Evidence mapPaperPMID 42449494Full record

ArticlePharmacoepidemiology and drug safety2026

Long-Term Cardiovascular Risks of Anticholinergic Versus Non-Anticholinergic Antidepressants: A Target Trial Emulation With Negative Control Correction.

Yang Xu, Hong Xu, Jinxin Guo, Qoua Liang Her, Ruyu Li, Yongjie Lai, Yue Zhang, Edwin C K Tan, Siyan Zhan

Abstract readComparative Study
In one paragraph

Article in Pharmacoepidemiology and drug safety, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Yang XuDepartment of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.ORCID https://orcid.org/0000-0002-1074-608X
Hong XuDepartment of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.ORCID https://orcid.org/0000-0002-7266-3431
Jinxin GuoKey Laboratory of Epidemiology of Major Diseases, Ministry of Education/Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
Qoua Liang HerDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Ruyu LiDepartment of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Yongjie LaiDepartment of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Yue ZhangDepartment of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Edwin C K TanSchool of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Siyan ZhanKey Laboratory of Epidemiology of Major Diseases, Ministry of Education/Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.

Funding

American Diabetes Association 1-25-PDF-96Gates Foundation INV-035024National Natural Science Foundation of China 72361127500National Natural Science Foundation of China 82304245National Natural Science Foundation of China 82330107
6 · The paper itself

Abstract

purposeAntidepressants remain widely prescribed worldwide, and the potential cardiovascular risks associated with their anticholinergic properties are poorly understood.

methodsWe employed an active-comparator new-user design to emulate a target trial spanning 2006-2021 in UK Biobank. Participants aged ≥ 40 years with linked primary care records who newly initiated an anticholinergic vs. a non-anticholinergic antidepressant were included. The primary outcome was hospitalization or death from cardiovascular events. To adjust for measured and unmeasured confounding, we applied propensity score matching (PSM) with proximal causal inference (PCI) and negative control outcome calibration (NCOC) to estimate the intention-to-treat hazard difference (HD). Subgroup analyses were conducted by age, sex, socioeconomic status, lifestyle factors, apolipoprotein E genotype, and major comorbidities. Sensitivity analyses included data-driven negative control selection, alternative anticholinergic burden scale, comparisons across different anticholinergic burden levels, complete-case analysis, a 6-month induction period, and a 2-year washout period.

resultsThe study included 24 547 anticholinergic antidepressant users and 20 519 non-anticholinergic users. Measured covariates were balanced among 32 588 PS-matched participants with a median follow-up of 9.1 years. Negative control correction revealed anticholinergic antidepressant use was associated with increased risk of cardiovascular events (HD

conclusionsAnticholinergic antidepressants may increase the risk of cardiovascular events compared with non-anticholinergic antidepressants. These findings underscore prioritizing therapeutic options with a lower anticholinergic burden in clinical practice.

Indexed as

Antidepressive AgentsCardiovascular DiseasesCholinergic AntagonistsAdultAgedFemaleHospitalizationHumansMaleMiddle AgedPropensity ScoreUK BiobankUnited KingdomAntidepressive AgentsCholinergic Antagonistsanticholinergicsantidepressantcardiovascular eventnegative control

Identifiers

PMID42449494
PMCPMC13369797

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.