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Randomized Controlled Trial
. 2025 Jul 2;26(1):212.
doi: 10.1186/s12875-025-02885-z.

STEPWISE management of clinically apparent resistant hypertension in primary care: a cluster randomised controlled trial

Birsen Kiliç  1 , Marion C J Biermans  2 , Michiel L Bots  3 , Mark van der Wel  2 , Wim J C de Grauw  2 , Frans H Rutten  1 , Monika Hollander  4   5
Affiliations
Randomized Controlled Trial

STEPWISE management of clinically apparent resistant hypertension in primary care: a cluster randomised controlled trial

Birsen Kiliç et al. BMC Prim Care. .

Abstract

Background: Clinically apparent resistant hypertension (CARH) is common and a major health problem because it increases the risk of cardiovascular events. We aim to assess whether a stepwise work-up management strategy for patients with CARH in primary care would result in better blood pressure control compared to usual care.

Methods: A pragmatic, cluster-randomised controlled trial (cRCT). General practitioners (GPs) from 22 practices (10 intervention arm; 12 usual care) recruited 106 patients aged 18-80 years who had an office blood pressure (BP) > 140/90 mmHg and were prescribed three or more antihypertensive drugs from different therapeutic classes for three or more months in an adequate dose. This study was conducted between October 2018 and June 2021. The intervention was a stepwise approach comprising of (i) 24-hour blood pressure measurements, (ii) dedicated attention on intake of blood pressure raising compounds, (iii) on lifestyle and on compliance to and (iv) optimalisation of medication, and (v) referral to specialist care, when appropriate. The control group received usual care. Primary outcome was the difference in 24-hours systolic BP between intervention and usual care measured at 8 months after baseline.

Results: Neither 24-hour nor office systolic BP 8 months after baseline significantly differed between intervention and usual care arm: 136.9 mmHg versus 132.6 mmHg (p = 0.15) and 146.1 mmHg versus 147.6 mmHg (p = 0.51), respectively. No significant differences across groups were seen in number of prescribed BP lowering medication: 2.98 versus 3.11, or controlled hypertension after 8 months: 22% versus 28%.

Conclusions: Our results suggest that a pragmatic, structured stepwise approach of CARH does not result in lower 24 h or office BP values compared to usual primary care.

Trial registration: NTR7304 (www.trialregister.nl/trial/7099), May 4th, 2018.

Keywords: Antihypertensives; Cardiovascular disease; Cardiovascular risk; Clinically apparent resistant hypertension; Cluster randomised controlled trial; General practice; Hypertension; Lifestyle; Prevention; Primary care.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The trial was approved by the medical Ethics Committee of the University Medical Center (UMC) Utrecht (NL61553.041.17) and was registered in the Dutch Trial register (reference: NTR7304). All participants signed informed consent to participate. Consent for publication: All participants in the study signed informed consent for publication. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Design of the Stepwise-HTN study. *BP = blood pressure, BMI = Body Mass Index, EQ-5D = Euro Quality of live on 5dimensions, Eq. 5D-VAS = EQ5D–Visual Analogue Scale, CVD = cardiovascular diseases, BMQ = Beliefs about Medication Questionnaire
Fig. 2
Fig. 2
Achieved participant flow diagram in the STEPWISE study
See this image and copyright information in PMC

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