Adolfo Llinás, Guillermo Bonilla, Cristina Suarez, Daniel Monsalvo, Juan Sebastián Sánchez-Osorio.
Response/Recommendation: Although there is some variation in adherence to the various venous thromboembolism (VTE) prevention regimes, most of the differences are explained by sociodemographic, socioeconomic, illness-related, patient-related, and medication-specific to health system-related factors. As a predictor of adherence, individual patient preferences present an opportunity to create value in person-centered care.
Strength of Recommendation: Limited.
Rationale: Adherence is the extent to which a person’s behavior coincides with medical or health advice. The greatest challenge in current therapeutics following the exponential development of the capacity of modern pharmacology is compliance1. Interestingly, patients who adhere to treatment, even when that treatment is a placebo, have better health outcomes than poorly adherent patients2.
The rigorous measurement of variation in adherence to VTE prophylaxis poses a challenging question that would require a comparison among mechanical, pharmacological, or combined protocols. With compression device and molecule representative of each kind, evaluated according to the route of administration, dosing frequency, and tolerance to the device or medication. Furthermore, the lack of a unified definition of adherence adds variation to the outcomes literature3. In the absence of such study, an approximation to the answer may be constructed from studies that report on some of the variables or with similar agents in different therapeutic situations.
The adherence to prophylaxis with outpatient portable compression devices in a rural population after total hip arthroplasty (THA) or total knee arthroplasty (TKA) was evaluated by Dietz et al.4. Compliance defined as 20 hours of use per day. In 115 joint arthroplasties, day one had the highest adherence post-discharge with an average usage of 13.2 hours/day. However, by day 14, usage fell to an average of 4.8 hours per day. Poor compliance was related to inconvenience due to heat or difficulty using the device.
Wilke et al.3, studied adherence rates in outpatient thrombosis prophylaxis with low-molecular-weight heparins (LMWH) after major orthopaedic surgery using a telephone survey and logistic regression models. They interviewed 1495 patients who had major orthopaedic surgery at 22 different clinics in Germany. Adherence rates ranged between 79% and 87%, depending on the indicator used for measurement. Non-adherent patients missed between 38% and 53% of their outpatient LMWH injections. If patients attended an outpatient rehabilitation program, the probability of their non-adherence increased substantially. Moreover, the non-adherent probability increased with each additional day between acute hospitalization and the start of rehabilitation (linking days). Non-adherence was lower for patients who feared thrombosis or who believed antithrombotic drugs to be the most critical measure in thromboprophylaxis.
Concerning contemporary regimes of oral prophylaxis, Carrothers et al.5, reported adherence rates to rivaroxaban of 83%, and Lebel et al.6, reported a rate of 98% to dabigatran, both requiring a single oral administration per day. The difference in compliance between full‑strength vs. low‑dose aspirin (ASA) for VTE prophylaxis following THA and TKA was measured by Hood et al.7, in 404 patients. They were able to reject the null hypothesis of decreased patient compliance utilizing full-strength 325 mg ASA twice daily following total joint arthroplasty (TJA) when compared to low-dose 81 mg twice daily. The VTE prophylactic regime was completed by 74% of the patients. The most cited reason for stopping ASA in both treatment groups was gastrointestinal issues (10.5% and 7%, respectively).
To address the question of the influence of administration route and dosage on adherence to extended thromboprophylaxis for THA or TKA, Moreno et al.8, undertook a cohort study of TJA patients who received pharmacological extended thromboprophylaxis. A telephonic questionnaire was applied 35 days after the day of the surgery with patients who omitted one or more doses of medication during the follow-up period classified as “non-adherent.” Five hundred and twenty patients were included: 153 received apixaban (oral 2.5 mg, twice a day), 155 enoxaparin (injectable 40 mg/sq, once a day), and 212 rivaroxaban (oral 10 mg, once a day). Patients receiving oral medication once a day were more compliant than those who received oral medication twice a day. Non-adherence rates were 3.2 and 9.2%, respectively (p = 0.033). No significant differences (p = 0.360) were found between oral once a day and injectable once a day medication. The number of daily doses prescribed was related to adherence to extended chemical prophylaxis, while the route of administration did not seem to have a significant impact.
Single or double daily dose anticoagulants that do not require monitoring have reduced the question of pharmacological adherence to the dichotomy of receiving the dose as prescribed or not. However, with vitamin K antagonists, monitoring of the therapeutic window is required. Ahmed et al.9, recently pointed out the additional challenge with warfarin in a study focusing on patient’s knowledge and adherence to anticoagulants and their effect on outcomes. The overall adherence to warfarin was 76.2%. However, only 20.45% were in the therapeutic range.
Patient preference may play a relevant role in adherence to VTE prophylaxis. Wong et al.10, analyzed patient preferences regarding pharmacologic VTE prophylaxis. Of the 227 patients, a majority (60.4%) preferred an oral medication, if equally effective to subcutaneous options. Dislike of needles (30.0%), and pain from injection (27.7%) were identified as rationales for their preference. Patients favoring subcutaneous administration (27.5%) identified a presumed faster onset of action (40.3%) as the primary reason for their preference. Patients with a preference for subcutaneous injections were less likely to refuse prophylaxis than patients who preferred an oral route of administration (37.5% vs. 51.3%, p < 0.0001).
Adherence to VTE prophylaxis; mechanical, pharmacological, or combined, requires management of the underlying factors that determine the output, which are diverse, and span sociodemographic, socioeconomic, illness-related, patient-related, and medication-specific to health system-related factors3. Adherence to VTE prophylaxis is not independently attributable to the prescription.
1. Weltgesundheitsorganisation, ed. Adherence to Long-Therm Therapies: Evidence for Action. WHO; 2003.
2. Horwitz RI, Horwitz SM. Adherence to treatment and health outcomes. Arch Intern Med. 1993;153(16):1863-1868.
3. Wilke T, Moock J, Müller S, Pfannkuche M, Kurth A. Nonadherence in outpatient thrombosis prophylaxis with low molecular weight heparins after major orthopaedic surgery. Clin Orthop Relat Res. 2010;468(9):2437-2453. doi:10.1007/s11999-010-1306-8
4. Dietz MJ, Ray JJ, Witten BG, Frye BM, Klein AE, Lindsey BA. Portable compression devices in total joint arthroplasty: poor outpatient compliance. Arthroplast Today. 2020;6(1):118-122. doi:10.1016/j.artd.2019.12.004
5. Carrothers AD, Rodriguez-Elizalde SR, Rogers BA, Razmjou H, Gollish JD, Murnaghan JJ. Patient-reported compliance with thromboprophylaxis using an oral factor Xa inhibitor (rivaroxaban) following total hip and total knee arthroplasty. J Arthroplasty. 2014;29(7):1463-1467. doi:10.1016/j.arth.2013.02.001
6. Lebel B, Malherbe M, Gouzy S, et al. Oral thromboprophylaxis following total hip replacement: the issue of compliance. Orthop Traumatol Surg Res. 2012;98(2):186-192. doi:10.1016/j.otsr.2011.10.010
7. Hood B, Springer B, Odum S, Curtin BM. No difference in patient compliance between full-strength versus low-dose aspirin for VTE prophylaxis following total hip and total knee replacement. Eur J Orthop Surg Traumatol. 2021;31(4):779-783. doi:10.1007/s00590-020-02833-w
8. Moreno JP, Bautista M, Castro J, Bonilla G, Llinás A. Extended thromboprophylaxis for hip or knee arthroplasty. Does the administration route and dosage regimen affect adherence? A cohort study. Int Orthop. 2020;44(2):237-243. doi:10.1007/s00264-019-04454-3
9. Ahmed H, Saddouh EA, Abugrin ME, et al. Association between Patients’ Knowledge and Adherence to Anticoagulants, and Its Effect on Coagulation Control. Pharmacology. 2021;106(5-6):265-274. doi:10.1159/000511754
10. Wong A, Kraus PS, Lau BD, et al. Patient preferences regarding pharmacologic venous thromboembolism prophylaxis. J Hosp Med. 2015;10(2):108-111. doi:10.1002/jhm.2282