Antihypertensive drug concentration measurement combined with personalized feedback in resistant hypertension: a randomized controlled trial

Laura E.J. Peeters*, M. H.W. Kappers, D. A. Hesselink, J. B. Van Der Net, S. C.C. Hartong, R. Van De Laar, M. Ezzahti, P. J.G. Van De Ven, I. M. Van Der Meer, E. L.E. De Bruijne, A. A. Kroon, S. Indhirajanti-Tomasoa, N. A.J. Van Der Linde, S. Bahmany, E. Boersma, E. K. Massey, L. Van Dijk, T. Van Gelder, Birgit C.P. Koch, Jorie Versmissen

*Corresponding author for this work

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Adherence to antihypertensive drugs (AHDs) is crucial for controlling blood pressure (BP). We aimed to determine the effectiveness of measuring AHD concentrations using a dried blood spot (DBS) sampling method to identify nonadherence, combined with personalized feedback, in reducing resistant hypertension.


We conducted a multicenter, randomized, controlled trial (RHYME-RCT, ICTRP NTR6914) in patients with established resistant hypertension. Patients were randomized to receive either an intervention with standard of care (SoC) or SoC alone. SoC consisted of BP measurement and DBS sampling at baseline, 3 months (t3), 6 months (t6), and 12 months (t12); AHD concentrations were measured but not reported in this arm. In the intervention arm, results on AHD concentrations were discussed during a personalized feedback conversation at baseline and t3. Study endpoints included the proportion of patients with RH and AHD adherence at t12.


Forty-nine patients were randomized to receive the intervention+SoC, and 51 were randomized to receive SoC alone. The proportion of adherent patients improved from 70.0 to 92.5% in the intervention+SoC arm (P = 0.008, n = 40) and remained the same in the SoC arm (71.4%, n = 42). The difference in adherence between the arms was statistically significant (P = 0.014). The prevalence of resistant hypertension decreased to 75.0% in the intervention+SoC arm (P < 0.001, n = 40) and 59.5% in the SoC arm (P < 0.001, n = 42) at t12; the difference between the arms was statistically nonsignificant (P = 0.14).


Personalized feedback conversations based on DBS-derived AHD concentrations improved AHD adherence but did not reduce the prevalence of RH.

Original languageEnglish
Pages (from-to)169-178
Number of pages10
JournalJournal of Hypertension
Issue number1
Publication statusPublished - Jan 2024

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