Phannita Wattanaruengchai1, Surakit Nathisuwan2, Wipharak Rattanavipanon2, Suvatna Chulavatnatol2, Junporn Kongwatcharapong1, Phatcharin Mitsuntisuk3, Thanaputt Chaiyasothi4, Duangkamon Kritsanapipat5, Arintaya Phrommintikul6, Nathorn Chaiyakunapruk7, Khanchit Likittanasombat8, Gregory Y H Lip9. 1. Pharmacy Department, Siriraj Hospital, Mahidol University, Bangkok, Thailand. 2. Clinical Pharmacy Division, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand. 3. Pharmacy Department, Police General Hospital, Bangkok, Thailand. 4. Department of Clinical Pharmacy, Faculty of Pharmacy, Srinakharinwirot University, Nakhon Nayok, Thailand. 5. Pharmacy Department, Thammasat University Hospital, Bangkok, Thailand. 6. Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. 7. Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, Utah, USA. 8. Division of Cardiology, Department of Internal Medicine, Faculty of Medicine at Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 9. Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, UK.
Abstract
AIMS: This study aimed to evaluate the prescriber compliance to the approved labels of direct oral anticoagulants (DOACs) and impact of appropriateness of dosing on clinical outcomes. METHODS: A retrospective study was conducted using simple-stratified random sampling of adult patients receiving ≥6 months of DOACs for various indications during 2013-2017 in 10 tertiary care hospitals. Patients were classified into 3 dosing groups including approved dose, underdosing and overdosing based on the Thai Food and Drug Administration-approved labels. Cox proportional hazard models were used to evaluate the impact of different dosings on thromboembolic and bleeding events. RESULTS: From 1200 patients included in the data analysis, prescribing of DOACs was consistent with the approved indications in 1130 cases (94.2%) while 70 patients (5.8%) received DOACs despite having contraindications or with off-label usage. Among 1026 cases of dosing evaluation cohort, 688 patients (67.1%) received approved doses. There were 227 (21.9%) and 110 (10.7%) cases of underdosing and overdosing, respectively. Multivariate analysis showed that underdosing was associated with an increased risk of thromboembolism 3.023 (95% confidence interval [CI]: 1.291-7.080; P = .011) while overdosing was associated with an increased risk of bleeding requiring hospitalization (adjusted hazard ratio, 3.045; 95% CI, 1.501-6.178; P = .002) and Bleeding Academic Research Consortium type 2 or more (adjusted hazard ratio, 2.196; 95% CI, 1.083-4.452; P = .029). CONCLUSION: Prescribers' compliance to approved indications were high. However, 1/3 of DOAC prescriptions were inconsistent with approved dosing. Dosing deviation was associated with an increase in adverse clinical outcomes.
AIMS: This study aimed to evaluate the prescriber compliance to the approved labels of direct oral anticoagulants (DOACs) and impact of appropriateness of dosing on clinical outcomes. METHODS: A retrospective study was conducted using simple-stratified random sampling of adult patients receiving ≥6 months of DOACs for various indications during 2013-2017 in 10 tertiary care hospitals. Patients were classified into 3 dosing groups including approved dose, underdosing and overdosing based on the Thai Food and Drug Administration-approved labels. Cox proportional hazard models were used to evaluate the impact of different dosings on thromboembolic and bleeding events. RESULTS: From 1200 patients included in the data analysis, prescribing of DOACs was consistent with the approved indications in 1130 cases (94.2%) while 70 patients (5.8%) received DOACs despite having contraindications or with off-label usage. Among 1026 cases of dosing evaluation cohort, 688 patients (67.1%) received approved doses. There were 227 (21.9%) and 110 (10.7%) cases of underdosing and overdosing, respectively. Multivariate analysis showed that underdosing was associated with an increased risk of thromboembolism 3.023 (95% confidence interval [CI]: 1.291-7.080; P = .011) while overdosing was associated with an increased risk of bleeding requiring hospitalization (adjusted hazard ratio, 3.045; 95% CI, 1.501-6.178; P = .002) and Bleeding Academic Research Consortium type 2 or more (adjusted hazard ratio, 2.196; 95% CI, 1.083-4.452; P = .029). CONCLUSION: Prescribers' compliance to approved indications were high. However, 1/3 of DOAC prescriptions were inconsistent with approved dosing. Dosing deviation was associated with an increase in adverse clinical outcomes.
Authors: Pierpaolo Di Micco; Vladimir Rosa Salazar; Carmen Fernandez Capitan; Francesco Dentali; Covadonga Gomez Cuervo; Jose Luis Fernandez Torres; Jose Antonio Porras; Angeles Fidalgo; Elvira Grandone; Manuel Lopez Meseguer; Manuel Monreal Journal: Life (Basel) Date: 2022-07-27