Abstract
Background:
Direct anticoagulants (DOACs), apixaban and rivaroxaban, are used for the treatment of venous thromboembolism (VTE) and have product labeling to dose-reduce for extended-phase secondary prevention of VTE. The objective of this study was to better understand prescribing patterns of DOACs among a broad cohort of clinicians.
Methods:
In this secondary analysis of a survey deployed to two distinct populations of clinicians, thrombosis specialists and primary care physicians (PCPs), we used descriptive statistics, Fisher’s exact test, and regression to explore relationships between respondent demographics and prescribing behaviors.
Results:
Among 336 respondents, 12 % were pharmacists, 23 % were PCPs, and 65 % were specialists. Most (59 %) practiced in an academic setting, and 18 % practiced outside of North America. When considering provider type, 88 % of pharmacists, 78 % of specialists, and 61 % of PCPs indicated that they dose-reduce DOACs for extended-phase therapy for the secondary prevention of VTE (p-value = 0.002). PCPs were most likely to engage in temporary dose-escalation (p-value < 0.001) when presented with various scenarios of increased risk. Providers who prescribed DOACs in >250 patients were also more likely to dose-reduce (aOR 2.41, 1.24–4.82 95 % CI, p-value = 0.01). Pharmacists overwhelmingly preferred prescribing apixaban, while PCPs and specialists were more balanced between prescribing apixaban and rivaroxaban (p-value < 0.001).
Conclusion:
Most clinicians elect to dose-reduce DOACs during the extended phase of anticoagulation. Provider type and number of patients correlated with prescribing practices. These findings identify opportunities to advance clinician education surrounding dose-reduction when clinically indicated.
Keywords: Venous thromboembolism, Direct oral anticoagulant, Dose-reduction, Extended-phase treatment, Apixaban, Rivaroxaban
1. Introduction
Anticoagulation is the mainstay of therapy for venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). The treatment phase for acute VTE has a duration of 3–6 months. Anticoagulation is recommended to be continued beyond this time when the risk of recurrent thrombosis is assessed to be high. This continuation is referred to as extended-phase anticoagulation [1]. Apixaban and rivaroxaban are direct oral anticoagulants (DOACs) approved for the treatment and prevention of VTE [2,3]. DOACs have been studied for the secondary prevention of recurrent VTE for whom the continuation of anticoagulants is indicated [4,5]. When compared with standard dosing (apixaban 5 mg BID, rivaroxaban 20 mg daily) the reduced doses of apixaban (2.5 mg BID) and rivaroxaban (10 mg daily) for extended-phase anticoagulation are equally safe and effective in preventing recurrent VTE with a trend towards fewer bleeding events [6]. Among patients for whom dose-reduction is elected, clinical practice can include escalation to treatment-phase dosing during a period of high-risk for thrombosis.
In our prior work we reported on clinicians’ perceptions and prescribing patterns of reduced-dose DOACs for extended-phase VTE prevention among two provider populations: thrombosis specialists and primary care providers (PCP) [7,8]. For this investigation, we combine the results of both studies to better understand and characterize DOAC prescribing behaviors of all surveyed clinicians.
2. Methods
This work was conducted by members of the Venous ThromboEmbolism Network U.S. (VENUS) Subcommittee on Venous Thromboembolism Treatment and Anticoagulation Management. VENUS is a collaborative working group sponsored by the Anticoagulation Forum, National Blood Clot Alliance, American Society of Hematology Foundation, Hemostasis and Thrombosis Research Society and Versiti. Survey content was developed and refined by members of the VENUS subcommittee to contain 21 questions. Survey questions probed prescribing behaviors for dose-reduction of DOACs for extended phase VTE treatment (hereafter referred to as ‘dose-reduce’ or ‘dose-reduction’), including frequency, risk factors, escalation to treatment-phase dosing, and other preferences.
The methodology and results of the initial survey results among attendees of the International Society of Thrombosis and Haemostasis (ISTH) 2021 meeting and subsequently, members of the American College of Physicians, and the U.S. Veterans Administration (VA) anticoagulation services were formerly published [7,8]. Here we combine and report the results of all respondents using descriptive statistics, Fisher’s Exact Test, and logistic regression. All analyses were conducted with R4.2.2. The Intermountain Health Institutional Review Board granted a waiver of informed consent (Reference #1051695).
3. Results
Combining studies resulted in 336 individuals divided into three provider types, pharmacists (12 %), PCPs (23 %), and specialists (65 %). All pharmacists indicated that they were mid-level providers that specialized in anticoagulation and were primarily associated with the VA healthcare system. Over one third of specialists indicated specialization in thrombosis, while nearly one-quarter specialized in either hematology-oncology (23 %) or hematology alone (22 %). Most specialists (68 %) were associated with academic teaching hospitals. PCPs were largely associated with academic teaching hospitals (45 %), followed by private practice (26 %) (Table 1).
Table 1.
Respondent demographics by provider type.
| Attribute | Pharmacist, n = 40 | Primary care, n = 76 | Specialist, n = 220 | All, n = 336 |
|---|---|---|---|---|
|
| ||||
| Present status | ||||
| Unknown | 0 (0.0 %) | 0 (0.0 %) | 1 (0.5 %) | 1 (0.3 %) |
| Trainee (student, resident, fellow) | 0 (0.0 %) | 4 (5.3 %) | 20 (9.1 %) | 24 (7.1 %) |
| Nurse practitioner/physician assistant/mid-level provider | 40 (100.0 %) | 5 (6.6 %) | 39 (17.7 %) | 84 (25.0 %) |
| Attending physician | 0 (0.0 %) | 67 (88.2 %) | 160 (72.7 %) | 227 (67.6 %) |
| Specialtya | ||||
| General hematology | 0 (0.0 %) | 0 (0.0 %) | 48 (21.8 %) | 48 (14.3 %) |
| Medical oncology | 0 (0.0 %) | 0 (0.0 %) | 9 (4.1 %) | 9 (2.7 %) |
| Hematology oncology | 0 (0.0 %) | 0 (0.0 %) | 51 (23.2 %) | 51 (15.2 %) |
| Hematology thrombosis | 0 (0.0 %) | 5 (6.6 %) | 80 (36.4 %) | 85 (25.3 %) |
| Vascular medicine | 0 (0.0 %) | 3 (3.9 %) | 12 (5.5 %) | 15 (4.5 %) |
| Cardiology | 0 (0.0 %) | 1 (1.3 %) | 17 (7.7 %) | 18 (5.4 %) |
| Pulmonary, critical care, intensivist | 0 (0.0 %) | 1 (1.3 %) | 4 (1.8 %) | 5 (1.5 %) |
| Internal medicine, primary care | 0 (0.0 %) | 76 (100.0 %) | 0 (0.0 %) | 76 (22.6 %) |
| Anticoagulation | 40 (100.0 %) | 0 (0.0 %) | 0 (0.0 %) | 40 (11.9 %) |
| Multiple | 0 (0.0 %) | 10 (13.2 %) | 26 (11.8 %) | 36 (10.7 %) |
| Setting | ||||
| Unknown | 0 (0.0 %) | 0 (0.0 %) | 0 (0.0 %) | 0 (0.0 %) |
| Private practice | 0 (0.0 %) | 20 (26.3 %) | 14 (6.4 %) | 34 (10.1 %) |
| Private non-teaching hospital | 0 (0.0 %) | 4 (5.3 %) | 8 (3.6 %) | 12 (3.6 %) |
| Academic nonteaching hospital | 0 (0.0 %) | 3 (3.9 %) | 10 (4.5 %) | 13 (3.9 %) |
| Academic teaching hospital | 2 (5.0 %) | 34 (44.7 %) | 149 (67.7 %) | 185 (55.1 %) |
| Veterans affairs | 38 (95.0 %) | 3 (3.9 %) | 32 (14.5 %) | 73 (21.7 %) |
| Other | 0 (0.0 %) | 12 (15.8 %) | 7 (3.2 %) | 19 (5.7 %) |
| Percent of clinical time is outpatient care | ||||
| I provide no outpatient care | 0 (0.0 %) | 0 (0.0 %) | 0 (0.0 %) | 0 (0.0 %) |
| <20 % | 2 (5.0 %) | 11 (14.5 %) | 7 (3.2 %) | 20 (6.0 %) |
| 20–49 % | 1 (2.5 %) | 13 (17.1 %) | 31 (14.1 %) | 45 (13.4 %) |
| 50–79 % | 1 (2.5 %) | 11 (14.5 %) | 80 (36.4 %) | 92 (27.4 %) |
| 80–99 % | 7 (17.5 %) | 9 (11.8 %) | 66 (30.0 %) | 82 (24.4 %) |
| 100 % | 29 (72.5 %) | 31 (40.8 %) | 36 (16.4 %) | 96 (28.6 %) |
| Years in practice | ||||
| <5 years | 5 (12.5 %) | 12 (15.8 %) | 50 (22.7 %) | 67 (19.9 %) |
| 5–10 years | 9 (22.5 %) | 11 (14.5 %) | 56 (25.5 %) | 76 (22.6 %) |
| 11–15 years | 13 (32.5 %) | 11 (14.5 %) | 36 (16.4 %) | 60 (17.9 %) |
| 16–20 years | 2 (5.0 %) | 10 (13.2 %) | 16 (7.3 %) | 28 (8.3 %) |
| 21–25 years | 3 (7.5 %) | 6 (7.9 %) | 28 (12.7 %) | 37 (11.0 %) |
| 26–30 years | 6 (15.0 %) | 7 (9.2 %) | 12 (5.5 %) | 25 (7.4 %) |
| 31–35 years | 2 (5.0 %) | 11 (14.5 %) | 7 (3.2 %) | 20 (6.0 %) |
| >35 years | 0 (0.0 %) | 8 (10.5 %) | 15 (6.8 %) | 23 (6.8 %) |
| Number of patients where you are involved in DOAC prescriptions | ||||
| <50 | 2 (5.0 %) | 23 (30.3 %) | 27 (12.3 %) | 52 (15.5 %) |
| 51–100 | 1 (2.5 %) | 22 (28.9 %) | 59 (26.8 %) | 82 (24.4 %) |
| 101–250 | 1 (2.5 %) | 15 (19.7 %) | 48 (21.8 %) | 64 (19.0 %) |
| 251–500 | 11 (27.5 %) | 6 (7.9 %) | 40 (18.2 %) | 57 (17.0 %) |
| 500–1000 | 11 (27.5 %) | 5 (6.6 %) | 29 (13.2 %) | 45 (13.4 %) |
| >1000 | 14 (35.0 %) | 5 (6.6 %) | 17 (7.7 %) | 36 (10.7 %) |
| Protocol in place | 8 (20.0 %) | 3 (3.9 %) | 18 (8.2 %) | 29 (8.6 %) |
| World region | ||||
| Unknown/other | 0 (0.0 %) | 4 (5.3 %) | 16 (7.3 %) | 20 (6.0 %) |
| Europe | 0 (0.0 %) | 4 (5.3 %) | 21 (9.5 %) | 25 (7.4 %) |
| Central and South America | 0 (0.0 %) | 7 (9.2 %) | 8 (3.6 %) | 15 (4.5 %) |
| North America | 40 (100.0 %) | 61 (80.3 %) | 175 (79.5 %) | 276 (82.1 %) |
| US region | ||||
| Midwest | 18 (45.0 %) | 5 (6.6 %) | 50 (22.7 %) | 73 (21.7 %) |
| Mountain West | 3 (7.5 %) | 20 (26.3 %) | 20 (9.1 %) | 43 (12.8 %) |
| Northeast | 3 (7.5 %) | 15 (19.7 %) | 45 (20.5 %) | 63 (18.8 %) |
| Northwest | 3 (7.5 %) | 1 (1.3 %) | 6 (2.7 %) | 10 (3.0 %) |
| South | 2 (5.0 %) | 0 (0.0 %) | 0 (0.0 %) | 2 (0.6 %) |
| Southeast | 8 (20.0 %) | 1 (1.3 %) | 19 (8.6 %) | 28 (8.3 %) |
| Southwest | 1 (2.5 %) | 3 (3.9 %) | 4 (1.8 %) | 8 (2.4 %) |
| West Coast | 1 (2.5 %) | 10 (13.2 %) | 13 (5.9 %) | 24 (7.1 %) |
Respondents could select more than one specialty.
Most pharmacists (90 %), indicated that they spent over 80 % of their clinical time in outpatient care while PCP’s and specialist’s time was more evenly distributed between inpatient and outpatient responsibilities. All time frames of years in practice were represented across all three groups with pharmacists and specialists trending slightly towards fewer years in practice. Ninety percent of pharmacists were involved in monitoring DOAC prescriptions in 250 or more patients, while 79 % of PCPs cared for fewer than 250 DOAC-anticoagulated patients. Only 8.6 % of respondents reported that their institution had a protocol in place for DOAC dose-reduction. The majority (82 %) of respondents were from North America.
Overall, three quarters indicated that they chose to dose-reduce DOACs for extended-phase treatment of VTE. Among pharmacists, 88 % indicated that they dose-reduce, compared with 61 % of PCPs and 78 % of specialists (p-value = 0.002). Forty percent of respondents reported that they ‘usually’ (50–100 % of the time) elected dose-reduction. Most pharmacists (73 %), specialists (73 %), and to a lesser degree, PCPs (57 %), reported electing dose-reduction either ‘sometimes’ (25–50 % of the time), ‘usually’, or ‘always’ (100 % of the time) (p-value = 0.013) (Table 2).
Table 2.
Prescribing preferences by provider type.
| Attribute | Pharmacist, n = 40 | Primary care, n = 76 | Specialist, n = 220 | p-Value | All, n = 336 |
|---|---|---|---|---|---|
|
| |||||
| Dose-reduce | 35 (87.5 %) | 46 (60.5 %) | 172 (78.2 %) | 0.002 | 253 (75.3 %) |
| How often | 0.013 | ||||
| Never (0 % of the time) | 5 (12.5 %) | 30 (39.5 %) | 49 (22.3 %) | 84 (25.0 %) | |
| Rarely (between 0 and 25 %) | 6 (15.0 %) | 3 (3.9 %) | 11 (5.0 %) | 20 (6.0 %) | |
| Sometimes (25–50 % of the time) | 9 (22.5 %) | 16 (21.1 %) | 66 (30.0 %) | 91 (27.1 %) | |
| Usually (between 50 and 100 %) | 19 (47.5 %) | 25 (32.9 %) | 90 (40.9 %) | 134 (39.9 %) | |
| Always (100 % of the time) | 1 (2.5 %) | 2 (2.6 %) | 4 (1.8 %) | 7 (2.1 %) | |
| Reasons to not dose-reduce | |||||
| Obesity | 35 (87.5 %) | 29 (38.2 %) | 122 (55.5 %) | <0.001 | 186 (55.4 %) |
| Cancer | 39 (97.5 %) | 57 (75.0 %) | 177 (80.5 %) | 0.005 | 273 (81.2 %) |
| Heritable thrombophilia | 35 (87.5 %) | 41 (53.9 %) | 96 (43.6 %) | <0.001 | 172 (51.2 %) |
| Recurrent VTE | 29 (72.5 %) | 60 (78.9 %) | 146 (66.4 %) | 0.108 | 235 (69.9 %) |
| Insurance coverage | 1 (2.5 %) | 11 (14.5 %) | 10 (4.5 %) | 0.012 | 22 (6.5 %) |
| Patient preference | 27 (67.5 %) | 28 (36.8 %) | 93 (42.3 %) | 0.005 | 148 (44.0 %) |
| Active smoking | 1 (2.5 %) | 21 (27.6 %) | 24 (10.9 %) | <0.001 | 46 (13.7 %) |
| Bedbound/immobile/sedentary | 16 (40.0 %) | 35 (46.1 %) | 65 (29.5 %) | 0.023 | 116 (34.5 %) |
| ECOG performance | 0 (0.0 %) | 5 (6.6 %) | 17 (7.7 %) | 0.181 | 22 (6.5 %) |
| Estrogen hormone therapy | 15 (37.5 %) | 23 (30.3 %) | 75 (34.1 %) | 0.717 | 113 (33.6 %) |
| Gestalt | 9 (22.5 %) | 18 (23.7 %) | 61 (27.7 %) | 0.719 | 88 (26.2 %) |
| Prior VTE while on therapy | 33 (82.5 %) | 53 (69.7 %) | 149 (67.7 %) | 0.170 | 235 (69.9 %) |
| Male | 0 (0.0 %) | 2 (2.6 %) | 17 (7.7 %) | 0.066 | 19 (5.7 %) |
| Age | 1 (2.5 %) | 5 (6.6 %) | 14 (6.4 %) | 0.738 | 20 (6.0 %) |
| Anti-phospholipid syndrome | 30 (75.0 %) | 37 (48.7 %) | 148 (67.3 %) | 0.005 | 215 (64.0 %) |
| Other | 1 (2.5 %) | 4 (5.3 %) | 13 (5.9 %) | 0.817 | 18 (5.4 %) |
| Conditions to consider dose-reduction | |||||
| Pulmonary embolism | 33 (82.5 %) | 30 (39.5 %) | 149 (67.7 %) | <0.001 | 212 (63.1 %) |
| Proximal DVT | 34 (85.0 %) | 33 (43.4 %) | 161 (73.2 %) | <0.001 | 228 (67.9 %) |
| Distal DVT | 36 (90.0 %) | 51 (67.1 %) | 172 (78.2 %) | 0.017 | 259 (77.1 %) |
| Unusual site | 8 (20.0 %) | 20 (26.3 %) | 79 (35.9 %) | 0.072 | 107 (31.8 %) |
| History of bleeding | 33 (82.5 %) | 66 (86.8 %) | 183 (83.2 %) | 0.770 | 282 (83.9 %) |
| Concurrent use of antiplatelet therapy | 25 (62.5 %) | 54 (71.1 %) | 156 (70.9 %) | 0.537 | 235 (69.9 %) |
| Engage in escalation to treatment-phase dosing | 5 (12.5 %) | 39 (51.3 %) | 81 (36.8 %) | <0.001 | 125 (37.2 %) |
| Situations to escalate to treatment-phase dosing | |||||
| Post surgery | 2 (5.0 %) | 32 (42.1 %) | 61 (27.7 %) | <0.001 | 95 (28.3 %) |
| Hospitalization | 0 (0.0 %) | 23 (30.3 %) | 37 (16.8 %) | <0.001 | 60 (17.9 %) |
| Hormone use | 1 (2.5 %) | 15 (19.7 %) | 35 (15.9 %) | 0.026 | 51 (15.2 %) |
| Pregnancy/post partum | 1 (2.5 %) | 11 (14.5 %) | 33 (15.0 %) | 0.069 | 45 (13.4 %) |
| Cancer if original etiology for VTE was not cancer | 5 (12.5 %) | 32 (42.1 %) | 63 (28.6 %) | 0.003 | 100 (29.8 %) |
| Bedbound/immobile/sedentary | 2 (5.0 %) | 27 (35.5 %) | 41 (18.6 %) | <0.001 | 70 (20.8 %) |
| Long travel | 1 (2.5 %) | 20 (26.3 %) | 25 (11.4 %) | 0.001 | 46 (13.7 %) |
| DOAC prescribed most often | <0.001 | ||||
| Rivaroxaban | 0 (0.0 %) | 14 (18.4 %) | 28 (12.7 %) | 42 (12.5 %) | |
| Prescribe apixaban and rivaroxaban equally | 3 (7.5 %) | 19 (25.0 %) | 65 (29.5 %) | 87 (25.9 %) | |
| Apixaban | 35 (87.5 %) | 43 (56.6 %) | 127 (57.7 %) | 205 (61.0 %) | |
| Which do you dose-reduce | <0.001 | ||||
| Rivaroxaban | 0 (0.0 %) | 8 (10.5 %) | 8 (3.6 %) | 16 (4.8 %) | |
| Both | 40 (100.0 %) | 41 (53.9 %) | 175 (79.5 %) | 256 (76.2 %) | |
| Apixaban | 0 (0.0 %) | 6 (7.9 %) | 17 (7.7 %) | 23 (6.8 %) | |
| Neither | 0 (0.0 %) | 20 (26.3 %) | 20 (9.1 %) | 40 (11.9 %) | |
| Unknown | 0 (0.0 %) | 1 (1.3 %) | 0 (0.0 %) | 1 (0.3 %) | |
| More comfortable reducing one medication over the other | 2 (5.0 %) | 16 (21.1 %) | 30 (13.6 %) | 0.060 | 48 (14.3 %) |
| Which is more comfortable to decrease | 0.105 | ||||
| Rivaroxaban | 0 (0.0 %) | 6 (7.9 %) | 6 (2.7 %) | 12 (3.6 %) | |
| Apixaban | 2 (5.0 %) | 10 (13.2 %) | 24 (10.9 %) | 36 (10.7 %) | |
| Not applicable | 38 (95.0 %) | 60 (78.9 %) | 190 (86.4 %) | 288 (85.7 %) | |
| Timing affects decision | 2 (5.0 %) | 15 (19.7 %) | 36 (16.4 %) | 0.088 | 53 (15.8 %) |
When asked about reasons to not elect dose-reduction, responses differed by provider type. Pharmacists described refraining from dose-reduction in patients with obesity, cancer, heritable thrombophilia, and based on patient preference. However, PCPs refrained from dose-reduction for reasons of insurance coverage, active smoking, and immobility. Specialists and pharmacists both selected antiphospholipid syndrome as a reason to refrain from dose-reduction at higher rates than PCPs. When considering indications for continued anticoagulation with dose-reduction, pharmacists had the highest response rates for pulmonary embolism, proximal DVT, and distal DVT.
Fifty-one percent of PCPs engaged in escalation to treatment-phase dosing while far fewer specialists (37 %) and pharmacists did so (13 %) (p-value < 0.001). PCPs had the highest rates of escalation to treatment-phase dosing for nearly all clinical scenarios of increased thrombosis risk with an absolute difference of 14 % to 17 % for post-surgery, hospitalization, cancer (if original etiology for VTE was not cancer), bedbound/immobile/sedentary, and long travel. Specialists and PCP had similar rates of temporary dose escalation for hormone use and pregnancy/postpartum.
Sixty-one percent of all providers preferred prescribing apixaban over rivaroxaban. Few North American providers (6.2 %) preferred rivaroxaban while over half (58 %) of the respondents outside North America preferred rivaroxaban (p-value < 0.001). Few respondents (14 %), indicated that they were more comfortable with prescribing one medication over the other.
Unadjusted odds ratios showed that those most likely to dose-reduce were attending physicians, specialists in hematology, other specialties, or multiple specialties (respondents could select one or more specialties), those practicing at an academic hospital, and those treating >250 patients with DOAC prescriptions. Adjusted analyses showed the same groups engaged in dose-reduction, attending physicians (3.58 adjusted odds ratio [aOR], 1.3–10.5 95 % confidence interval [CI], p-value = 0.018), hematology thrombosis specialists (3.5 aOR, 1.3–9.9 95%CI, p-value = 0.016), multiple specialties (18.1 aOR, 4.0–137 95 % CI, p-value = 0.001), and those treating >250 patients with DOACs (2.4 aOR, 1.2–4.8 95 % CI, p-value = 0.011).
4. Discussion
To our knowledge, this is the largest survey, distributed to two distinct populations, aimed at understanding clinician prescribing behaviors when considering dose-reduction of DOACs for extended-phase treatment of VTE. In our prior work we reported on each target group separately and within each clinician type we leveraged unsupervised machine learning to discover nuanced differences within these groups [7,8]. These data now combined permit a better understanding of the broader landscape of DOAC prescribing behaviors across the differing groups. Our cohort included a broad range of clinicians from varying levels of licensure, specialties, practice settings, geographical areas, and years in practice.
Our principal finding is that most clinicians elect to dose-reduce DOACs for the extended-phase treatment of VTE, independent of specialty. We also identified that providers who treat >250 patients with DOACs were more likely to dose-reduce. Although pharmacists and specialists had the highest rate of dose-reduction, pharmacists consistently had higher rates for reasons to not dose-reduce. Consistent with the high rate of dose-reduction, primary care providers consistently had the lowest rates for conditions to consider for dose-reduction. Additionally, PCPs had the highest rates of reporting that they engaged in escalation to treatment-phase dosing and had the highest rates for situations where they would elect to escalate dosing.
A key outcome of this study is that PCPs and specialists overwhelmingly indicated that there are no protocols in place at their institutions to inform decision-making surrounding DOAC dose-reduction. While considerably more frequent than physicians, only 20 % of pharmacists reported access to DOAC dose-reduction protocols, which reflects findings from a similar study [9]. This observation reflects a large gap in VTE care and an opportunity to implement guidance. Protocolization and anticoagulation stewardship efforts at the VA improved DOAC prescribing practices and patient outcomes [10]. The current practice at the VA employs an innovative system where outpatient pharmacists manage anticoagulation therapy. Additionally, pharmacists at the VA may orchestrate at the regional level by implementing evidence-based practices and protocols. This unique system may help explain why pharmacists had high rates for electing to dose-reduce while also having high rates for options both for and against dose-reduction.
A limitation of this work is that it was a self-report survey which may suffer from recall or social desirability bias. With this understanding, we did not ask respondents about clinical outcomes. The number needed to treat to avoid one major or clinically relevant bleeding event when comparing full-dose to reduced-dose regimens in extended treatment of VTE is approximately 100 patients every year [10]. In our study, we estimated that nearly 134,000 patients were being treated by survey respondents. Of those potential patients, nearly 21,675 were treated by respondents who did not dose-reduce and reported no protocols at their institution for dose-reduction strategies. Having protocols in place could reduce major or clinically relevant bleeding in approximately 216 patients treated by survey respondents alone. Our results highlight the need for supporting anticoagulation stewardship, enhancing education, providing protocols, and implementing various types of interventions among those prescribing anticoagulants to encourage best practices for extended phase treatment of VTE.
5. Conclusion
In conclusion, we found that most clinicians report that they elect to dose-reduce DOACs for extended-phase anticoagulation therapy for the prevention of recurrent VTE. We compared prescribing behaviors among different provider types and identified those who are mostly likely to dose-reduce. Further work calls for identifying and implementing approaches that will lead to increased awareness and desirable DOAC prescribing behaviors.
Footnotes
Declaration of competing interest
Conflicts of Interest: Danielle Groat, Lisa Bauman Kreuziger, Kristen Sanfilippo, Manila Gaddh, and Elizabeth Federici report nothing to disclose. Rachel Rosovsky discloses research funding to her institution from Janssen and BMS and that she has worked as a consultant for Janssen, BMS, Dova, Inari, and Penumbra. Karlyn Martin discloses research funding to her institution from Janssen. Scott Woller discloses research funding to his institution from Janssen.
CRediT authorship contribution statement
Danielle Groat: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Methodology, Investigation. Karlyn A. Martin: Writing – review & editing, Writing – original draft, Conceptualization. Rachel P. Rosovsky: Writing – review & editing, Writing – original draft, Conceptualization. Kristen M. Sanfilippo: Writing – review & editing, Writing – original draft, Conceptualization. Manila Gaddh: Writing – review & editing, Writing – original draft, Conceptualization. Lisa Baumann Kreuziger: Writing – review & editing, Writing – original draft, Conceptualization. Elizabeth Federici: Writing – review & editing, Writing – original draft, Conceptualization. Scott C. Woller: Writing – review & editing, Writing – original draft, Validation, Resources, Methodology, Investigation, Conceptualization.
Data availability
The Institutional Review Board (IRB) at Intermountain Health has approved that the data from this study (IRB# 1051695) would be reported in aggregate form only and that the original dataset would not be published. Parties interested in obtaining access to the original dataset must obtain approval through an Intermountain Health IRB study protocol amendment.
References
- [1].Stevens SM, Woller SC, Kreuziger LB, et al. , Antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report, Chest 160 (6) (2021) e545–e608, 10.1016/j.chest.2021.07.055. [DOI] [PubMed] [Google Scholar]
- [2].ELIQUIS, Package insert. https://packageinserts.bms.com/pi/pi_eliquis.pdf, April 2021. (Accessed 26 September 2024). [Google Scholar]
- [3].XARELTO Package Insert. http://www.janssenlabels.com/package-insert/productmonograph/prescribing-information/XARELTO-pi.pdf, February 2023. (Accessed 26 September 2024). [Google Scholar]
- [4].Agnelli G, Buller HR, Cohen A, et al. , Apixaban for extended treatment of venous thromboembolism, N. Engl. J. Med. 368 (8) (2013) 699–708, 10.1056/NEJMoa1207541. [DOI] [PubMed] [Google Scholar]
- [5].Weitz JI, Lensing AWA, Prins MH, et al. , Rivaroxaban or aspirin for extended treatment of venous thromboembolism, N. Engl. J. Med. 376 (13) (2017) 1211–1222, 10.1056/NEJMoa1700518. [DOI] [PubMed] [Google Scholar]
- [6].Vasanthamohan L, Boonyawat K, Chai-Adisaksopha C, Crowther M, Reduced-dose direct oral anticoagulants in the extended treatment of venous thromboembolism: a systematic review and meta-analysis, J. Thromb. Haemost. 16 (7) (2018) 1288–1295, 10.1111/jth.14156. [DOI] [PubMed] [Google Scholar]
- [7].Groat D, Martin KA, Rosovsky RP, et al. , Physician perceptions and use of reduced-dose direct oral anticoagulants for extended phase venous thromboembolism treatment, Res. Pract. Thromb. Haemost. 6 (4) (2022) e12740. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [8].Groat D, Martin KA, Rosovsky RP, et al. , Primary care clinicians’ prescribing patterns of reduced-dose direct oral anticoagulants for extended-phase venous thromboembolism treatment, J. Clin. Med. 13 (1) (2024) 96, 10.3390/jcm13010096. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [9].Triller DM, Wilson AS, Allen AL, et al. , Digital dashboards for direct oral anticoagulant surveillance, intervention and operational efficiency: uptake, obstacles, and opportunities, J. Thromb. Thrombolysis 57 (1) (2024) 107–116, 10.1007/s11239-023-02893-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [10].Barnes GD, Chen C, Holleman R, et al. , Pharmacist use of a population management dashboard for safe anticoagulant prescribing: evaluation of a nationwide implementation effort, J. Am. Heart Assoc. 13 (18) (2024) e035859, 10.1161/JAHA.124.035859. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The Institutional Review Board (IRB) at Intermountain Health has approved that the data from this study (IRB# 1051695) would be reported in aggregate form only and that the original dataset would not be published. Parties interested in obtaining access to the original dataset must obtain approval through an Intermountain Health IRB study protocol amendment.