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Randomized Controlled Trial
. 2024 Sep 16;37(10):826-836.
doi: 10.1093/ajh/hpae059.

Effect of Therapeutic Drug Monitoring on Adherence and Blood Pressure: A Multicenter Randomized Clinical Trial

Lene V Halvorsen  1   2   3 , Camilla L Søraas  2   4 , Anne Cecilie K Larstorp  2   3   5 , Ulla Hjørnholm  2 , Vibeke N Kjær  2 , Knut Liestøl  6 , Arleen Aune  7   8 , Eirik Olsen  9   10 , Karl Marius Brobak  11   12 , Ola U Bergland  2 , Stine Rognstad  2   3   13 , Nikolai R Aarskog  2   3   14 , Sondre Heimark  1   2   3 , Fadl Elmula M Fadl Elmula  2 , Eva Gerdts  7   8 , Rune Mo  10   15 , Marit D Solbu  11   12 , Mimi S Opdal  3   13 , Sverre E Kjeldsen  1   2   3   16 , Morten Rostrup  2   14   17 , Aud Høieggen  1   2   3
Affiliations
Randomized Controlled Trial

Effect of Therapeutic Drug Monitoring on Adherence and Blood Pressure: A Multicenter Randomized Clinical Trial

Lene V Halvorsen et al. Am J Hypertens. .

Abstract

Background: Drug concentration in blood or urine is an acknowledged method to detect nonadherence. Observational studies suggest that informing patients about low or absent serum drug levels improves blood pressure (BP). We performed a multicenter randomized clinical trial to test the hypothesis that therapeutic drug monitoring (TDM) could improve drug adherence and BP in patients with uncontrolled hypertension (HT).

Methods: Patients were ≥18 years on stable treatment with at least 2 antihypertensive agents. We planned to randomize 80 nonadherent patients with a systolic daytime ambulatory BP ≥135 mm Hg to TDM intervention or not. The control group and the study personnel who measured BP remained uninformed about serum drug measurements throughout. All patients and physicians were blinded for BPs. Lifestyle advice and detailed information on the disease process and the importance of BP treatment were given to both groups.

Results: From 2017 to 2022, we randomized 46 diagnosed nonadherent from a total of 606 patients with uncontrolled HT. The TDM group had a 6.7 (±14.5) mm Hg reduction from 147.9 (±10.3) to 141.1 (±14.1) mm Hg, and the control group experienced a 7.3 (±13.2) mm Hg reduction from 147.1 (±9.2) to 139.1 (±17.4) mm Hg, P = 0.9 between groups. Adherence improved in both groups, 73% in the TDM group and 59% in the control group became adherent at 3 months, P = 0.51.

Conclusions: In our prospective multicenter clinical trial of uncontrolled and nonadherent hypertensive patients, we found no additional effect of TDM on BP and drug adherence compared with standard care.

Clinical trials registration: Trial Number NCT03209154, www.clinicaltrials.gov.

Keywords: adherence; antihypertensive drugs; blood pressure; hypertension; nonadherence; randomized clinical trial; therapeutic drug monitoring.

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Conflict of interest statement

S.E.K. reports lecture honoraria from Getz, Emcure, JB Pharma, Merck KGaA, Vector-Intas, and Zydus. A.H. reports lecture honoraria from AstraZeneca. The other authors report no disclosures.

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Study design. Abbreviations: ABPM, ambulatory blood pressure measurement; ECG, electrocardiogram; TDM, therapeutic drug monitoring; UHPLC–MS/MS, ultra-high-performance liquid chromatography–tandem mass spectrometry.
Figure 2.
Figure 2.
Patient flowchart. Abbreviations: ABPM, ambulatory blood pressure measurement; BP, blood pressure; RCT, randomized controlled trial; SAE, serious adverse event; TDM-info, standardized information on the patients’ serum concentrations, the intervention. aThese 2 patients had uncontrolled hypertension and were invited to the baseline visit, however, they were misclassified as adherent, thus not randomized and their antihypertensive medication was instead changed. A reevaluation by the pharmacologist disclosed that the serum drug concentrations did not match the evaluation and their adherence status was corrected to nonadherent, but they were no longer eligible for the RCT.
Figure 3.
Figure 3.
Individual patient data for the primary endpoint. Change in systolic daytime ABPM during 3 months in the intervention (solid line) and control (dotted line) groups. Visits are marked on the X-axis, and SBP on the Y-axis (mm Hg). The Y-axis is truncated. Abbreviations: ABPM, ambulatory blood pressure measurement; SBP, systolic blood pressure.
Figure 4.
Figure 4.
Daytime ABPM and adherence during 6-month follow-up. Panel a: Mean blood pressure (mm Hg) is shown on the Y-axis (truncated). TDM group in red and the control group in blue. Visits are marked on the X-axis. Daytime systolic ABPM (P = 0.43)a and diastolic ABPM (P = 0.34)b did not differ between the groups over time (ANOVA). Panel b: The number of patients is shown on the Y-axis, those attending the visit in red (TDM group) or blue (control group), and the number of adherent patients in the squared pattern. Differences between groups are not significant with Fisher’s exact test. Abbreviations: ABPM, ambulatory blood pressure measurement; ANOVA, analysis of variance; DBP, diastolic blood pressure; SBP, systolic blood pressure; TDM-info, standardized information on the patients’ serum concentrations.
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