Adequate controlled blood pressure decreases the risk of cardiovascular events. However, the elderly are more vulnerable and thereby more prone to side effects of antihypertensive drugs. A lack of pharmacokinetic and pharmacodynamic (PK/ PD) studies in older patients makes specific and tailored advices towards antihypertensive drug therapy difficult. The aim of our study, DiffErenCes In antihypertenSive drug levels In patients with hypertensiON (DECISION), is to fill in this PK/ PD knowledge gap and move towards precision dosing. DECISION is a prospective observational PK/PD study set up to determine the difference in exposure to the antihypertensive drugs, losartan and perindopril, measured by drug levels in blood. The area under the curve (AUC; PK) and furthermore the association between the AUC and the effect on blood pressure (PD) will be compared between elderly and younger patients.

Background Older patients using antihypertensive medication may experience Adverse Drug Events (ADEs), and thus benefit from deprescribing. The lack of a practical protocol may hamper deprescribing. Therefore, we aimed to develop a deprescribing protocol, based on a review of literature, combined with a feasibility test in a small number of patients. Methods A deprescribing protocol for general practitioners was drafted and tested in older patients using multiple antihypertensive medication in a single arm intervention. Patients were included if they were 75 years or older, were using two or more antihypertensives, had at least one ADE linked to antihypertensive medication and deprescribing was considered to be safe by their general practitioner. The primary outcome was the percentage of patients for whom one or more antihypertensive drugs were stopped or reduced in dose after 12 months of follow up while maintaining safe blood pressures. Secondary outcomes were the proportion of patients reporting no ADEs after 12 months and the number of deprescribed antihypertensives. Patient’s opinions on deprescribing and enablers and barriers for study participation were also collected. Results Nine general practitioners included 14 patients to deprescribe antihypertensive medication using the deprescribing protocol. After 12 months antihypertensive drug use was lowered in 11 patients (79%). These patients had a mean systolic blood pressure increase of 16 mmHg and a mean diastolic blood pressure increase of 8 mmHg. Nine patients (64%) reported experiencing no ADEs anymore after twelve months. The mean number of deprescribed antihypertensives was 1.1 in all patients and 1.4 (range: 0.5 to 3.5) in patients who successfully lowered their medication. At baseline, being able to use less medication was the most frequently mentioned enabler to participate in this study. The most frequently mentioned positive experience at the end of the study was using less medication, which was in line with the most mentioned enabler to participate in this study. Conclusion A protocol for deprescribing antihypertensives in older patients was considered feasible, as it resulted in a substantial degree of safe deprescribing in this pilot study. Larger studies are needed to demonstrate the effect and safety of deprescribing antihypertensives in older patients.

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