Unintentional guideline deviations in hospitalized patients with two or more antithrombotic agents: an intervention study.

PURPOSE: Treatment schedules for antithrombotic therapy are complex, and there is a risk of inappropriate prescribing or continuation of antithrombotic therapy beyond the intended period of time. The primary aim of this study was to determine the frequency of unintentional guideline deviations in hospitalized patients. Secondary aims were to determine whether the frequency of unintentional guideline deviations decreased after intervention by a pharmacist, to determine the acceptance rate of the interventions and to determine the type of interventions. METHODS: We performed a non-controlled prospective intervention study in three teaching hospitals in the Netherlands. We examined whether hospitalized patients who used the combination of an anticoagulant plus at least one other antithrombotic agent had an unintentional guideline deviation. In these cases, the hospital pharmacist contacted the physician to assess whether this deviation was intentional. If the deviation was unintentional, a recommendation was provided how to adjust the antithrombotic regimen according to guideline recommendations. RESULTS: Of the 988 included patients, 407 patients had an unintentional guideline deviation (41.2%). After intervention, this was reduced to 22 patients (2.2%) (p < 0.001). The acceptance rate of the interventions was 96.6%. The most frequently performed interventions were discontinuation of an low molecular weight heparin in combination with a direct oral anticoagulant and discontinuation of an antiplatelet agent when there was no indication for the combination of an antiplatelet agent and an anticoagulant. CONCLUSION: A significant number of hospitalized patients who used an anticoagulant plus one other antithrombotic agent had an unintentional guideline deviation. Intervention by a pharmacist decreased unintentional guideline deviations.

Guidelines for mono, double and triple antithrombotic therapy.

Guidelines for antithrombotic therapy are complex, especially if a patient has several indications that require antithrombotic therapy. In general, no patient should receive lifelong double or triple antithrombotic therapy. In this overview, we outline the most common indications for mono, double and triple antithrombotic therapy; the preferred antithrombotic therapy and the recommended duration of therapy. Both antiplatelet therapy and therapeutic anticoagulation therapy with vitamin K antagonists or direct oral anticoagulants were included. European guidelines were used or, if no European guidelines were available, the Dutch guidelines were used.

Drug-drug interactions with metronidazole and itraconazole in patients using acenocoumarol.

PURPOSE: Various population-based cohort studies have shown that antimicrobial agents increase the risk of overanticoagulation in patients using coumarins. In this study, we assessed this association in hospitalized patients. METHODS: We included all patients hospitalized in the Spaarne Gasthuis (Haarlem/Hoofddorp, the Netherlands), who started using an antimicrobial agent during acenocoumarol treatment or vice versa between 1 January 2015 and 1 July 2019. Patients were followed from start of concomitant therapy until 48 h after termination of the concomitant therapy or discharge, whichever came first. We analyzed the association between the antimicrobial agents and the risk of overanticoagulation, defined as an interpolated INR above 6, using Cox regression analysis. We corrected for multiple testing with the Bonferroni correction. Patients who started using acenocoumarol and amoxicillin/clavulanic acid were used as reference group. RESULTS: In the study population, sixteen antimicrobial agents were started frequently concomitantly with acenocoumarol treatment. We included 2157 interaction episodes in 1172 patients. Patients who started using the combination of co-trimoxazole (HR 3.76; 95% CI 1.47-9.62; p = 0.006), metronidazole (HR 2.55; 95% CI 1.37-4.76; p = 0.003), or itraconazole (HR 4.11; 95% CI 1.79-9.45; p = 0.001) concomitantly with acenocoumarol treatment had an increased risk of overanticoagulation compared with patients using acenocoumarol and amoxicillin/clavulanic acid concomitantly. The associations for metronidazole (p = 0.045) and itraconazole (p = 0.015) remained statistically significant after correction for multiple testing. CONCLUSION: Co-trimoxazole, metronidazole, and itraconazole increase the risk of overanticoagulation in patients using acenocoumarol. These combinations should be avoided if possible or otherwise acenocoumarol doses should be reduced and INR measured more frequently.

Antithrombotic Questionnaire Tool for Evaluation of Combined Antithrombotic Therapy in Community Pharmacies.

OBJECTIVE: The objective of this paper is to assess the diagnostic value of an antithrombotic questionnaire tool compared with the hospital's medical record information tool. The hypothesis of this study was that the antithrombotic questionnaire tool could identify patients with potentially incorrect antithrombotic therapy. METHODS: This cross-sectional study was conducted in eight community pharmacies in the Netherlands. A standardized questionnaire was developed as antithrombotic questionnaire tool. The pharmacist assessed whether the antithrombotic therapy was correct or potentially incorrect based on answers given by patients and based on the medical record. The primary outcome of the study was the sensitivity and specificity of the antithrombotic questionnaire tool to identify patients with potentially incorrect antithrombotic therapy. RESULTS: For 95 patients, the pharmacist assessed that in 81 (85%) the antithrombotic therapy was correct and in 14 (15%) potentially incorrect. Based on the medical record, 86 patients (91%) were assessed as correct and 9 (9%) as potentially incorrect. The sensitivity of the tool was 100% and the specificity 94%. CONCLUSIONS: This study demonstrated that the antithrombotic questionnaire tool is a suitable tool to assess whether the patient's antithrombotic therapy is potentially incorrect. It can be applied to identify patients with potentially incorrect antithrombotic therapy.

Smaller nadroparin dose reductions required for patients with renal impairment: A multicenter cohort study.

BACKGROUND: Guidelines advise 50 % and 25 % dose reduction of the therapeutic nadroparin dose (86 IU/kg) in patients with eGFR 15-29 and 30-60 ml/min respectively. For monitoring, peak anti-Xa levels are suggested. Data lack whether this results in therapeutic anti-Xa levels or in anti-Xa levels that are comparable to those of patients without renal impairment. AIMS: To determine dose ranges in patients with renal impairment that result in therapeutic anti-Xa levels and to determine the percentage of the 86 IU/kg dose that results in anti-Xa levels normally occurring in patients without renal impairment. METHODS: A retrospective cohort study was conducted in five hospitals. Patients ≥18 years of age, with an eGFR ≥ 15 ml/min were included. The first correctly sampled peak (i.e. 3-5 h after ≥ third administration, regardless of dose per patient) was included. Simulated prediction models were developed using multiple linear regression. RESULTS: 770 patients were included. eGFR and hospital affected the association between dose and anti-Xa level. The doses for peak anti-Xa levels of 0.75 IU/ml differed substantially between hospitals and ranged from 55 to 91, 65-359 and 68-168 IU/kg in eGFR 15-29, 30-60 and > 60 ml/min/1.73m2, respectively. In eGFR 15-29 and 30-60 ml/min/1.73m2, doses of 75 % and 91 % of 86 IU/kg respectively, were needed for anti-Xa levels normally occurring in patients with eGFR > 60 ml/min. CONCLUSION: We advise against anti-Xa based dose-adjustments as long as anti-Xa assays between laboratories are not harmonized and an anti-Xa target range is not validated. A better approach might be to target levels similar to eGFR > 60 ml/min/1.73m2, which are achieved by smaller dose reductions.

Implementation of a Patient Questionnaire in Community Pharmacies to Improve Care for Patients Using Combined Antithrombotic Therapy: A Qualitative Study.

For several indications or combinations of indications the use of more than one antithrombotic agent is required. The duration of combined antithrombotic therapy depends on indication and patient characteristics. This study investigated the use of an antithrombotic questionnaire tool that had been developed for pharmacists to detect patients with possible incorrect combined antithrombotic therapy. The objective of this study was to identify potential barriers and facilitators that could influence the implementation of the developed antithrombotic questionnaire tool in daily community pharmacy practice. A qualitative study was conducted at 10 Dutch community pharmacies in which the antithrombotic questionnaire tool had been used with 82 patients. Semi-structured interviews were conducted with pharmacy staff who used the antithrombotic questionnaire tool. The interview questions to identify barriers and facilitators were based on the Consolidated Framework for Implementation Research. The interview data were analysed using a deductive thematic analysis. Ten staff members from nine different pharmacies were interviewed. Facilitators for implementation were that the questionnaire was easily adaptable and easy to use, as well as the relative short duration to administer the questionnaire. A possible barrier for using the questionnaire was a lower priority for using the questionnaire at moments when the workload was high. The pharmacists estimated that the questionnaire could be used for 70-80% of the patient population and they thought that it was a useful addition to regular medication surveillance. The antithrombotic questionnaire tool can be easily implemented in pharmacy practice. To implement the tool, the focus should be on integrating its use into daily activities. Pharmacists can use this tool in addition to regular medication surveillance to improve medication safety in patients who use combined antithrombotic therapy.