Prevalence of Use of Cardiovascular Drugs in Dementia Patients Treated in General Practices in Germany

INTRODUCTION

Dementia is a psychiatric condition that involves neurodegeneration and is characterized by a loss of cognitive functions, which leads to a decrease in the quality of life of the patient [1]. Around 48 million people in the world have dementia, and this number is set to increase to approximately 76 million by 2030 and to exceed 130 million by 2050 [1, 2]. In Germany, dementia has been found in 1.2 million individuals, and around 200,000 new cases are diagnosed each year [3]. Therefore, this psychiatric disorder has a major impact on health in this country.

Dementia is a chronic disease associated with numerous cardiovascular disorders (CVDs), such as hypertension, dyslipidemia, and atrial fibrillation [4–6]. Although dementia and CVDs are both related to aging, one has to bear in mind that CVDs can have a direct impact on the development of dementia, as it can alter brain function. Therefore, dementia patients are also commonly affected by CVDs and frequently receive cardiovascular medications. Currently, few studies have aimed to estimate the prevalence of the use of these drugs in dementia patients. In 2014, Welsh et al. performed a systematic review of observational studies on the treatment of hypertension in people with dementia [7]. The authors showed that 45% of dementia patients suffered from hypertension and that 73% of them were receiving at least one antihypertensive drug. The same year, Cermakova and colleagues further found that cardiovascular medication was extensively used across dementia disorders, more particularly in vascular and mixed dementia [8]. In line with these findings, another Swedish work found that cardiovascular comorbidities were very frequent in these two types of dementia [9].

Although these findings have shed some light on the share of dementia patients receiving cardiovascular treatments, little is known about this share in Germany. Therefore, the goal of the present study was to analyze the prevalence of the use of these medications in patients affected by dementia and treated by general practitioners in Germany.

METHODS

RESULTS

Patient characteristics are displayed in Table 1. Of a total of 9,225 dementia patients, 7,987 had been prescribed cardiovascular drugs (CVD group), and 1,268 had not been prescribed cardiovascular drugs (non-CVD group). Mean age was 82.5 years (SD = 7.8 years) in CVD patients and 79.8 years (SD = 10.1 years) in non-CVD patients. The percentage of men was 34.0% and 37.8% in the CVD and non-CVD groups, respectively. Unspecified dementia was the most frequent type of dementia (CVD patients: 52.3%, and non-CVD patients: 50.5%). The most frequent co-diagnoses were hypertension (CVD group: 88.9%, and non-CVD group: 43.1%), hyperlipidemia (52.3% and 29.5%), and diabetes (44.5% and 25.6%). Figure 1 shows the prevalence of cardiovascular drug use in dementia patients. The share of individuals receiving such treatments was 86.3%. It increases from 72.5% in people aged 70 years or younger to 88.0% in people over the age of 90. This share was similar between men (85.0%) and women (87.0%). Furthermore, the prevalence of cardiovascular drug use was higher in patients with vascular dementia (89.8%) or unspecified dementia (86.7%) than in Alzheimer’s disease (83.1%). Finally, the prescription of cardiovascular drugs was particularly frequent in individuals diagnosed with heart failure (94.9%), cardiac arrhythmias (94.5%), or ischemic heart diseases (94.3%). Figure 2 displays the share of the different classes of cardiovascular drugs prescribed to dementia patients. Diuretics (20.9%), beta blocking agents (20.0%), and ACE inhibitors (17.4%) were the three most commonly prescribed families of drugs. The results of the multivariate logistic regression analysis are shown in Table 2. Patients between the ages of 71–80 (OR = 1.59), 81–90 (OR = 1.61), and over the age of 90 (OR = 1.48) were more likely to receive cardiovascular drugs than patients under the age of 71. Moreover, individuals with Alzheimer’s disease had a lower chance of being prescribed these drugs than individuals with unspecified dementia (OR = 0.81), whereas individuals with vascular dementia had a higher chance (OR = 1.22). We found a positive association between the use of cardiovascular drugs and all co-diagnoses: diabetes, hypertension, hyperlipidemia, ischemic heart diseases, cardiac arrhythmias, heart failure, and cerebrovascular diseases (ORs ranging from 1.23 to 7.12). Finally, gender was not significantly associated with the likelihood to be prescribed cardiovascular drugs.

DISCUSSION

In the present German retrospective study, around 86% of dementia patients received cardiovascular drugs, the most frequent of which were diuretics, beta blocking agents, and ACE inhibitors. The multivariate regression analysis showed that older patients were more likely to be prescribed cardiovascular medications than younger patients. The share of the use of these drugs was also higher in individuals diagnosed with vascular dementia than in individuals diagnosed with Alzheimer’s disease or unspecified dementia. Finally, we found a strong positive association between cardiovascular prescriptions and hypertension, heart failure, and cardiac arrhythmias.

The relationship between dementia and cardiovascular disorders has been known for decades [4–6, 13–15]. In 2010, Bunch and colleagues discovered in approximately 37,000 individuals that atrial fibrillation was independently associated with all forms of dementia [4]. Interestingly, the highest risk was in the youngest group, suggesting that aging is not the only factor to explain the relationship between these disorders. Furthermore, they suggested that the risk of mortality was increased by developing atrial fibrillation after a diagnosis of dementia. In line with these findings, other works have found a close relationship between dementia and cardiovascular conditions [5, 6]. Therefore, the prescription of cardiovascular drugs is frequent in dementiapatients.

To date, few studies have investigated the prevalence of cardiovascular drug use in people with dementia. In 2010, Müther and colleagues aimed to compare the treatment of hypertension, diabetes, and hyperlipidemia in patients with and without dementia in Germany [16]. Although the share of dementia patients with antihypertensive prescriptions was high and exceeded 85%, it was suggested that this prescription rate tended to be lower in the dementia population than in the non-dementia population. Later, a 2014 UK meta-analysis of 13 observational studies discovered that hypertension occurred in 45% of dementia patients [7]. Furthermore, approximately three out of four patients affected by both dementia and hypertension received at least one antihypertensive drug, with diuretics (64%), calcium channel blockers (43%), and angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (42%) being the most commonly prescribed drugs. In addition, two studies included in this meta-analysis estimated that the mean number of antihypertensive medications per patient was 2.4 [17, 18]. Although the findings of this work are of great interest, a non-negligible heterogeneity was found between the 13 studies available for the analysis. In fact, these studies were performed between 1990 and 2014 in different countries, included various numbers of patients, and were conducted in different settings (mainly hospitals, institutions, and communities). Therefore, the findings of the work of Welsh et al. should be interpreted with caution [7].

That same year, Cermakova and colleagues estimated the prevalence of the use of cardiovascular drugs in dementia patients in Sweden [8]. In this study, Alzheimer’s disease was the most frequent type of dementia (41%), followed by mixed (27%), and vascular dementia (25%). Around 70% of the population used cardiovascular drugs. These drugs were most common among individuals diagnosed with vascular dementia (84%) and least common among individuals diagnosed with Alzheimer’s disease (59%). In their adjusted logistic regression analysis, the authors found that people affected by vascular or mixed dementia and men were more likely to be prescribed cardiovascular drugs than people affected by Alzheimer’s disease and women. Furthermore, age, Mini-Mental State Examination (MMSE) scores, and the total number of drugs were positively associated with the use of cardiovascular medications. In contrast, living alone was found to have a negative impact on the likelihood of being prescribed such drugs. The present German retrospective work corroborated these previous findings, as patients with vascular dementia and older people were more likely to use cardiovascular drugs than patients with other types of dementia and younger people. Nevertheless, this study found no significant association between gender and the prescription of cardiovascular medications. Although such discrepancy must be carefully analyzed and discussed, one has to bear in mind that the study of Cermakova and colleagues did not include potential comorbidities in their regression model [8]. Therefore, the association they found between gender and cardiovascular drug use may have been biased by certain confounders. Another explanation is Sweden and Germany may differ in regard to this issue, which could result in different prescription patterns for cardiovascular treatments in patients with dementia. Moreover, the share of dementia patients using cardiovascular drugs in Germany was higher than in Sweden. One of the reasons for higher use of cardiovascular drugs in Germany could be the higher share of patients with cardiovascular diseases. In Sweden, ischemic heart disease was present in 23% of all patients with dementia, and heart failure in 15% [19]. In Germany, ischemic heart disease was diagnosed in 40% and heart failure in 34% of dementia patients. In the study of Garre-Olmo et al. analyzing dementia patients in the Registry of Dementias of Girona, Spain, 78.9% of dementia patients used cardiovascular drugs [20]. This share is slightly smaller than the prevalence of cardiovascular drug use in Germany, however, cardiovascular drugs did not include peripheral vasodilators (ATC: C04) and vasoprotectives (ATC: C05) in the Spanishwork.

As previously stated, patients affected by medical comorbidities were more likely to be prescribed cardiovascular drugs than patients free of such comorbidities. This association highlights the fact that such medications are used for curative rather than preventive treatments. Of particular interest was hypertension, which led to a 7-fold increase in the likelihood of being prescribed cardiovascular drugs. This finding corroborates the results of Welsh and colleagues, who found that most dementia patients diagnosed with hypertension are prescribed antihypertensives [7]. Finally, the most frequently prescribed families of drugs were diuretics, beta blocking agents, and ACE inhibitors. Despite some concerns in the past about the efficacy and safety of these drugs in the elderly [21–23], one can hope that these treatments may have an indirect impact on dementia. In fact, it was discovered in a postmortem study including 291 individuals that the use of antihypertensives was associated with a positive effect on Alzheimer’s disease neuropathology [24].

This study had several limitations. First, the assessment of dementia diagnoses and co-morbidities was based solely on ICD codes entered by GPs. There was a lack of information on how dementia was diagnosed (i.e., diagnostic criteria or assessment tools). No data from neuropsychiatric practices were analyzed because the documentation of co-morbidities such as diabetes, hypertension, and coronary heart disease by neuropsychiatrists was often missing. Furthermore, data on socioeconomic status were not available.

Overall, the present German study, which included more than 9,000 dementia patients treated in general practices, showed that 86% of them were prescribed cardiovascular drugs. The use of these medications was significantly associated with age, type of dementia, and co-diagnoses. Additional studies are needed to corroborate these findings in other settings.

DISCLOSURE STATEMENT

Authors’ disclosures available online (http://j-alz.com/manuscript-disclosures/16-1234r1).