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Drug Utilization Pattern of Oral Anticoagulants in Patients with Atrial Fibrillation: A Nationwide Population-Based Study in Korea

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Abstract

Introduction

Treatment persistence for anticoagulant therapy is important in preventing thromboembolism in nonvalvular atrial fibrillation (NVAF) patients. Understanding drug utilization pattern and treatment changes in oral anticoagulant (OAC) users may facilite better NVAF management. Thus, our study aimed to examine OAC treatment patterns preceding events leading to switch or discontinuation and medication adherence in Korean NVAF patients.

Methods

We conducted a drug utilization study on all Korean patients with atrial fibrillation (AF) newly prescribed OACs between July 2015 and November 2016 using the national claims data. We assessed treatment changes such as switching and discontinuation from index OAC and relevant events preceding the change and examined patient characteristics as predictors of changes that occurred among OAC users. Medication adherence was compared among OAC users by calculating the medication possession ratio (MPR).

Results

A total of 48,389 NVAF patients were identified who initiated OACs within the study period. Most initiated nonvitamin K antagonist oral anticoagulants (NOACs) (22% apixaban, 24% dabigatran, 37% rivaroxaban), and 18% initiated warfarin. The frequency of switch to another OAC was 8.8% for apixaban, 16.1% for dabigatran, 6.6% for rivaroxaban, and 19.1% for warfarin. The frequency of discontinuation was lower for apixaban (22.9%), dabigatran (26.3%), and rivaroxaban (25.7%) than warfarin (31.6%). Compared to warfarin, NOAC users were less likely to switch treatment. Thromboembolic event was the most common clinical event preceding switch from warfarin to NOAC and from NOAC to warfarin. Discontinuation of OAC was often preceded by a bleeding event. Patients who initiated apixaban showed significantly higher mean MPR compared to those on dabigatran and warfarin.

Conclusion

In real-world practice in Korea, we have observed treatment change to be common in OAC users. Our results indicate better medication adherence with NOACs than with warfarin. (ClinicalTrials.gov registration number NCT03572972).

Plain language summary

Anticoagulants are drugs that thin blood with the purpose of preventing thromboembolic disease (e.g., stroke), which is a disease occurring when a blood clot forms or blocks vessel. Maintaining treatment for anticoagulation is important to prevent stroke in atrial fibrillation (AF) patients. To understand current drug usage pattern and treatment changes related to oral anticoagulants (OAC) we examined OAC treatment patterns and preceding events that led to drug switch or stop and medication maintenance by Korean AF patients.

The study was conducted by utilizing the Korean national claims data from July 2015 to November 2016. All AF patients who newly started taking OAC were included in the analysis. In total, 48,389 patients were identified with most (83%) taking nonvitamin K antagonist oral anticoagulants (NOAC), which are newer generation blood thinners, including apixaban, dabigatran, and rivaroxaban, and 18% taking warfarin, the conventional blood thinner. Compared to warfarin, NOAC users were less likely to switch to other treatment. NOAC users discontinued the treatment less frequently than warfarin users. Thromboembolic events commonly preceded switch between OACs. Patients who stopped taking OACs were often confronted with a bleeding event before stopping treatment. Apixaban takers showed higher treatment persistence compared to dabigatran or warfarin users. In this study, we determined that treatment change is common in OAC-using patients. The results suggest that NOAC users may better adhere to treatment than warfarin users.

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Acknowledgements

Funding

This study was sponsored by Pfizer and Bristol-Myers Squibb; the Journal’s Rapid Service Fee was funded by Pfizer.

Medical Writing, Editorial, and Other Assistance

Editorial support on English language was provided by Enago (www.enago.co.kr) and was funded by Pfizer and Bristol Myers Squibb.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Author Contributions

Conceptualization: Sola Han, Yoo-Jung Park, and Hae Sun Suh; Methodology: Sola Han and Hae Sun Suh; Investigation: Myong-Yong Lee, Sola Han, Oh Young Bang, Young-Keun On, Sung-Won Jang, Seongwook Han, Hae Sun Suh and Young-Hoon Kim; Data curation and Formal analysis: Sola Han and Hae Sun Suh; Writing—original draft preparation: Myong-Yong Lee, Sola Han, Jaeyun Ryu, Yoo-Jung Park and Hae Sun Suh; Writing—review and editing: All authors; Project administration: Jaeyun Ryu, Yoo-Jung Park and Seongsik Kang; Supervision: Yoo-Jung Park, Seongsik Kang, Hae Sun Suh and Young-Hoon Kim.

Prior Presentation

The abstract of this study was presented at American Heart Association 2018 Congress in Chicago, IL, USA, in November 2018.

Disclosures

Authors Jaeyun Ryu, Yoo-Jung Park, and Seongsik Kang are full-time employees and stockholders of Pfizer Inc. Authors Myung-Yong Lee, Sola Han, Oh Young Bang, Young Keun On, Sung-Won Jang, Seongwook Han, Hae Sun Suh, and Young-Hoon Kim are paid consultants for Pfizer Korea Ltd.

Compliance with Ethics Guidelines

Ethical clearance for the study was exempted by the institutional review board at Pusan National University (PNU IRB/2016_137_HR).

Data Availability

The study data were extracted and analyzed from the Korean Health Insurance Review & Assessment Service (HIRA) claims database, and additional data may be obtained from third party (with appropriate authorization approval) but are not publicly available.

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Author notes

  1. M. Lee and Sola Han are co-first authors.

  2. Hae Sun Suh and Y-H. Kim are co-corresponding authors.

Authors and Affiliations

  1. Division of Cardiology, Department of Internal Medicine, Dankook University, Chung Nam, South Korea

    Myung-Yong Lee

  2. Pharmaceutical Economics, Big Data Analysis & Policy, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, South Korea

    Sola Han & Hae Sun Suh

  3. Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Oh Young Bang

  4. Department of Cardiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Young Keun On

  5. Division of Cardiology, Department of Internal Medicine, Catholic University of Korea, Seoul, South Korea

    Sung-Won Jang

  6. Division of Cardiology, Department of Internal Medicine, Dongsan Hospital, Keimyung University School of Medicine, Daegu, South Korea

    Seongwook Han

  7. Pfizer Korea Ltd, Seoul, South Korea

    Jaeyun Ryu, Yoo-Jung Park & Seongsik Kang

  8. Division of Cardiology, Department of Internal Medicine, College of Medicine, Korea University Medical Center, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul, South Korea

    Young-Hoon Kim

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Correspondence to Hae Sun Suh or Young-Hoon Kim.

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Lee, MY., Han, S., Bang, O.Y. et al. Drug Utilization Pattern of Oral Anticoagulants in Patients with Atrial Fibrillation: A Nationwide Population-Based Study in Korea. Adv Ther 39, 3112–3130 (2022). https://doi.org/10.1007/s12325-022-02151-z

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