	5 (0-66)	3.5 (0-38)	0.003
	Bleeding Vaginal/uterine Gastrointestinal Hematuria Hematoma Epistaxis	12 (5.9%) 5/12 (41.7%) 3/12 (25%) 0 3/12 (25%) 1/12 (8.3%)	23 (7.8%) 6/23 (26.1%) 7/23 (30.4%) 6/23 (26.1%) 2/23 (8.7%) 2/23 (8.7%)	0.427
Adverse Events	There were two clotting events in the rivaroxaban arm (0.7%) compared to one in the apixaban arm (0.5%), which was not a statistically significant difference (p= 1.000).
Study Author Conclusions	This study indicates that apixaban and rivaroxaban are not associated with an increase in VTE recurrence. Bleeding rates were slightly higher in the rivaroxaban group compared to the apixaban group in severely obese patients, though not significantly different.
InpharmD Researcher Critique	This study is limited by its retrospective, single-center design which is susceptible to confounding. This study only included patients who presented to the hospital and at a 60-day follow-up with physicians in the same health system, which may present a selection bias in this population. The short follow-up period of 60 days presents a possibility of recurrent VTE beyond that time frame. Dosing of the DOACs (i.e., standard dose vs. adjusted dose) was not discussed in this study.

References:

Anusim N, Ghimire B, Smalley M, Jaiyesimi I, Gaikazian S. Safety and efficacy of apixaban and rivaroxaban in obese patients with acute venous thrombosis/embolism. Eur J Haematol. 2022;109(4):409-412. doi:10.1111/ejh.13817

Efficacy and safety of direct oral factor Xa inhibitors compared with warfarin in patients with morbid obesity: a single-centre, retrospective analysis of chart data
Design	Single-center, retrospective chart review N=795
Objective	To investigate the efficacy and safety of the direct oral anticoagulants apixaban and rivaroxaban in comparison with warfarin in morbidly obese patients
Study Groups	Apixaban (n=150) Rivaroxaban (n=326) Warfarin (n=319)
Inclusion Criteria	Aged ≥18 years; BMI ≥40 kg/m²; started on oral anticoagulation with apixaban, rivaroxaban, or warfarin for atrial fibrillation or venous thromboembolism; had at least one follow-up visit after anticoagulation initiation
Exclusion Criteria	Had both atrial fibrillation and venous thromboembolism, had no follow-up after being prescribed the DOAC
Methods	This was a retrospective analysis of chart data from a single center in New York. Outcomes of recurrent venous thromboembolism, stroke, and bleeding were measured from the first prescription date to the earliest of a thrombotic event, medication discontinuation, death, or end of the study on June 30, 2017. Patients were stratified based on anticoagulation indication: atrial fibrillation (Afib) or venous thromboembolism (VTE).
Duration	March 2013 to March 2017 Median follow-up: 359.4 days (Afib); 196 (VTE)
Outcome Measures	Primary: recurrent VTE in VTE patients; stroke in AFib patients; major bleeding
Baseline Characteristics		Apixaban (n=150)	Rivaroxaban (n=326)	Warfarin (n=319)
	Age, years VTE (n=366) AFib (n=429)	53.3 ± 13.9 65.9 ± 10.7	52.4 ± 14.7 60.9 ± 12.6	52.6 ± 14.5 66.8 ± 13.6
	Female	93 (62%)	195 (59.8%)	208 (65.2%)
	BMI, kg/m²(IQR) VTE (n=366) AFib (n=429)	43.3 (41.2-49.4) 43.8 (41.0-48.1)	43.7 (41.1-48.8) 44.6 (41.8-48.6)	45.3 (41.3-50.1) 44.5 (41.7-52.3)
	BMI ≥50 kg/m²	29 (19.3%)	67 (20.6%)	96 (30.1%)
	Follow-up, days (IQR) VTE (n=366) AFib (n=429)	163.3 (90.0–233.3) 331.5 (181.5–577.0)	217.4 (94.4–514.1) 412.9 (187.3–675.2)	206.3 (64.4–540.3) 293.6 (81.6–671.8)
Results		Apixaban (n=150)	Rivaroxaban (n=326)	Warfarin (n=319)
	Recurrent VTE VTE group (n=366)	1/47 (2.1%)	3/152 (2.0%)	2/167 (1.2%)
	Stroke AFib (n=429)	1/103 (1.0%)	4/174 (2.3%)	2/152 (1.3%)
	Major bleeding VTE (n=366) AFib (n=429)	4 (2.7%) 1/47 (2.1%) 3/103 (2.9%)	7 (2.1%) 2/152 (1.3%) 5/174 (2.9%)	16 (5.0%) 4/167 (2.4%) 12/152 (7.9%)
Adverse Events	Composite bleeding VTE: apixaban 4%; rivaroxaban 9%; warfarin 10% AFib: apixaban 11%; rivaroxaban 10%; warfarin 16%
Study Author Conclusions	This study provides further evidence of similar efficacy and safety between the direct oral anticoagulants apixaban and rivaroxaban, and warfarin in morbidly obese patients with atrial fibrillation and venous thromboembolism.
InpharmD Researcher Critique	Limitations of this study include the retrospective and single-center design. The low number of events also limited the ability of this study to conduct additional statistical analyses. This study (the Bronx, NY) also had a high proportion of Black and Hispanic patients. Although patients could have had unrecorded events if they were treated at another clinic, this center covers most of the study population so it was likely any events were documented within the system.

References:

Kushnir M, Choi Y, Eisenberg R, et al. Efficacy and safety of direct oral factor Xa inhibitors compared with warfarin in patients with morbid obesity: a single-center, retrospective analysis of chart data. Lancet Haematol. 2019;6(7):e359-e365. doi:10.1016/S2352-3026(19)30086-9

A Real-World Comparison of Apixaban and Rivaroxaban in Obese and Morbidly Obese Patients With Nonvalvular Atrial Fibrillation
Design	Retrospective cohort study N= 303
Objective	To evaluate the comparative effectiveness and safety of apixaban and rivaroxaban in both obese and morbidly obese patients with NVAF
Study Groups	Apixaban (n= 212) Rivaroxaban (n= 121)
Inclusion Criteria	Patients 18 years or older, diagnosed with NVAF, prescribed apixaban or rivaroxaban for ≥3 months, and having a BMI ≥ 30 kg/m2
Exclusion Criteria	Received DOACs for indications other than preventing stroke or embolism in NVAF
Methods	Retrospective chart review conducted at a single outpatient cardiovascular clinic. Patients started on either DOAC from October 2014 to January 2021 were evaluated. Baseline characteristics were determined from the index outpatient visit where DOAC use was first identified. The primary endpoint was the composite rate of stroke, TIA, MI, or presence of atrial thrombosis. Bleeding events were evaluated as the primary safety endpoint
Duration	October 2014 to January 2021
Outcome Measures	Primary: Composite rate of stroke, TIA, MI, or presence of atrial thrombosis Secondary: Components of the primary endpoint evaluated individually, clinically relevant non-major and major bleeding events, all-cause mortality
Baseline Characteristics		Rivaroxaban (n = 121)	Apixaban (n = 212)
	Age, years (mean ± SD)	69.5 ± 10.4	71.4 ± 10.0
	Age ≥65 (n, %)	86 (71.1%)	159 (75.0%)
	Male (n, %)	66 (54.5%)	124 (58.5%)
	Drinks alcohol (n, %)	12 (9.9%)	42 (19.8%)
	BMI, kg/m2 (mean ± SD)	38.3 ± 7.5	37.2 ± 6.9
	Morbidly obese (n, %)	32 (26.4%)	61 (28.8%)
	HAS-BLED score (mean ± SD)	1.7 ± 1.0	2.03 ± 1.1
	Renal disease (n, %)	26 (21.5%)	26 (12.3%)
	History of bleeding (n, %)	5 (4.1%)	24 (11.3%)
Results		Rivaroxaban (n = 121)	Apixaban (n = 212)	p-Value
	Primary composite (n, %) Atrial thrombosis MI Stroke TIA	2 (1.7%) 0 (0%) 0 (0%) 0 (0%) 2 (1.7%)	8 (3.8%) 1 (.5%) 1 (.5%) 1 (.5%) 5 (2.4%)	0.28
	Any bleeding event Clinically relevant, non-major bleeding Major bleeding	2 (1.7%) 2 (1.7%) 0 (0%)	6 (2.8%) 4 (1.9%) 2 (0.9%)	0.50
	Died (n, %)	0 (0%)	8 (3.8%)	0.03
Adverse Events	Bleeding events occurred more often in the apixaban arm, but this difference was not statistically significant. Overall mortality was higher in those prescribed apixaban (3.8% vs 0%, p= 0.03).
Study Author Conclusions	For obese and morbidly obese patients prescribed either apixaban or rivaroxaban for NVAF, rates of stroke, TIA, MI, and atrial thrombosis did not differ. The preferred DOAC for patients with class I-III obesity remains elusive, but current data points to a patient-centered approach for anticoagulant selection.
Critique	The study's retrospective nature and single-center design may limit generalizability. The small sample size and lack of power calculation could affect the reliability of the findings. Differences in baseline characteristics, such as alcohol use and prior bleeding events, may have skewed results. Despite these limitations, the study provides valuable insights into the comparative safety and efficacy of apixaban and rivaroxaban in obese patients with NVAF.

References:

Burnham KT, Yang T, Wooster J. A Real-World Comparison of Apixaban and Rivaroxaban in Obese and Morbidly Obese Patients With Nonvalvular Atrial Fibrillation. J Pharm Pract. Published online September 15, 2023. doi:10.1177/08971900231202643

Safety and efficacy of oral anticoagulants in extreme weights
Design	Retrospective review conducted at New York University Langone Hospital – Long Island N= 492
Objective	To evaluate the safety and efficacy of DOACs in underweight and obese patients compared to warfarin
Study Groups	Warfarin (n= 248) Apixaban (n= 101) R ivaroxaban (n= 100) Dabigatran (n= 43)
Inclusion Criteria	Inpatient hospital admission, patients receiving at least 90 days of apixaban, rivaroxaban, dabigatran, or warfarin as a home medication, BMI < 18.5 kg/m2 or BMI > 30 kg/m2, and history of either VTE or AF
Exclusion Criteria	DOAC or warfarin indication for hip or knee arthroplasty, anticoagulation therapy duration <90 days, a change in DOAC within 90 days from evaluation, and DOAC or warfarin initiation during the admission
Methods	Patients received a DOAC (apixaban, rivaroxaban or dabigatran) or warfarin for VTE or AF between October 2016 and September 2020. Data collected included age, gender, weight and BMI, creatinine clearance (CrCl), serum creatinine (SrCr), history of chronic kidney disease, history of cancer, history of previous VTE or AF, anticoagulant utilized, duration of anticoagulant use, suspected VTE, suspected stroke, bleed, or other, diagnostic used to diagnose VTE, stroke or bleed
Duration	October 2016 to September 2020
Outcome Measures	Primary: Occurrence of thrombosis or cerebral vascular accident, rates of bleeding Secondary: Rates of VTE, rates of ischemic stroke, rates of bleeding events in each BMI category
Baseline Characteristics		Warfarin (n= 248)	Apixaban (n= 101)	Rivaroxaban (n= 100)	Dabigatran (n= 43)	Overall DOAC (n = 244)
	Age (years)	72 (60, 82.5)	70 (63, 79)	70 (59.5, 80)	75 (69, 84)	71 (63, 79.5)
	Female	117 (47.18%)	52 (51.49%)	48 (48%)	24 (55.81%)	124 (50.82%)
	Weight (kg)	94 (74.2, 120.8)	95 (84, 108)	97 (82.5, 120)	95 (71, 115)	95.8 (83, 112.5)
	BMI <18.5 (kg/m2)	47 (18.95%)	10 (9.9%)	13 (13%)	10 (23.26%)	33 (13.52%)
	>30–35 (kg/m2)	104 (41.94%)	46 (45.54%)	43 (43%)	16 (37.21%)	105 (43.03%)
	>35–40 (kg/m2)	37 (14.92%)	28 (27.72%)	22 (22%)	9 (20.93%)	59 (24.18%)
	>40–45 (kg/m2)	25 (10.08%)	15 (14.85%)	17 (17%)	5 (11.63%)	37 (15.16%)
	>45–50 (kg/m2)	9 (3.63%)	1 (0.99%)	1 (1%)	2 (4.65%)	4 (1.64%)
	>50 (kg/m2)	26 (10.48%)	1 (0.99%)	4 (4%)	1 (2.33%)	6 (2.46%)
	History of cancer	19 (7.66%)	20 (19.8%)	26 (26%)	6 (13.95%)	52 (21.31%)
	History of AF	182 (73.39%)	76 (75.25%)	56 (56%)	39 (90.7%)	171 (70.08%)
	History of VTE	63 (25.4%)	32 (31.68%)	43 (43%)	11 (25.58%)	86 (35.25%)
	History of CKD/AKI	113 (45.56%)	51 (50.5%)	24 (24%)	19 (44.19%)	94 (38.52%)
	Indication for anticoagulation - VTE	65 (26.21%)	33 (32.67%)	42 (42%)	5 (11.63%)	80 (32.79%)
	Indication for anticoagulation - Atrial fibrillation/flutter	183 (73.79%)	68 (67.33%)	58 (58%)	38 (88.37%)	164 (67.21%)
Results	In patients with BMI > 40 kg/m², bleeding rates did not differ significantly between groups: 7 (12.5%) on DOACs versus 5 (8.33%) on warfarin (p = 0.2858), and across 4-groups (p = 0.3417). In BMI > 30–35 kg/m², bleeding risk was significantly higher with warfarin: 22 (20.95%) on DOACs versus 36 (34.62%) on warfarin (p = 0.0274). Among individual DOACs, bleeding occurred in apixaban 5 (10.87%), rivaroxaban 11 (25.58%), dabigatran 6 (37.5%), compared to warfarin 36 (34.62%) (p = 0.02). Warfarin was also associated with more hemoptysis/epistaxis—10 (9.62%) vs DOACs 2 (1.9%) (p = 0.0166). In BMI > 35–40 kg/m², bleeding rates were not statistically different: 11 (18.64%) on DOACs vs 13 (35.14%) on warfarin (p = 0.0694), and among 4-groups (apixaban 2 [7.14%], rivaroxaban 7 [31.82%], dabigatran 2 [22.22%], warfarin 13 [35.14%]; p = 0.0610). However, hematoma rates were significantly higher with warfarin 5 (13.51%) compared to apixaban 0 (0%), rivaroxaban 0 (0%), and dabigatran 1 (11.11%) (p = 0.048).
Adverse Events	Bleeding events were defined as either decrease in the hemoglobin level of ≥2 g/dL, or transfusion of ≥2 units PRBC, or occurring at a critical site, or resulting in death. In BMI <18.5, bleeding occurred in 11 (33%) patients on a DOAC compared to 7 (14.89%) patients on warfarin, p = 0.0519. Apixaban demonstrated statistically significant lower rates of bleeding, p = 0.0322. Dabigatran group had the highest bleeding events 5 (50%).
Study Author Conclusions	Patients with extreme body weights requiring anticoagulation for VTE and AF may safely benefit from DOAC therapy. Apixaban showed the lowest rate of VTE and bleeding compared to warfarin, rivaroxaban, and dabigatran, providing experience for clinicians to use DOACs, particularly apixaban, in underweight and obese populations.
Critique	The study provides valuable insights into the use of DOACs in extreme weights, highlighting the efficacy and safety of apixaban. However, the retrospective design and single-center nature may limit generalizability. The sample size for certain BMI categories was limited, and the study did not evaluate the impact of renal function on DOAC dosing, which could affect outcomes.

References:

Chin-Hon J, Davenport L, Huang J, Akerman M, Hindenburg A. Safety and efficacy of oral anticoagulants in extreme weights. Thromb Res. 2023;231:1-6. doi:10.1016/j.thromres.2023.09.001

Effectiveness and Safety of Direct Oral Anticoagulants versus Warfarin in Obese Patients with Acute Venous Thromboembolism
Design	Retrospective matched cohort study N=1,840
Objective	To evaluate the effectiveness and safety of direct oral anticoagulants (DOACs) versus warfarin for the treatment of acute venous thromboembolism (VTE) in obese patients
Study Groups	DOAC group (n= 632) Warfarin group (n= 1,208)
Inclusion Criteria	Age 18 years or older; a documented actual body weight >100kg and <300 kg in the electronic health record during the index visit; acute diagnosed with VTE; discharged with a DOAC (apixaban, dabigatran, or rivaroxaban) or warfarin
Exclusion Criteria	Atrial fibrillation, atrial flutter
Methods	This was a retrospective study from a health system consisting of 40 academic, community, and specialty hospitals in Pennsylvania. Data was collected via ICD-9 codes and clinical reports. Eligible patients were matched 2:1 using propensity scores based on a history of VTE, chronic kidney disease (CKD), race, and age.
Duration	January 2011 to October 2015 Follow-up: 12 months
Outcome Measures	Primary: Recurrence of VTE within 12 months of the index admission date Secondary: Occurrence of pulmonary embolism (PE) and deep vein thrombosis (DVT) even separately within the study time frame; bleeding that was similarly defined as any readmission with a primary admission ICD-9-CM or ICD-10-CM code for bleeding within 12 months of the index admission date
Baseline Characteristics		DOAC (n= 632)	Warfarin (n= 1,208)	p-Value
	Age, years (interquartile range)	55 (46-65)	55 (56-65)	0.64
	Female	216 (34.2%)	434 (35.9%)	0.46
	White	546 (86.4%)	1,055 (87.3%)	0.57
	Weight, kg (interquartile range) >120 >200 and <300	115 (106-132) 264 (41.8%) 7 (1.1%)	116 (107-132) 497 (41.1%) 25 (2.1%)	0.11 0.79 0.13
	Body mass index, kg/m²(interquartile range) 30-35 35-39 >40	38.8 (34.0-44.5) 98 (23.3%) 113 (26.9%) 183 (43.6%)	39.2 (34.4-45.3) 179 (23.7%) 197 (26.1%) 342 (45.3%)	0.44
	History of VTE	132 (20.9%)	237 (19.6%)	0.52
	History of cancer	45 (7.1%)	40 (3.3%)	<0.001
	Home anticoagulant	120 (19%)	152 (12.6%)	<0.001
	Of the DOAC group, rivaroxaban was the most used (91.8%), followed by apixaban (5.2%), and dabigatran (3%).
Results		DOAC (n= 632)	Warfarin (n= 1,208)	p-Value
	Recurrence of VTE within 12 months	41 (6.5%)	77 (6.4%)	0.93
	Occurrence of PE Occurrence of DVT	3.7% 3%	3.8% 3.5%	0.94 0.56
	Bleeding within 12 months Hospital readmission Emergency Department	11 (1.7%) 6 (0.9%) 5 (0.8%)	14 (1.2%) 11 (0.9%) 3 (0.2%)	0.31
	Gastrointestinal and genitourinary were the most common sources of bleeding for both groups.
Adverse Events	Bleeding events: gastrointestinal bleeding (1.1% vs 0.3%), genitourinary bleeding (0.3% vs 0.4%), hemoptysis (0.2% vs 0.2%)
Study Author Conclusions	To our knowledge, this is the largest clinical study to date showing that patients with obesity can be treated effectively and safely with a DOAC compared with warfarin for acute VTE. Thus, DOACs should be considered a reasonable alternative to warfarin for the treatment of acute VTE in obese patients.
InpharmD Researcher Critique	This study is limited by its retrospective design, which relies on complete and accurate documentation within the electronic health records. Clinical factors that could have influenced the use of a DOAC versus warfarin may not have been fully accounted for, including concomitant use of other medications, such as antiplatelet agents, that increase bleeding risk.

References:

Coons JC, Albert L, Bejjani A, Iasella CJ. Effectiveness and Safety of Direct Oral Anticoagulants versus Warfarin in Obese Patients with Acute Venous Thromboembolism [published correction appears in Pharmacotherapy. 2020 Jul;40(7):718]. Pharmacotherapy. 2020;40(3):204-210. doi:10.1002/phar.2369

Evaluation of the Efficacy of Direct Oral Anticoagulants (DOACs) in Comparison to Warfarin in Morbidly Obese Patients
Design	Retrospective cohort study N= 180
Objective	To evaluate the efficacy of the DOACs apixaban, rivaroxaban, and dabigatran in comparison to warfarin in preventing a composite of stroke and systemic emboli in morbidly obese patients
Study Groups	DOAC group (n= 90) Warfarin group (n= 90)
Inclusion Criteria	Adults 18 years or older; body mass index (BMI) >40 kg/m²; weight >120 kg
Exclusion Criteria	Patients on ritonavir, itraconazole, ketoconazole, clarithromycin, dronedarone, edoxaban, or betrixaban; CrCl <30 mL/min; recent diagnosis of atrial fibrillation or atrial flutter within 30 days with no evidence of transmural thrombi; history of head trauma; hepatic disease with coagulopathy
Methods	This was a retrospective study from a single-center in Texas assessing the use of DOACs in morbidly obese patients. Rates of ischemic stroke, pulmonary embolism (PE), deep vein thrombosis (DVT), myocardial infarction (MI), and major bleeding were analyzed in morbidly obese patients receiving apixaban, rivaroxaban, or dabigatran in comparison to warfarin for anticoagulation due to nonvalvular atrial fibrillation, postoperative thrombus prophylaxis, or DVT/PE treatment and/or reduction in risk for recurrence.
Duration	October 2012 to October 2017
Outcome Measures	Primary: composite of stroke, transient ischemic attack (TIA), DVT, or PE Secondary: frequency of each composite, major and non-major bleeding events (defined by Internation Society of Thrombosis and Hemostasis [ISTH] criteria for major bleeding), all-cause mortality
Baseline Characteristics		DOACs (n= 90)	Warfarin (n= 90)
	Age, years (IQR)	61 (24-89)	63 (18-89)
	Female	33 (36.7%)	42 (46.7%)
	White	100%	100%
	Therapy	46 (51.1%) apixaban 11 (12.2%) dabigatran 33 (36.7%) rivaroxaban	INR goal 2-3 (68% of the time within goal)
	Concomitant antiplatelet therapy	18 (20.0%)	21 (23.7%)
	Mean BMI, kg/m²	46.7	45.8
	Mean weight, kg	139.3	135.9
	Anticoagulation indication Atrial fibrillation DVT/PE treatment Postoperative prophylaxis	64 (71.1%) 23 (25.6%) 1 (3.3%)	56 (62.2%) 26 (28.9%) 8 (8.9%)
	IQR: interquartile range
Results		DOACs (n= 90)	Warfarin (n= 90)	Odds Ratio (95% CI)
	Composite stroke and systemic emboli Ischemic Stroke DVT PE MI	11 (12.2%) 3 (3.3%) 3 (3.3%) 1 (1.1%) 4 (4.4%)	10 (11.1%) 3 (3.3%) 2 (2.2%) 2 (2.2%) 3 (3.3%)	0.82 (-8.6 to 10.8) N/A 0.65 (-4.8 to 7.3) 0.56 (-4.1 to 6.7) 0.70 (-5.5 to 7.9)
	Death	0	0	N/A
	Major Bleeding	2 (2.2%)	3 (3.3%)	0.65 (-4.8 to 7.3)
		Events with the DOACs
		Apixaban (n= 46)	Rivaroxaban (n= 33)	Dabigatran (n= 11)
	Events Ischemic Stroke DVT PE MI Major bleeding	0 0 0 1 (2.4%) 1 (2.4%)	1 (3.0%) 2 (6.1%) 1 (3.0%) 2 (6.1%) 1 (3.0%)	2 (18.2%) 1 (9.1%) 0 1 (9.1%) 0
Adverse Events	N/A
Study Author Conclusions	This study found that rivaroxaban, apixaban, and dabigatran were not associated with an increase in stroke or systemic emboli in morbidly obese patients in comparison to warfarin. However, due to the small sample size and retrospective design, this conclusion can only be hypothesis-generating.
InpharmD Researcher Critique	Due to the study's retrospective design, causation cannot be implied between DOACs and stroke and systemic emboli risks. Additionally, retrospective datasets are poor choices for comparative analyses between therapies. There is also limited generalizability due to the small size and single-center design.

References:

Kalani C, Awudi E, Alexander T, Udeani G, Surani S. Evaluation of the efficacy of direct oral anticoagulants (DOACs) in comparison to warfarin in morbidly obese patients. Hosp Pract (1995). 2019;47(4):181-185. doi:10.1080/21548331.2019.1674586

Treatment of venous thromboembolism with rivaroxaban in relation to body weight: A sub-analysis of the EINSTEIN DVT/PE studies
Design	Post-hoc, sub-analysis of the EINSTEIN DVT/PE studies (open-label, randomized, multicenter, event-driven, non-inferiority studies) N=8230 (for the analysis per BMI)
Objective	To determine the incidence of major bleeding in patients with a low body weight and recurrent venous thromboembolism (VTE) in patients with a high body weight during rivaroxaban or enoxaparin/vitamin K antagonist (VKA) therapy
Study Groups	BMI <25 (n=2,481) BMI ≥25-30 (n =3,258) BMI ≥30-35 (n=1,630) BMI ≥35 (n=861)
Inclusion Criteria	Patients with acute symptomatic deep vein thrombosis (DVT) and/or pulmonary embolism (PE)
Exclusion Criteria	Another indication for a VKA, CrCl < 30 ml/min, liver disease, bacterial endocarditis, active bleeding or high risk of bleeding, systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mm Hg
Methods	Patients from the EINSTEIN DVT and EINSTEIN PE trials received either fixed-dose rivaroxaban 15 mg PO BID for 21 days, followed by 20 mg once daily or bodyweight-adjusted enoxaparin followed by a VKA (either warfarin or acenocoumarol; target INR: 2.0-3.0) for 3, 6, or 12 months of therapy. Follow-up assessed for signs and symptoms of bleeding or VTE recurrence.
Duration	359 days
Outcome Measures	Primary outcome: percentage of patients with symptomatic recurrent venous thromboembolism (EINSTEIN DVT/PE) Secondary outcomes: EINSTEIN DVT: percentage of patients with the composite variable comprising recurrent DVT, Non-fatal PE and all cause mortality EINSTEIN PE: major bleeding, death from any cause, vascular events (acute coronary syndrome, ischemic stroke, transient ischemic attack, systemic embolism)
Baseline Characteristics		BMI<25 (n=2,481)	BMI ≥ 25-30 (n=3,258)	BMI ≥ 30-35 (n=1,630)	BMI ≥ 35 (n=861)
	Median age, years (range)	56 (18-97)	60 (18-97)	60 (18-97)	55 (20-92)
	Men	1,221 (49.2%)	2,029 (62.3%)	894 (54.8%)	345 (40.1%)
	Index event DVT PE+DVT PE No confirmed event	43.9% 11.6% 43.3% 0.9%	40.0% 15.8% 43.4% 0.8%	40.1% 16.0% 42.8% 1.1%	37.0% 16.6% 45.4% 1.0%
	Unprovoked VTE	59.7%	63.8%	68.3%	63.9%
	Known thrombophilia	163 (6.6%)	195 (6.0%)	80 (4.9%)	43 (5.0%)
	Treatment duration, median days Rivaroxaban Enoxaparin/VKAs	182 (1-359) 181 (1-359)	183 (1-359) 182 (1-359)	184 (1-359) 183 (1-359)	184 (1-359) 183 (1-359)
	Proportion of patients with INR > 3.0 < 2.0 2.0 to 3.0	20.6% 17.3% 62.1%	19.5% 17.8% 62.6%	17.7% 17.0% 65.3%	17.6% 19.3% 63.1%
Results		BMI<25 (n=2,481)	BMI ≥ 25-30 (n=3,258)	BMI ≥ 30-35 (n=1,630)	BMI ≥ 35 (n=861)
	Recurrent VTE Rivaroxaban Enoxaparin/VKA	28/1,266 (2.2%) 30/1,215 (2.5%)	35/1,608 (2.2%) 41/1,650 (2.5%)	10/825 (1.2%) 14/805 (1.7%)	13/427 (3.0%) 9/434 (2.1%)
	Hazard ratio (95% CI)	0.92 (0.54 to 1.57)	0.82 (0.52 to 1.29)	0.70 (0.31 to 1.57)	1.45 (0.62 to 3.39)
	Major bleeding Rivaroxaban Enoxaparin/VKA	15/1,257 (1.2%) 25/1,214 (2.1%)	18/1,603 (1.1%) 30/1,643 (1.8%)	2/822 (0.2%) 8/803 (1.0%)	5/426 (1.2%) 7/432 (1.6%)
	Hazard ratio (95% CI)	0.56 (0.30 to 1.06)	0.60 (0.34 to 1.08)	0.27 (0.06 to 1.28)	0.71 (0.22 to 2.24)
	No association between BMI and recurrent VTE was found for rivaroxaban group or enoxaparin/VKA group. No association between BMI and major bleeding was found for rivaroxaban group or enoxaparin/VKA group.
Study Author Conclusions	The fixed-dose regimen of rivaroxaban 15 mg twice daily for the first 21 days, followed by 20 mg once daily without any dose adjustments, was not associated with either an increased risk of major bleeding in patients with a low BMI or an increased risk of recurrent VTE in patients with a high BMI.
InpharmD Researcher Critique	The study did not measure any changes of BMI during the intervention. Also, other co-morbidities may have masked the effects of BMI on the risk of major bleeding and recurrent VTE. This study was a post-hoc analysis of two trials and did not attempt to adjust for confounders when merging groups. Attempts to stratify based on the treatment period of 3, 6, or 12 months was also not mentioned meaning the results represent quite a number of different individual therapeutic strategies.

References:

Di Nisio M, Vedovati MC, Riera-Mestre A, Prins MH, Mueller K, Cohen AT, et al. Treatment of venous thromboembolism with rivaroxaban in relation to body weight: a sub-analysis of the EINSTEIN DVT/PE studies. Thromb Haemost. 2016;116(4):739–46. doi: 10.1160/TH16-02-0087

Investigation of Direct-Acting Oral Anticoagulants and the Incidence of Venous Thromboembolism in Patients Weighing 120 kg Compared to Patients Weighing
Design	Retrospective database analysis and chart review of patients receiving a DOAC within Veterans Integrated Service Network (VISN) N=1,196
Objective	To identify if a difference exists in incidence of recurrent thromboembolic events in patients receiving a direct oral anticoagulant (DOAC) for the indication of venous thromboembolism (VTE) weighing ≥ 120 kg compared to patients weighing <120 kg
Study Groups	Patients Weighing ≥ 120 kg (n=133) Patients Weighing <120 kg (n=1,063)
Inclusion Criteria	All adult Veterans older than the age of 18 who were treated with rivaroxaban, dabigatran, or apixaban for the treatment of a VTE within VISN 8 of the VHA system
Exclusion Criteria	Patients who received edoxaban; patients non-compliant with DOAC therapy (noncompliance was defined as more than 30 days past where refills were due)
Methods	A retrospective database analysis was conducted on patients taking either apixaban, dabigatran, or rivaroxaban for treatment of VTE from the Veterans Integrated Service Network 8, which consists of seven healthcare systems in Florida, Georgia, and Puerto Rico. Fisher’s exact tests were used to evaluate differences in VTEs between patients weighing ≥ 120 kg compared to patients <120 kg.
Duration	January 2012 and June 2017
Outcome Measures	Primary: incidence of recurrent VTE Secondary: differences among DOACs (dabigatran, rivaroxaban, apixaban) in the incidence of VTE recurrence
Baseline Characteristics		≥120 kg (n=133)	<120 kg (n=1,063)	P-value
	Age, years	62.0 ± 12.0	69.0 ± 13.0	<0.01
	Male	94.7%	93.3%	0.53
	BMI, kg/m²	41.2 ± 5.6	28.7 ± 5.0	<0.01
	Weight, kg	134.9 ± 14.9	89.6 ± 16.4	<0.01
	White	80.5%	81.7%	0.69
	DOAC agent prescribed Apixaban Dabigatran Rivaroxaban	17 (12.8%) 39 (29.3%) 77 (57.9%)	210 (19.8%) 314 (29.5%) 539 (50.7%)	0.12
	Duration on DOAC, days	241.6 ± 269.9	212.2 ± 228.6	0.17
Results		≥120 kg (n=133)	<120 kg (n=1,063)	P-value
	Overall VTE recurrences With apixaban With dabigatran With rivaroxaban	1 (0.8%) 0 1/39 (2.6%) 0	12 (1.1%) 3/210 (1.4%) 3/314 (0.9%) 6/539 (1.1%)	0.69 1.00 0.38 1.00
	Upon chart review of primary outcome events, 3 patients (all <120 kg) with a documented recurrent VTE were noted to have recently missed doses of DOAC therapy at the time of VTE. If these events are excluded, the incidence of VTE between the weight groups would both be 0.8% (odds ratio 0.89; 95% confidence interval 0.11 to 7.06; P=0.91)
Adverse Events	Not studied
Study Author Conclusions	This study found no difference in VTE recurrence in patients weighing ≥ 120 kg compared to patients <120 kg with few events in either group.
InpharmD Researcher Critique	Limitations include the differences in the baseline characteristics between the study groups; patients weighing ≥ 120 kg were younger than patients weighing < 120 kg (mean age: 62 vs 69 years, respectively), and increasing age is a risk factor for VTE. The low incidence of VTE recurrence requires a large sample size that could not be met with the current Veterans Affairs patient pool; therefore, the study was underpowered.

References:

Aloi KG, Fierro JJ, Stein BJ, Lynch SM, Shapiro RJ. Investigation of Direct-Acting Oral Anticoagulants and the Incidence of Venous Thromboembolism in Patients Weighing ≥120 kg Compared to Patients Weighing <120 kg [published online ahead of print, 2019 Jun 25]. J Pharm Pract. 2019;897190019854578. doi:10.1177/0897190019854578

Safety and efficacy of apixaban, dabigatran and rivaroxaban in obese and morbidly obese patients with heart failure and atrial fibrillation: A real-world analysis
Design	Single-center retrospective observational study N= 883
Objective	To study the comparative safety and efficacy of direct-acting oral anticoagulants (DOACs) in obese and morbidly obese patients with atrial fibrillation (AF) or flutter, and concomitant congestive heart failure (HF)
Study Groups	Apixaban (n= 155) Rivaroxaban (n= 335) Dabigatran (n= 393)
Inclusion Criteria	Patients aged ≥18 years with non-valvular AF and/or atrial flutter and concurrent HF, on apixaban, dabigatran, or rivaroxaban
Exclusion Criteria	Patients with alternative indication for anticoagulation other than AF, planned AF ablation, history of infective endocarditis, or end-stage renal disease
Methods	Patients with ICD-9 code of atrial fibrillation or atrial flutter, and congestive heart failure on a DOAC were followed for a median 12.5 months. Obesity was defined as BMI ≥30 and<40 kg/m2, and morbid obesity as BMI ≥40 kg/m2.
Duration	January 1, 2011 to September 1, 2015
Outcome Measures	Primary: Safety (composite of intracranial-hemorrhage, gastrointestinal-bleeds, hemorrhagic-stroke, and other bleeds) Secondary: Efficacy (composite of ischemic-stroke and systemic-embolism)
		Obese (BMI ≥30 and<40 kg/m2)				Morbidly obese (BMI ≥40 kg/m2)
Baseline Characteristics		Rivaroxaban (n= 238)	Apixaban (n= 101)	Dabigatran (n= 275)		Rivaroxaban (n= 97)	Apixaban (n= 54)	Dabigatran (n= 118)
	Age, years (IQR)	70 (62, 79)	78.4 (67.6, 87.1)	71 (63, 79)		62 (55, 71)	67.4 (58, 76.1)	65.5 (57, 74)
	Female	111 (46.6%)	48 (47.5%)	134 (48.7%)		52 (53.6%)	32 (59.3%)	74 (62.7%)
	BMI (IQR)	33.4 (31.7, 36.0)	33.7 (31.8, 36.3)	33.4 (31.5, 35.9)		45.7 (42.9, 49.9)	46.1 (42.3, 50.4)	45.3 (41.9, 50.2)
	Comorbidities Heart failure reduced ejection fraction Prior Myocardial Infarction Prior Cerebrovascular disease Diabetes Mellitus Diabetic Complications	82 (41%) 37 (15.6%) 21 (8.8%) 104 (43.7%) 46 (19.3%)	38 (48.1%) 21 (20.8%) 20 (19.8%) 48 (47.5%) 16 (15.8%)	87 (38.5%) 59 (21.5%) 40 (14.6%) 121 (44.0%) 33 (12.0%)		34 (41.0%) 14 (14.4%) 5 (5.2%) 46 (47.4%) 21 (21.7%)	18 (40.9%) 9 (16.7%) 5 (9.3%) 22 (40.7%) 11 (20.4%)	32 (32.3%) 11 (9.3%) 9 (7.6%) 52 (44.1%) 18 (15.3%)
	Abbreviations: BMI, body mass index; IQR, interquartile range Among morbidly obese (BMI ≥ 40 kg/m²) users, median Charlson comorbidity scores were 3 for rivaroxaban, 5 for apixaban, and 3 for dabigatran. Digoxin use ranged from 25.8% (rivaroxaban) to 44.9% (dabigatran). Use of antiplatelets, NSAIDs, and amiodarone was similar across groups. Reduced-dose DOAC use ranged from 26.2% to 30.2%, with higher proportions in dabigatran users.
		Obese (BMI ≥30 and<40 kg/m2)				Morbidly obese (BMI ≥40 kg/m2)
Results		Rivaroxaban (n= 238)	Apixaban (n= 101)	Dabigatran (n= 275)	p-value	Rivaroxaban (n= 97)	Apixaban (n= 54)	Dabigatran (n= 118)	p-value
	Efficacy Outcomes	7 (2.9%)	6 (5.9%)	25 (9.1%)	0.016	9 (9.3%)	2 (3.7%)	10 (8.5%)	0.44
	Ischemic Stroke	7 (2.9%)	6 (5.9%)	24 (8.7%)	0.023	9 (9.3%)	2 (3.7%)	10 (8.5%)	0.44
	Systemic Embolization	0 (0.0%)	0 (0.0%)	1 (0.4%)	0.54	0 (0.0%)	0 (0.0%)	0 (0.0%)	1
	Safety Outcomes	61 (25.6%)	7 (6.9%)	96 (34.9%)	<0.001	15 (15.5%)	6 (11.1%)	37 (31.4%)	0.01
	Hemorrhagic Stroke	5 (2.1%)	1 (1.0%)	5 (1.8%)	0.78	1 (1.0%)	0 (0.0%)	3 (2.5%)	0.4
	Intracranial Hemorrhage	1 (0.4%)	0 (0.0%)	2 (0.7%)	0.66	0 (0.0%)	0 (0.0%)	0 (0.0%)	1
	Gastrointestinal Bleeding	33 (13.9%)	4 (4.0%)	54 (19.6%)	0.0007	8 (8.3%)	5 (9.3%)	21 (17.8%)	0.13
	Other Major Bleeding	22 (9.2%)	2 (2.0%)	35 (12.7%)	0.007	6 (6.2%)	1 (1.9%)	13 (11.0%)	0.088
	All-cause mortality	16 (6.7%)	6 (5.9%)	46 (16.7%)	0.0003	6 (6.2%)	4 (7.4%)	19 (16.1%)	0.044
	Kaplan-Meier (KM) analysis showed no significant differences in efficacy outcomes among obese (p= 0.2) or morbidly obese (p= 0.2) patients. All-cause mortality was highest in dabigatran users for both obese (16.7% vs. 6.7% rivaroxaban vs. 5.9% apixaban, p = 0.0003) and morbidly obese patients (16.1% vs. 6.2% rivaroxaban vs. 7.4% apixaban, p= 0.04), but KM curves over a median 12.5-month follow-up showed no statistically significant differences between the three DOACs.
Adverse Events	Kaplan-Meier analysis showed significant safety differences among obese patients (p= 0.008) but not morbidly obese patients. In Cox regression, apixaban had lower risk of bleeding than dabigatran (hazard ratio [HR] 0.37, p= 0.02) and rivaroxaban (HR 0.29, p= 0.004), remaining significant after adjustment for comorbidities, medication use, and DOAC dose. See above for further details regarding adverse events.
Study Author Conclusions	In obese patients with congestive heart failure and atrial fibrillation or atrial flutter on DOACs, apixaban has the most favorable safety profile compared to rivaroxaban and dabigatran.
Critique	The study provides valuable insights into the safety and efficacy of DOACs in obese and morbidly obese patients, a population underrepresented in clinical trials. However, the retrospective design and single-center setting may limit the generalizability of the findings.

References:

Chugh Y, Gupta K, Krishna HB, et al. Safety and efficacy of apixaban, dabigatran and rivaroxaban in obese and morbidly obese patients with heart failure and atrial fibrillation: A real-world analysis. Pacing Clin Electrophysiol. 2023;46(1):50-58. doi:10.1111/pace.14623