Pharmacodynamic Drug-Drug Interactions and Bleeding Outcomes in Patients with Atrial Fibrillation Using Non-Vitamin K Antagonist Oral Anticoagulants: a Nationwide Cohort Study

被引：4

作者：

Grymonprez, Maxim ^{[1
]}

Capiau, Andreas ^{[1
,2
]}

Steurbaut, Stephane ^{[3
,4
]}

Boussery, Koen ^{[1
]}

Mehuys, Els ^{[1
]}

Somers, Annemie ^{[1
,2
]}

Petrovic, Mirko ^{[5
]}

De Backer, Tine L. ^{[6
]}

Lahousse, Lies ^{[1
,7
]}

机构：

[1] Univ Ghent, Fac Pharmaceut Sci, Dept Bioanal, Pharmaceut Care Unit, Ottergemsesteenweg 460, B-9000 Ghent, Belgium

[2] Ghent Univ Hosp, Pharm Dept, C Heymanslaan 10, B-9000 Ghent, Belgium

[3] Vrije Univ Brussel, Ctr Pharmaceut Res, Res Grp Clin Pharmacol & Clin Pharm, Laarbeeklaan 103, B-1090 Jette, Belgium

[4] UZ Brussel, Dept Hosp Pharm, Laarbeeklaan 101, B-1090 Jette, Belgium

[5] Ghent Univ Hosp, Dept Geriatr, C Heymanslaan 10, B-9000 Ghent, Belgium

[6] Ghent Univ Hosp, Dept Cardiol, C Heymanslaan 10, B-9000 Ghent, Belgium

[7] Erasmus MC, Dept Epidemiol, POB 2040, NL-3000 CA Rotterdam, Netherlands

来源：

CARDIOVASCULAR DRUGS AND THERAPY | 2025年 / 39卷 / 01期

关键词：

Atrial fibrillation; NOAC; Pharmacodynamic drug-drug interaction; Bleeding; Antiplatelet; SSRI; SEROTONIN REUPTAKE INHIBITORS; ANTITHROMBOTIC THERAPY; ANTIPLATELET THERAPY; CONCOMITANT ASPIRIN; WARFARIN; RISK; DABIGATRAN; DISEASE; METAANALYSIS; APIXABAN;

D O I：

10.1007/s10557-023-07521-5

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

PurposePharmacodynamic drug-drug interactions (PD DDIs) may influence the safety of non-vitamin K antagonist oral anticoagulants (NOACs), but the extent to which PD DDIs increase bleeding risks, remains unclear. Therefore, the impact of PD DDIs on bleeding outcomes in NOAC-treated patients with atrial fibrillation (AF) was investigated.MethodsUsing Belgian nationwide data, NOAC-treated AF patients were included between 2013-2019. Concomitant use of PD interacting drugs when initiating NOAC treatment was identified.ResultsAmong 193,072 patients, PD DDIs were identified in 114,122 (59.1%) subjects. After multivariable adjustment, concomitant use of PD interacting drugs was associated with significantly higher risks of major or clinically-relevant non-major bleeding (adjusted hazard ratio (aHR) 1.19, 95% confidence interval (CI) (1.13-1.24)), gastrointestinal (aHR 1.12, 95%CI (1.03-1.22)), urogenital (aHR 1.21, 95%CI (1.09-1.35)) and other bleeding (aHR 1.28, 95%CI (1.20-1.36)), compared to NOAC-treated AF patients without PD interacting drug use. Increased bleeding risks were most pronounced with P2Y12 inhibitors (aHR 1.62, 95%CI (1.48-1.77)) and corticosteroids (aHR 1.53, 95%CI (1.42-1.66)), followed by selective serotonin or serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI, aHR 1.26, 95%CI (1.17-1.35)), low-dose aspirin (aHR 1.14, 95%CI (1.08-1.20)) and non-steroidal anti-inflammatory drugs (NSAID, aHR 1.10, 95%CI (1.01-1.21)). Significantly higher intracranial bleeding risks in NOAC users were observed with SSRI/SNRIs (aHR 1.50, 95%CI (1.25-1.81)) and corticosteroids (aHR 1.49, 95%CI (1.21-1.84)).ConclusionConcomitant use of PD interacting drugs, especially P2Y12 inhibitors and corticosteroids, was associated with higher major, gastrointestinal, urogenital, and other bleeding risks in NOAC-treated AF patients. Remarkably, higher intracranial bleeding risks were observed with SSRI/SNRIs and corticosteroids.

引用

页码：133 / 143

页数：11