Can serum consentration measurements of antihypertensive drugs improve blood pressure control? a multicenter double blinded randomized controlled trial

Objective: Drug concentration in urine or serum using liquid chromatography coupled to mass-spectrometry (UHPLC-MS/MS) may disclose non-adherence. Whether this direct method will improve adherence is still unknown. In this multicenter randomized controlled trial with a double-blinded approach, we aimed to investigate if measurements and standardized information about serum concentrations of antihypertensive drugs (therapeutic drug monitoring (TDM)), could improve blood pressure (BP) control in documented non-adherent hypertensive patients. Design and method: Patients were > = 18 years old with eGFR >30 mL/min/1.73m 2 , prescribed > = 2 antihypertensive agents and on a stable treatment regimen for at least 4 weeks. Experienced pharmacologists assessed adherence status based on serum drug concentrations, dose and patient-reported time since last intake of the drugs. Patients received no information regarding use of blood samples to screen for non-adherence. The ethics committee approved the study. All patients signed written informed consent. Non-adherent patients with a systolic daytime ambulatory BP (ABPM) > = 135 mmHg were randomized 1:1 to TDM-intervention or not. The number of visits during 6 months follow-up were equal in both groups and antihypertensive medication regimens remained unchanged. Standardized TDM-information was given to the intervention-group at baseline and after 1 and 3 months. The control group remained uninformed about serum drug measurements until after completion of the study. Life style advice and information on necessity of BP treatment, how to remember to take medications and potential hypertension mediated end-organ damage were given to both groups. Investigators and patients were masked for BPs, and separate personnel measuring BPs were blinded to randomization group. Results: From 2017 to 2022, 606 patients (52.3%) of 1159 patients investigated had uncontrolled HT. The non-adherent patients were younger (57.8 vs 64.0 years, p < 0.001), duration of hypertension was shorter (12 vs 16 years, p = 0.024) and daytime diastolic ABPM (90 vs 84 mmHg, p < 0.001) and heart rate (76 vs 70 bpm, p < 0.001) were higher. Uncontrolled and non-adherent patients were enrolled into the subsequent randomized study performed with a double-blinded approach. Conclusions: There was no difference in the primary end-point, daytime systolic ABPM at 3 months, between TDM and control group (-6.7 vs -7.3 mmHg, p = 0.897).