Dataset Information

Risk of Hospitalization With Hemorrhage Among Older Adults Taking Clarithromycin vs Azithromycin and Direct Oral Anticoagulants.

ABSTRACT:

Importance

Clarithromycin is a commonly prescribed antibiotic associated with higher levels of direct oral anticoagulants (DOACs) in the blood, with the potential to increase the risk of hemorrhage.

Objective

To assess the 30-day risk of a hospital admission with hemorrhage after coprescription of clarithromycin compared with azithromycin among older adults taking a DOAC.

Design, setting, and participants

This population-based, retrospective cohort study was conducted among adults of advanced age (mean [SD] age, 77.6 [7.2] years) who were newly coprescribed clarithromycin (n = 6592) vs azithromycin (n = 18 351) while taking a DOAC (dabigatran, apixaban, or rivaroxaban) in Ontario, Canada, from June 23, 2009, to December 31, 2016. Cox proportional hazards regression was used to examine the association between hemorrhage and antibiotic use (clarithromycin vs azithromycin). Statistical analysis was performed from December 23, 2019, to March 25, 2020.

Main outcomes and measures

Hospital admission with major hemorrhage (upper or lower gastrointestinal tract or intracranial). Outcomes were assessed within 30 days of a coprescription.

Results

Among the 24 943 patients (12 493 women; mean [SD] age, 77.6 [7.2] years) in the study, rivaroxaban was the most commonly prescribed DOAC (9972 patients [40.0%]), followed by apixaban (7953 [31.9%]) and dabigatran (7018 [28.1%]). Coprescribing clarithromycin vs azithromycin with a DOAC was associated with a higher risk of a hospital admission with major hemorrhage (51 of 6592 patients [0.77%] taking clarithromycin vs 79 of 18 351 patients [0.43%] taking azithromycin; adjusted hazard ratio, 1.71 [95% CI, 1.20-2.45]; absolute risk difference, 0.34%). Results were consistent in multiple additional analyses.

Conclusions and relevance

This study suggests that, among adults of advanced age taking a DOAC, concurrent use of clarithromycin compared with azithromycin was associated with a small but statistically significantly greater 30-day risk of hospital admission with major hemorrhage.

SUBMITTER: Hill K

PROVIDER: S-EPMC7281381 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Although non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used to prevent thromboembolic disease, there are limited data on NOAC-related intracerebral hemorrhage (ICH).To assess the association between preceding oral anticoagulant use (warfarin, NOACs, and no oral anticoagulants [OACs]) and in-hospital mortality among patients with ICH.Retrospective cohort study of 141?311 patients with ICH admitted from October 2013 to December 2016 to 1662 Get With The Guidelines-Stroke hospitals.Anticoagulation therapy before ICH, defined as any use of OACs within 7 days prior to hospital arrival.In-hospital mortality.Among 141?311 patients with ICH (mean [SD] age, 68.3 [15.3] years; 48.1% women), 15?036 (10.6%) were taking warfarin and 4918 (3.5%) were taking NOACs preceding ICH, and 39?585 (28.0%) and 5783 (4.1%) were taking concomitant single and dual antiplatelet agents, respectively. Patients with prior use of warfarin or NOACs were older and had higher prevalence of atrial fibrillation and prior stroke. Acute ICH stroke severity (measured by the National Institutes of Health Stroke Scale) was not significantly different across the 3 groups (median, 9 [interquartile range, 2-21] for warfarin, 8 [2-20] for NOACs, and 8 [2-19] for no OACs). The unadjusted in-hospital mortality rates were 32.6% for warfarin, 26.5% for NOACs, and 22.5% for no OACs. Compared with patients without prior use of OACs, the risk of in-hospital mortality was higher among patients with prior use of warfarin (adjusted risk difference [ARD], 9.0% [97.5% CI, 7.9% to 10.1%]; adjusted odds ratio [AOR], 1.62 [97.5% CI, 1.53 to 1.71]) and higher among patients with prior use of NOACs (ARD, 3.3% [97.5% CI, 1.7% to 4.8%]; AOR, 1.21 [97.5% CI, 1.11-1.32]). Compared with patients with prior use of warfarin, patients with prior use of NOACs had a lower risk of in-hospital mortality (ARD, -5.7% [97.5% CI, -7.3% to -4.2%]; AOR, 0.75 [97.5% CI, 0.69 to 0.81]). The difference in mortality between NOAC-treated patients and warfarin-treated patients was numerically greater among patients with prior use of dual antiplatelet agents (32.7% vs 47.1%; ARD, -15.0% [95.5% CI, -26.3% to -3.8%]; AOR, 0.50 [97.5% CI, 0.29 to 0.86]) than among those taking these agents without prior antiplatelet therapy (26.4% vs 31.7%; ARD, -5.0% [97.5% CI, -6.8% to -3.2%]; AOR, 0.77 [97.5% CI, 0.70 to 0.85]), although the interaction P value (.07) was not statistically significant.Among patients with ICH, prior use of NOACs or warfarin was associated with higher in-hospital mortality compared with no OACs. Prior use of NOACs, compared with prior use of warfarin, was associated with lower risk of in-hospital mortality.