Persistence with Antihypertensive Drugs in Patients with Hypertension and Dementia in Germany

INTRODUCTION

Hypertension, also known as high blood pressure, is involved in 7.5 million deaths worldwide every year, accounting for approximately 12.8% of all deaths [1]. In Germany, hypertension is found in around one out of every three individuals [2], and is associated with significant health care costs [3].

Hypertension, a chronic disease that has a major impact on the cardiovascular system, is often a result of aging and its related physiopathological dysregulation [4]. Therefore, many patients with hypertension are also affected by other diseases, in particular dementia [5 –7]. This psychiatric condition leads to a decrease in mental abilities, such as memory and concentration, and indirectly impairs patient’s persistence with therapy. To date, few authors have studied the impact of dementia on persistence with antihypertensive drugs. In 2009, it was found in an international study that dementia had no significant effect on non-persistence with antihypertensive treatments in Pennsylvania, British Columbia, and the Netherlands [8]. In contrast, in 2014, Mancia et al. showed in almost 500,000 patients receiving antihypertensive prescriptions that dementia was associated with a significant increase in the risk of therapy discontinuation [9]. More recently, Ah and colleagues discovered in more than 45,000 people that dementia had a positive impact on both adherence and persistence [10]. Although these three studies are of great interest, the association between dementia and persistence with antihypertensive drugs remains controversial.

Therefore, the goal of the present retrospective study was to analyze persistence with antihypertensive drugs in patients affected by hypertension and dementia in Germany.

METHODS

Study population

This study included hypertension patients who were initially treated with antihypertensive drugs in 1,262 general practices in Germany between January 2013 and December 2015 (index date). To be included, individuals also had to be followed for at least 12 months prior to the index date. These patients were classified as either patients with or without a diagnosis of dementia (ICD-10: F01, F03, G30) at baseline.

To control for confounding, one-to-one matching was carried out based on a propensity score that was constructed as the conditional probability of dementia as a function of age, gender, type of residence (nursing home versus home-care setting), physician, and initial antihypertensive therapy (logistic regression). First dementia patients were selected at random. Greedy matching was used by choosing a patient without dementia whose propensity score was closest to that of this randomly selected dementia subject for matching (Fig. 1).

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Fig.1

Flow chart of patients included in the study.

RESULTS

Patient characteristics are displayed in Table 1. After matching, the study included 2,191 patients with hypertension and dementia and 2,191 patients with hypertension but without dementia. The mean age was 79.3 years (SD = 10.3 years) in both groups. In the dementia group, 37.3% were men and in the non-dementia group 38.0% were men. Hyperlipidemia was the most frequent co-diagnosis in patients diagnosed with dementia (31.5%), as well as in those without this psychiatric condition (30.8%). Twelve months after initiating antihypertensive therapy, 73.5% of cases and 69.5% of controls were persistent (log-rank p-value <0.001, Fig. 2). The results of the Cox regression analyses are shown in Table 2. Dementia was associated with a significant decrease in the risk of non-persistence with antihypertensive drugs in the entire population (HR = 0.86, 95% CI: 0.79–0.93). This finding was corroborated in five different subgroups (age ≤60 years, age 61–70 years, men, women, and patients living in home-care settings).

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Fig.2

Kaplan–Meier curves for persistence with antihypertensive treatment in hypertension patients with and without dementia in Germany.

DISCUSSION

In the present study of 4,382 individuals followed in general practices in Germany, we discovered that the one-year persistence with antihypertensive therapy was higher in patients with both hypertension and dementia compared to patients with hypertension but without dementia. Furthermore, subsequent regression analyses showed that dementia was negatively associated with the risk of disrupting antihypertensive therapy.

In recent years, several studies have focused on the impact of dementia on non-persistence with antihypertensive drugs. In 2008, van Wijk and colleagues discovered in almost 60,000 elderly patients from Pennsylvania (USA), British Columbia (Canada), and the Netherlands that the share of individuals with at least 180 days without antihypertensive medication was between 23.3% and 24.0% one year after treatment initiation, with such non-persistence increasing to 36.3–41.1% after six year [8]. The authors estimated that predictors of non-persistence in the first 12 months of therapy were older age, male gender, and frequent use of prescribed medications. In contrast, a history of acute myocardial infarction and hypercholesterolemia were protective factors in the three different countries, as was angina pectoris in the Netherlands only. Interestingly, dementia had no significant impact on persistence in the three different regions, with hazard of between 0.92 and 1.03. Since less than 5% of the elderly included in this study were affected by dementia, the absence of a significant association between this chronic disorder and antihypertensive therapy can potentially be explained by a lack of power of the statistical analysis.

Later, in 2014, an Italian study including 493,623 new users of antihypertensive drugs showed that 57% of the population discontinued treatment within the year following initiation, discontinuation being defined as a lack of prescription renewal for at least 3 months [9]. Mancia and colleagues further discovered that the adjusted risk of non-persistence was associated with both patient and drug characteristics, as men, older individuals, patients with antidiabetic agents, and those hospitalized for cardiovascular or renal disease were less likely to be non-persistent. In contrast, the risk of discontinuation was higher in people who were prescribed antidepressants or were hospitalized for concomitant pulmonary, rheumatic, neoplastic, and neuropsychiatric diseases, such as dementia. Contrary to this last result, in the present work we found that dementia protected against the risk of non-persistence in people who were prescribed antihypertensive drugs. One major difference potentially explaining the discrepancy in these findings is that the present study focused on all-cause dementia, whereas Mancia et al. examined dementia diagnoses that required at least one hospitalization [9]. Therefore, the dementia patients included in their study may have displayed more severe forms of the disease than patients included in this German retrospective work. It is also worth mentioning that study populations were different, as the target individuals of the 2014 analysis were National Health Service beneficiaries aged 40–80 years who lived in Lombardy [9], whereas patients included in our study were adults followed in general practices, with or without private health insurance, who lived in Western or Eastern Germany.

More recently, a South Korean study including 45,787 newly treated uncomplicated hypertensive individuals investigated one-year persistence with antihypertensive therapy [10]. The researchers found that 62.1% of patients were persistent. Furthermore, Ah and colleagues showed that individuals aged 80 years or older were at a particular risk of discontinuation, whereas women and patients affected by dementia or dyslipidemia displayed a significantly lower risk. This finding may be explained by the fact that people suffering from dementia are surrounded by their family, which may result in better management and treatment of hypertension. In line with this hypothesis, it was previously discovered in a meta-analysis including 122 studies that adherence and treatment are favored by available family support [15]. In 2016, Ojo and colleagues also found in 360 patients with hypertension that strong family support is an independent predictor of controlled blood pressures [16]. In addition to family, physicians, nurses, and other health professionals play a key role in the management and treatment of patients with hypertension. In 2015, Parro-Moreno et al. showed that a favorable clinical practice environment and a high number of patient-nurse consultations contributed to better hypertension control [17].

Retrospective primary care database analyses are generally limited by the validity and completeness of the data on which they are based. The present study was subject to several limitations, which should be mentioned at this point. First, no valid information was provided on dementia severity and degree of dependency. Furthermore, the assessment of complications and comorbidities relied solely on ICD codes entered by primary care physicians. Data on socioeconomic status (e.g., education and income) and lifestyle-related risk factors (e.g., smoking, alcohol, and physical activity) were also lacking. Unfortunately, the documentation of hypotension was also insufficient and could not be used, although hypotension may have had an impact on treatment persistence. One strength of the study was the large nationwide database. Another strength was the use of real-world data on diagnoses in primary care practices where diagnoses are continuously documented, allowing unbiased exposure assessment (no recall bias).

Overall, the present study indicates that dementia is associated with a decrease in the risk of non-persistence with antihypertensive drugs in patients followed in general practices in Germany. In the future, it would be interesting to focus on the impact of family and friends on treatment persistence in patients with both dementia and hypertension.