People who use drugs with anticholinergic effects, including certain antidepressants, drugs for urinary incontinence and common antihistamines, are at higher risk of developing cardiovascular disease. This is shown in a new study from Karolinska Institutet published 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 used for allergic conditions, anxiety or insomnia, drugs for urinary incontinence, and certain antidepressants, where tricyclic antidepressants have a strong anticholinergic effect, whereas SSRIs have a weaker effect. A high cumulative use of these drugs, referred to as anticholinergic burden (see fact box), has previously been linked to impaired cognitive ability.

May affect heart regulation

The new 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 study included more than 500,000 people in Stockholm, Sweden, who were 45 years of age or older and had no prior cardiovascular disease, except for hypertension, at the start of the study. The researchers 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 by people with multiple medical conditions. We wanted to investigate whether the total exposure had any significance for the risk of developing cardiovascular disease over time,” says Nanbo Zhu, postdoctoral researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.

71 per cent higher cardiac risk

The study showed that the risk of cardiovascular disease increased in line with how much anticholinergic medication the participants used each year. Those with the highest exposure had a 71 per cent higher risk of a cardiovascular event than people who did not use anticholinergic 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,” says Hong Xu, assistant professor at the Department of Neurobiology, Care Sciences and Society.

The researchers point 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. The study was funded by the Swedish Research Council, the Center for Innovative Medicine Foundation, and other foundations. Some researchers report assignments for the pharmaceutical industry, which are disclosed in the scientific publication.

Facts about the drugs

Anticholinergic 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 anticholinergic burden. The drugs included in ACB are listed in table S1 in the study's supplementary information.