No Study from Annals of Internal Medicine Addressed This Question
The evidence provided does not include any study from Annals of Internal Medicine that directly addresses the risks and management of bleeding when using apixaban and diltiazem concomitantly.
Key Evidence Sources Identified
The most relevant and high-quality evidence addressing this drug interaction comes from:
Primary Research Evidence
- JAMA 2024: A large Medicare study (n=204,155) found diltiazem increased serious bleeding risk with apixaban/rivaroxaban compared to metoprolol, particularly at doses >120 mg/day 1
- Journal of the American Heart Association 2022: Demonstrated increased bleeding risk with diltiazem-DOAC combinations in atrial fibrillation patients 2
- JAMA Network Open 2020: Found no increased bleeding with apixaban-diltiazem combination, but significant risk with dabigatran 3
Guideline Evidence
- Circulation: Arrhythmia and Electrophysiology 2022: States diltiazem did not significantly increase plasma concentrations of apixaban and may be a more suitable combination compared to verapamil 4
- European Respiratory Review 2022: Notes that diltiazem (moderate CYP3A4 inhibitor) increased apixaban exposure by 40%, which is considered clinically manageable 4
The Discrepancy in Evidence
There is contradictory evidence regarding apixaban-diltiazem interactions:
- Older guideline statements suggest the combination is relatively safe 4
- The most recent and highest-quality study (JAMA 2024) demonstrates increased bleeding risk, especially with diltiazem doses exceeding 120 mg/day 1
The 2024 JAMA study should take precedence as it represents the largest real-world cohort with the most rigorous methodology and most recent data 1.