People who use drugs with anticholinergic effects, including certain anti-depressants, drugs for urinary incontinence and common antihistamines, could have a higher risk of developing cardiovascular disease, suggest scientists from Sweden’s Karolinska Institutet in BMC Medicine.
Anticholinergic drugs reduce the effect of the neurotransmitter acetylcholine and are commonly prescribed to middle-aged and older people. This large group of drugs includes antihistamines for allergic conditions, anxiety or insomnia, drugs for urinary incontinence, and certain anti-depressants, where tricyclic anti-depressants have a strong anti-cholinergic effect, whereas SSRIs have a weaker effect.
A high cumulative use of these drugs, referred to as anti-cholinergic burden, has previously been linked to impaired cognitive ability.
Anti-cholinergic drugs in the study were identified based on the Anticholinergic Cognitive Burden (ACB) scale, a tool used in research and clinical contexts. The scale covers a wide range of different drugs that are scored between 1 and 3, depending on how much the drug blocks the neurotransmitter acetylcholine.
The consumption of these drugs is added up to estimate a patient’s anti-cholinergic burden.
May affect heart regulation
This latest study suggests that the drugs may also affect the parasympathetic nervous system and thereby the regulation of the cardiovascular system. The results show that it may be important to monitor the total drug burden in everyday clinical practice.
The research included more than 500 000 people in Stockholm who were 45 or older with no prior cardiovascular disease, except for hypertension, at the start of the study. The teams followed the participants for up to 14 years and analysed how the use of anticholinergic drugs was associated with the development of cardiovascular disease.
“Many of these drugs are used by older people and those with multiple medical conditions. We wanted to investigate whether the total exposure had any significance for the risk of developing cardiovascular disease over time,” said Nanbo Zhu, postdoctoral researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.
More exposure, 71% more risk
The study showed that the risk of cardiovascular disease increased in line with how much anti-cholinergic medication the participants used each year. Those with the highest exposure had a 71% higher risk than people who did not use anti-cholinergic medication at all.
The association was seen for all types of cardiovascular disease but was particularly clear for heart failure and various forms of arrhythmia.
“Our results indicate that the cumulative drug burden can affect heart regulation, not only in the short term but also over the long term. This does not mean that the drugs should always be avoided, but that exposure should be monitored carefully,” said Hong Xu, Assistant Professor at the Department of Neurobiology, Care Sciences and Society.
The researchers pointed out that the study is observational, meaning it cannot establish a causal relationship. Other factors, such as underlying diseases, may also influence the associations.
The work was carried out within the Stockholm CREAtinine Measurements project in collaboration between several research groups at Karolinska Institutet and Region Stockholm.
Study details
Anticholinergic drug burden and incident cardiovascular events: a population-based study
Nanbo Zhu, Maria Eriksdotter, Bahira Shahim, Kristina Johnell, Sara Garcia-Ptacek, Juan-Jesus Carrero, Hong Xu.
Published online for BMC Medicine on 28 February 2026
Abstract
Background
Drugs with anticholinergic properties are commonly used in older adults for various medical conditions, but the long-term cardiovascular consequences of cumulative exposure have not been well established. This study aims to examine whether cumulative anticholinergic drug burden is associated with incident cardiovascular events.
Methods
The large population-based cohort study included 508 273 Stockholm residents aged ≥ 45 years on January 1, 2008, who had no history of major cardiovascular diseases, with follow-up until December 31, 2021. Anticholinergic burden was assessed using the Anticholinergic Cognitive Burden scale and quantified as annual consumption in defined daily doses (DDDs). Inverse probability-weighted Cox proportional hazards models were used to estimate the weighted hazard ratio (HR) and 95% confidence interval (CI) for the associations between both baseline and time-varying exposure and incident cardiovascular events, overall and by disease subtypes.
Results
A total of 118,266 incident cardiovascular events were recorded during a median follow-up of 14.0 years. Higher levels of anti-cholinergic drug exposure were significantly associated with an increased risk of cardiovascular events after adjusting for socio-demographic, lifestyle, and clinical risk factors in both baseline and time-updated models, with stronger associations observed in the latter. In the time-updated model, the HR (95% CI) increased with annual cumulative exposure: 1.16 (1.13, 1.20) for 1–89 DDDs, 1.31 (1.28, 1.34) for 90–364 DDDs, and 1.71 (1.67, 1.76) for ≥ 365 DDDs. A significant dose–response relationship was observed across event subtypes. In the highest exposure group, the HR (95% CI) was 2.70 (2.57, 2.84) for heart failure, 2.17 (2.08, 2.27) for arrhythmias, 1.48 (1.34, 1.63) for artery disease, 1.32 (1.21, 1.43) for venous thromboembolism, 1.46 (1.37, 1.55) for myocardial infarction, and 1.32 (1.25, 1.39) for cerebrovascular disease. Results were consistent in subgroups and sensitivity analyses.
Conclusions
These findings highlight the potential cardiovascular harms of anticholinergic drug burden in middle-aged and older adults and underscore the need for careful prescribing and monitoring of such medications.
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