Structured pharmaceutical interviews enhance knowledge and medication adherence in DOAC therapy: Insights from the EDUC-AOD study.

Background Direct oral anticoagulants (DOACs) are first-line therapies for atrial fibrillation and venous thromboembolism. Structured pharmaceutical interviews aim to improve patient knowledge of DOAC therapy, thereby enhancing medication adherence and reducing both disease-related and drug-related clinical complications. Purpose The EDUC-AOD study was conducted to assess the impact of structured pharmaceutical interviews on patient knowledge, medication adherence, and clinical complications. Methods Patients newly prescribed DOACs were enrolled from two centers, with only one center delivering structured pharmaceutical interviews. The primary objective was to assess the effect of structured pharmaceutical interviews on both knowledge and medication adherence scores at 3 months (M3), using standardized questionnaires. Secondary objectives included evaluating the impact of structured pharmaceutical interviews on clinical complications, as well as knowledge and medication adherence at 6 months (M6). Multivariate logistic regression analysis was used to identify predictors of improved knowledge and medication adherence. Results From January 2021 to June 2023, 145 patients were enrolled: 68 in the intervention group and 77 in the control group. Among these, 127 patients completed the follow-up and were included in the analysis. At M3, the intervention group demonstrated significantly higher rates of satisfactory knowledge (74% vs. 12%, p<0.001) and good medication adherence (86% vs. 64%, p=0.008). At M6, the intervention group experienced significantly fewer hemorrhagic complications (0 vs. 9, p=0.010). Structured pharmaceutical interviews and treatment indication were identified as significant predictors of satisfactory knowledge (OR = 31, p<0.001; OR = 5, p=0.003, respectively). Conclusion Structured pharmaceutical interviews substantially enhance patients’ knowledge and medication adherence to DOAC therapy and reduce clinical complications. Integrating structured pharmaceutical interviews into routine care may optimize anticoagulant management. Further randomized trials are needed to confirm these findings.Baseline patient characteristicsKnowledge & Adherence assesment

Direct Oral Anticoagulants for Prevention of Recurrent Thrombosis in Myeloproliferative Neoplasms

Background: Direct oral anticoagulant (DOAC) therapy may be a safe and effective oral alternative to low-molecular-weight heparin (LMWH) or warfarin therapy for treatment for cancer-associated venous thromboembolism. Whether differences exist in adherence and persistence to these medications in this clinical setting is unknown. Methods: We identified all Kaiser Permanente members in the Colorado and Northern California regions who experienced a hospitalization for a cancer-associated thromboembolism between 2014-2017 (index event). The primary exposure was the initial anticoagulant regimen used which we defined using outpatient pharmacy dispense records in the 30-days after hospital discharge: 1) DOAC ± an injectable, 2) low-molecular weight heparin monotherapy, or 3) warfarin ± an injectable (index regimen). The primary outcome was medication adherence (i.e., the proportion of days covered) and medication persistence and reasons for non-persistence (i.e., the time to medication discontinuation, regimen change, or death) over the next 6-months. We used Kaiser Permanente’s comprehensive electronic health records to define patient’s demographic and cancer characteristics, comorbidities (inpatient and outpatient ICD-9-CM diagnoses), and other medication use. Multivariable log-binomial models were used to calculate adjusted risk ratios and 95% confidence intervals for adherence >80% and persistence >6 months associated with DOAC use. Results: Of the 2,843 patients included, the mean age was 66±13 and 1,523 (54%) were female. Patients receiving DOAC therapy were more likely to be older and have less advanced stages of cancer. In the 6-months post-index, DOAC therapy was associated with higher adherence than LMWH monotherapy and higher persistence than warfarin therapy (Table 1). When non-persistence was observed during the 6 months, the distribution of reasons for non-persistence varied significantly by index regimen with patients receiving DOAC therapy significantly more likely to stop filling the medication as opposed to death or switching regimens. Conclusion: In this large community-treated population, initial anticoagulation therapy with a DOAC was associated with improved adherence and persistence rates compared to traditional therapies.

IntroductionPostmarketing pharmacovigilance reports have raised concerns about non-bleeding adverse events associated with direct oral anticoagulants (DOACs), but only limited results are available from large claims databases.ObjectiveThe aim of this study was to assess the potential association between DOAC initiation and the onset of four types of non-bleeding adverse events by sequence symmetry analysis (SSA).MethodsSSA was performed using nationwide data from the French National Healthcare databases (Régime Général, 50 million beneficiaries) to assess a cohort of 386,081 DOAC new users for the first occurrence of four types of non-bleeding outcomes: renal, hepatic, skin outcomes identified by using hospitalization discharge diagnoses, and gastrointestinal outcomes by using medication reimbursement. Asymmetry in the distribution of each investigated outcome occurring before and after initiation of DOAC therapy was used to test the association between DOAC therapy and these outcomes. SSA inherently controls for time-constant confounders, and adjusted sequence ratios were computed after correcting for temporal trends. Negative (glaucoma) and positive (bleeding, depressive disorders) control outcomes were used and analyses were replicated on a cohort of 310,195 patients initiating a vitamin K antagonist (VKA).ResultsThis study demonstrated the expected positive association between either DOAC or VKA therapy and hospitalised bleeding and initiation of antidepressant therapy, while no association was observed between either DOAC or VKA therapy and initiation of antiglaucoma medications. For DOAC therapy, signals were the associations with hepatic outcomes, including acute liver injury [for the 3-month time window, aSR3 = 2.71, 95% confidence interval (CI) 1.79–4.52]; gastrointestinal outcomes, including initiation of drugs for constipation and antiemetic drugs (aSR3 = 1.31, 95% CI 1.27–1.36; and 1.17, 95% CI 1.12–1.22, respectively); and kidney diseases (aSR3 = 1.33, 95% CI 1.29–1.37).ConclusionResults of this nationwide study suggest that DOACs are associated with rare but severe liver injury and more frequent gastrointestinal disorders. A low risk of kidney injury with DOAC therapy can also not be excluded.Electronic supplementary materialThe online version of this article (10.1007/s40264-018-0668-9) contains supplementary material, which is available to authorized users.

The efficacy and bleeding complications of direct oral anticoagulant (DOAC) therapy for cancer-associated venous thromboembolism (VTE) in routine clinical practice remain unclear. Moreover, data on long-term outcomes in patients with cancer-associated VTE who received DOAC therapy are limited.Methods and Results:This retrospective study enrolled 1,096 consecutive patients with acute VTE who received warfarin or DOAC therapy between April 2014 and May 2017. The mean follow-up period was 665±490 days. The number of cancer-associated VTE patients who received DOAC therapy was 334. Patients who could not be followed up and those prescribed off-label under-dose DOAC were excluded. Finally, 303 patients with cancer-associated VTE were evaluated. The number of cases of major bleeding and VTE recurrence was 54 (17.8%) and 26 (8.6%), respectively. In the multivariate analysis, the factors correlated with major bleeding were high cancer stage, high performance status, liver dysfunction, diabetes mellitus, and stomach cancer; those correlated with recurrent VTE were initial diagnosis of pulmonary embolism, uterine cancer, and previous cerebral infarction. Major bleeding was an independent risk factor of all-cause death. In the Kaplan-Meier analysis, those who received prolonged DOAC therapy had lower composite major bleeding and recurrent VTE risks than those who did not. In DOAC therapy for cancer-associated VTE, major bleeding prevention is important because it is an independent risk factor of death.

Extended DOAC therapy in patients with VTE and potential risk of recurrence: A systematic review and meta‐analysis

Adherence to and persistence with direct oral anticoagulant therapy among patients with new onset venous thromboembolism receiving extended anticoagulant therapy and followed by a centralized anticoagulation service

To evaluate the efficacy and safety of direct oral anticoagulant (DOAC) therapy in hospitalized patients with suspected heparin-induced thrombocytopenia (HIT). Retrospective cohort study of adult patients prescribed apixaban, dabigatran, or rivaroxaban for the treatment of acute HIT from January 1, 2013 to January 1, 2017. Eligibility requirements included an intermediate or high pretest probability for HIT (4T score≥4) and a positive IgG-specific anti-PF4/heparin complex assay. The primary outcome measure was the composite of newly diagnosed venous or arterial thromboembolism, gangrene, or amputation due to critical limb ischemia during hospitalization. A total of 12 patients were included for analysis, five of which experienced HIT-related thrombosis prior to initiation of DOAC therapy. Seven patients received parenteral therapy with argatroban prior to initiation of DOAC treatment. Nine patients were treated with apixaban while three received rivaroxaban for an average of 9.33days while hospitalized. Zero patients experienced the primary outcome of HIT-related thrombosis, and no patients experienced major bleeding post DOAC initiation. All patients achieved platelet recovery while receiving DOAC therapy. In this small retrospective study of adult patients treated for acute HIT, treatment with DOAC therapy was not associated with in-hospital thrombotic or hemorrhagic events.

243 Background: National Comprehensive Cancer Network recommends direct oral anticoagulants (DOACs) as preferred agents for treatment of cancer associated VTE in patients without gastric or gastroesophageal lesions. Currently at Massachusetts General hospital (MGH), DOACs are used in treatment of cancer associated VTE. This study was performed to evaluate the safety and efficacy of DOACs for treatment of VTE in patients with metastatic lung cancer. Methods: Retrospective chart review of patients at MGH with diagnosis of metastatic lung cancer who were prescribed edoxaban, rivaroxaban, or apixaban for treatment of VTE between January 2018 and January 2021 was performed. Patients were identified using electronic medical record reports. Data was collected on age, anticoagulation regimen, intent of anticoagulation therapy, presence of brain metastasis, renal function, liver function and platelet counts. The primary outcome was to assess the incidence of treatment failure, defined as VTE recurrence or major bleeding leading to a change in anticoagulation therapy. Results: 152 patients were evaluated, of which 57 received apixaban, 44 rivaroxaban, and 7 edoxaban. Most (n = 93) patients received enoxaparin for 14-90 days prior to transitioning to DOACs. Median age and creatinine clearance were 69 years and 63 mL/min, respectively. All patients had platelet count ≥ 50K/uL. Brain metastasis was present in n = 39 patients. Pulmonary embolism (PE)(n = 98), deep vein thrombosis (DVT) (n = 52), or both (n = 2) were the indication for DOAC therapy. Bleeding occurred in 14 patients including gastrointestinal bleeding (n = 5), hematuria (n = 4), epistaxis (n = 1), and hemoptysis (n = 4). Among patients with bleeding events, 7 received rivaroxaban and 7 received apixaban. Major recurrent VTE while on DOACs occurred in 5 of patients, including DVT (n = 2) and PE (n = 3). Patients with recurrent VTE received rivaroxaban (n = 7), apixaban (n = 3) and edoxaban (n = 1). All patient whom experienced bleeding and VTE were ≥ 60 years old. Brain metastasis was present in n = 2 of patients with bleeding events and n = 2 patients with recurrent VTE. Majority of patients (n = 93) received enoxaparin for 14-90 days prior to transitioning to DOACs. The median interval between initiation of DOACs and bleeding was 60 days (range 30-365) and recurrent VTE event was 90 days (range 60‐365). Conclusions: The results of this study suggest that outcomes of DOAC use for the treatment of cancer-associated VTE in patients with metastatic lung cancer are comparable to the results of large randomized controlled trials. DOAC therapy is a safe and effective anticoagulation option for lung cancer patients with cancer-associated thromboembolism.

Safety and Efficacy of Direct Oral Anticoagulants in Comparison to Low Molecular Weight Heparin in Hematological Malignancies

Treatment for hepatitis C virus (HCV) with direct-acting antivirals (DAA) is advantageous over previous treatment options due to high efficacy, short treatment duration, and relatively few drug interactions. Similarly, direct oral anticoagulants (DOAC) are generally preferred over warfarin for the management of thrombosis and atrial fibrillation due to a favourable safety profile. Direct-acting antivirals inhibit DOAC transport through P-glycoprotein inhibition leading to a theoretical increase in bleeding risk. We evaluated the incidence of bleeding in patients who received concurrent DAA and DOAC therapy and stratified the analysis based on the patient's cirrhosis status. We conducted a multicenter, retrospective cohort study to evaluate bleeding in patients with HCV and cirrhosis compared to patients with HCV without cirrhosis. Patients receiving at least 1 month of overlapping DAA and DOAC therapy between May 2017 and August 2020 at 11 medical centers in the United Kingdom and three medical centers in the United States were included. Charts were manually reviewed to identify baseline characteristics as well as thromboembolic or bleeding events. Bleeding events were categorized as major bleeding (MB) and clinically relevant non-major bleeding (CRNMB). Of 204 total patients, 36 patients (18%) had cirrhosis and 168 patients (82%) did not have cirrhosis. The majority of patients were male (79%) and Caucasian (75%). Sofosbuvir/velpatasvir (32%) and rivaroxaban (57%) were the most commonly prescribed DAA and DOAC, respectively. Leading indications for anticoagulation included thrombosis (75%) and atrial fibrillation (21%). There were three MB events (1.5%) all of which occurred in patients with additional risk factors (age over 65 and on antiplatelet therapy) and no CRNMB occurred while on DOAC and DAA therapy. Of the three MB, one occurred in a patient with cirrhosis and two in patients without cirrhosis, RR 1.23 (0.56-2.76). In conclusion, in this multicenter cohort study of concurrent DAA and DOAC use, MB was uncommon and there was no CRNMB. There was no significant difference in bleeding events among patients with cirrhosis compared to those without cirrhosis. These findings support the use of DAA among patients requiring DOAC.

The Kansas City Bleeding Index: A Clinical Assessment Tool to Predict Risk of Major Bleeding Events on Doac Therapy

Effectiveness and Safety of the Direct Oral Anticoagulants in Low-Risk Antiphospholipid Syndrome: A Case Series

Context:Medication and low salt diet adherence play as an essential factor in blood pressure target achievement. Community health worker empowerment was reported to be a highly effective social intervention to medication and low salt diet adherence.Aims:This study aimed to investigate the effect of structured health education regarding hypertension on community health workers on medication and low salt diet adherence among hypertensive patients in Malang.Subjects and Methods:A quasi-experimental study was conducted in health workers and their hypertensive patients who join in the Integrated Health Service Post for the Elderly (IHSP-Elderly) program in Malang. Medication adherence was measured by the medication adherence questionnaire and low salt diet adherence was measured by dietary salt restriction questionnaire. The data were analyzed by Chi-square analysis for categorical data and independent t-test for numerical data.Results:This study showed that hypertensive patients in the intervention group had better knowledge regarding hypertension compared to those of the control group (P < 0.05). The patients' satisfaction in intervention group improved significantly after health education (P < 0.01). The proportion of patients with good medication adherence improved significantly (P < 0.01) from 20% to 70% after health education in intervention group. Moreover, the proportion of patients with good low salt diet compliance improved significantly (P < 0.01) from 39% to 85%. Conversely, the proportion of good medication and low salt diet adherence in control group relatively similar between pre- and post-test.Conclusions:This study showed that health education on community health workers improved hypertensive patients' medication and low salt diet adherence.

ABSTRACTObjectives: To investigate whether direct oral anticoagulant (DOAC) therapy at acute hospitals is continued after transfer to subacute or chronic hospitals and geriatric health services facilities in Japan.Methods: Acute hospitals routinely transfer patients to nearby subacute or chronic hospitals and geriatric health services facilities after acute stroke treatment. To elucidate the status of antithrombotic therapy, particularly DOAC therapy, we conducted a questionnaire survey of chief physicians at 33 subacute or chronic hospitals and geriatric health services facilities in the vicinity of Kawasaki City.Results: Responses were received from 23 hospitals and geriatric health services facilities (5 convalescent and rehabilitation hospitals, 5 chronic hospitals, 13 geriatric health services facilities). The number of convalescent hospitals responding, ‘no problem with DOAC administration’ before transfer to subacute or chronic hospitals and geriatric health services facilities increased from 4 (80%) at the introduction of DOACs to 5 (100%) presently. The number of chronic hospitals and geriatric health services facilities also increased from 1 (20%) to 3 (60%) and 4 (30.8%) to 5 (38.5%), respectively, albeit not significantly. The number of convalescent hospitals, chronic hospitals, and geriatric health services facilities requesting pre-transfer change of oral anticoagulants decreased from 20% to 0%, 60% to 40%, and 69.2% to 61.5%, respectively. All convalescent hospitals continued DOAC therapy after transfer. However, only 40.0% of chronic hospitals and 46.2% of geriatric health services facilities used DOACs in the present period. Warfarin was used instead at 3 (60%) chronic hospitals and 7 (53.8%) geriatric health services facilities and antiplatelet drugs were used at 1 hospital/facility each (20% and 7.7%, respectively). Nine (39.1%) hospitals and facilities cited high DOAC costs for the switch.Conclusions: Convalescent hospitals have incorporated DOAC use and readily accept patients receiving DOACs at transferring hospitals. Conversely, many chronic hospitals and geriatric health services facilities eventually switch from DOACs to warfarin or antiplatelet drugs due to cost. Efforts to resolve these barriers to continued administration of DOACs between acute hospitals and subacute or chronic hospitals and geriatric health services facilities in Japan are needed as soon as possible.