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# CYP2D6 phenotype predicts metoprolol heart-rate response but not discontinuation
- URL: https://www.coios.me/cyp2d6-phenotype-predicts-metoprolol-heart-rate-response/
- Published: 2026-10-16T13:18:17.000Z
- Updated: 2026-10-17T08:14:41.000Z
- Description: Reduced CYP2D6 activity lowered attained heart rate and raised bradycardia, but phenotype was not associated with stopping metoprolol.
- Author: Daniel Ryan
- Tags: Data, models and systems, What linked data reveals, Adherence and persistence, United States, #peer-reviewed, #refines, #item, #source-2026-10, #score-78

This retrospective cohort study linked whole-genome sequencing to electronic health records for 44,485 adult metoprolol users in All of Us. Discontinuation meant the last dispensed supply lapsing with no further fill for over 90 days. Discontinuation reached 67.4%; cause-specific hazard ratios versus normal metabolisers were 1.04 (0.99-1.09) poor, 1.01 (0.99-1.03) intermediate. Two alternative supply-gap definitions, with discontinuation rates of 70% and 98%, gave the same null. Poor and intermediate metabolisers had heart rate 1.85 and 0.84 bpm lower, with bradycardia odds ratios 1.19 and 1.16\. Dispensing records miss fills obtained outside the linked system, and requiring two fills excluded single-fill stoppers.

*Why it is interesting: A pharmacogenetic effect clearly present in measured physiology was not seen in rates of stopping the drug. The gap limits what genotype-informed dosing guidance can be expected to achieve.*

Source

[Journal of Clinical Medicine Research, 14 October 2026](https://doi.org/10.14740/jocmr6673?ref=coios.me)

Paper

Cytochrome P450 2D6 Metabolizer Phenotype Is Associated With Metoprolol Pharmacodynamics But Not With Metoprolol Discontinuation: A Retrospective Cohort Study in the All of Us Research Program

Authors

Kachhadia M, Puri P, Buha N, Vadodariya J, Kant S, Giknavorian H et al.

DOI

10.14740/jocmr6673

Full text

[Open copy](https://pmc.ncbi.nlm.nih.gov/articles/PMC13661095/?ref=coios.me) (open-access copy, PubMed Central)

Type

Peer-reviewed article

Design

Retrospective cohort, whole-genome sequencing linked to EHR (All of Us Controlled Tier v9), 44,485 adult metoprolol users; cause-specific Cox regression with death as competing event

Verdict

Refines prior evidence

Driver

[What linked data reveals](https://www.coios.me/d-linked-data/)

Driver

[Adherence and persistence](https://www.coios.me/d-adherence/)

Free full text

[Free to read at the publisher](https://doi.org/10.14740/jocmr6673?ref=coios.me)