# Stopping antihypertensive Treatment amOng hypertensive patients in Primary care: The STOP-Trial

J-M Boivin, João Pedro Ferreira, M Lopez-Sublet, K Duarte, Kévin Duarte, Faiez Zannad, Patrick Rossignol, Nicolas Girerd

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J-M Boivin, João Pedro Ferreira, M Lopez-Sublet, K Duarte, Kévin Duarte, et al.. Stopping anti-hypertensive Treatment amOng hypertensive patients in Primary care: The STOP-Trial. European Journal of Preventive Cardiology, 2025, 10.1093/eurjpc/zwaf511. hal-05219742

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# Stopping antihypertensive Treatment amOng hypertensive patients in Primary care: The STOP-Trial

J-M. BOIVIN¹, MD, PhD; J.P. FERREIRA¹,², MD, PhD; M. LOPEZ-SUBLET³, MD; K. DUARTE¹, PhD, MSc; F. ZANNAD¹, MD, PhD; P. ROSSIGNOL¹,⁴, MD, PhD; N. GIRERD¹, MD, PhD.

1/ Université de Lorraine, Centre d'Investigations Cliniques Plurithématique 1433 and Inserm U1116, CHRU Nancy, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France.

2/ Department of Physiology and Cardiothoracic Surgery, Cardiovascular R&D Centre - UnIC@RISE, Faculty of Medicine of the University of Porto, Porto, Portugal; Heart Failure Clinic, Internal Medicine Department, Unidade Local de Saúde de Gaia/Espinho, Gaia, Portugal.

3/ AP-HP, Hôpital Avicenne, Centre d'Excellence Européen en Hypertension Artérielle, Service de Médecine Interne ; INSERM UMR 942 MASCOT, Paris 13-Université Paris Nord, Bobigny ; FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists).

4/ Medical Specialties and Nephrology departments, Princess Grace Hospital, Monaco, Monaco.

Corresponding author: J-M. BOIVIN: jm.boivin@chru-nancy.fr
1 ABSTRACT

2 **Background:** Antihypertensive therapy (AHT) is usually lifelong. The feasibility of
3 discontinuing AHT in selected individuals is insufficiently studied.

4 **Aims:** To assess the feasibility of discontinuing AHT in patients on monotherapy or low-dose
5 dual therapy, and identify factors associated with maintaining normotension without treatment for
6 one year.

7 **Methods:** This prospective, multicenter, non-randomized, open-label study assessed stopping
8 AHT in individuals without self-reported cardiovascular risk factors (other than hypertension) or
9 target organ damage, on monotherapy or low-dose dual AHT. The primary endpoint was
10 maintaining normotension (<135/85 mmHg) for one year (with measurements at 1, 3, 6, 9, and 12
11 months) based on home blood pressure measurements (HBPM). Factors associated with success
12 and failure of maintaining normotension were explored.

13 **Results:** Among 401 screened individuals, 218 (54.4%) were included after confirmation of
14 controlled blood pressure (BP) by HBPM at baseline and their AHT was discontinued within 3
15 days. 203 participants had available BP measurements throughout the follow-up and were
16 analyzed. Their mean age was 58.2 (±10.1) years, and 47.3% were women. Of these 203, 73
17 (36%) maintained BP <135/85 mmHg for one year without AHT while 130 patients (64%)
18 required resumption of their AHT during the follow-up. Baseline HBPM predicted BP values at
19 one year, while office BP or white coat hypertension did not. Patients with systolic HBPM <120
20 mmHg prior to AHT discontinuation had a 60% chance of maintaining normal BP, compared to
21 23% with systolic HBPM ≥120 mmHg. One patient with systolic HBPM >120 mmHg at baseline
22 experienced an ischemic stroke.

23 **Conclusions:** About one-third of individuals on monotherapy or low-dose dual AHT who discontinued treatment maintained controlled BP after one year. Discontinuing AHT may be
1 considered in selected individuals with HBPM below 120 mmHg, provided close BP monitoring

2 is performed, particularly within the first year of AHT withdrawal. Clinicaltrials.gov registration

3 number: NCT02268071

4 Keywords: Hypertension, antihypertensive therapy discontinuation, blood pressure control, home

5 blood pressure measurement

6

7

8 **Lay summary**

9 **Overview**

10 The STOP-Trial investigated whether discontinuing antihypertensive therapy (AHT) is feasible

11 for patients who have controlled hypertension and no additional cardiovascular risk factors or

12 target organ damage. The primary goal was to assess if these patients could maintain normal

13 blood pressure without medication for one year.

14

15 **Key Findings**

16 • Approximately one-third of participants successfully maintained normal blood pressure for one year after stopping their antihypertensive medication.

17 • Patients with a baseline home blood pressure measurement (HBPM) below 120 mmHg had a significantly higher likelihood of maintaining normal blood pressure without treatment. Specifically, these patients had a 60% chance of maintaining normotension compared to only 23% for those with higher baseline systolic HBPM.

22
# 1 Introduction

2 Hypertension is a major cardiovascular risk factor worldwide.¹,² Most people living with 3 hypertension have uncontrolled blood pressure (BP).¹ Still, the proportion of controlled BP has 4 been reported to be approximately 40% among hypertensive people in high-income western 5 countries.¹

6 While the recommendations insist on the importance of early detection and treatment, they 7 do not sufficiently emphasize the need to repeat BP measurements: a first office visit (with 8 measurements with 1 min intervals) with at least 1 additional office visit (e.g. within 4 weeks)³, 9 and, confirm the diagnosis whenever possible with home blood pressure measurements (HBPM) 10 and/or 24H Ambulatory Blood Pressure Measurement (ABPM)⁴, to exclude “white coat” 11 hypertension (WCHT), which does more often than not require treatment according to the current 12 recommendations.⁵,⁶ Moreover, BP may be controlled with life-style and dietary changes. 13 Hypertension has generally been considered an incurable illness requiring life-long 14 pharmacological and dietary therapy. Still, in most cases, once a person is labelled as 15 “hypertensive” and is started on anti-hypertensive drug therapy (AHT), this diagnosis is most likely 16 never challenged, even if the patient has controlled or even low BP on monotherapy or low-dose 17 dual AHT, leading indefinitely continuing AHT.

18 Moreover, although guidelines recommend regular HBPM during follow-up, it is rarely 19 repeated in routine clinical practice,⁷ as attending physicians often rely primarily on office BP 20 measurements, including for patients with WCH.

21 In this case, the BP may appear normal with office measurement, whereas it is much lower 22 when measured in HBPM.⁷
We hypothesize that discontinuation of AHT may be attempted among individuals without cardiovascular or neurovascular disease who started AHT without adequate confirmation of hypertension diagnosis and/or without HBPM monitoring during the follow-up.

To identify patients diagnosed with hypertension who may not require continuation of AHT, we designed a study aimed to discontinue AHT in individuals without associated cardiovascular or neurovascular disease or target organ damage, treated with monotherapy or low-dose dual AHT. While not all patients on monotherapy fall into this category, a significant proportion do, particularly among those with early-stage hypertension. This target population constitute a substantial share of hypertensive patients as 60% of hypertensive patients are treated with a monotherapy in France⁸ and other countries⁹⁻¹¹, despite European Society of Hypertension (ESH) guidelines recommending to initiate the treatment with a combination therapy⁵.

12

# 13 METHODS

## 14 Trial design

STOP-Trial is a prospective, multicenter, non-randomized, open-label study assessing the feasibility of maintaining normotension without AHT for one year after discontinuation of antihypertensive monotherapy or low-dose dual therapy.

The trial was sponsored by a grant from the French Ministry of Health (*Programme hospitalier de Recherche Clinique Inter-régional*). This study follows the principles of the Declaration of Helsinki and is in accordance with Good Clinical Practices and French regulations.

It was approved by the French Health Authorities (*Agence nationale de la sécurité du médicament et des produits de santé, ANSM*) and the appropriate Ethics Committee (*Comité de Protection des Personnes, CPP Est III*).

24
# 1 Patient population

2 From March 2015 to October 2019, patients were recruited and screened for eligibility. All
3 eligible patients were required to be older than 18 years of age and reported to have grade 1
4 hypertension at the time of diagnosis. They were treated with AHT monotherapy or low-dose dual
5 therapy. This initial treatment was prescribed by general practitioners based on their clinical
6 judgment. Patients with history of target organ damage or cardiovascular or neurovascular disease
7 were excluded. A full list of inclusion and exclusion criteria is provided in the *Supplementary Appendix 1*.

9 The trial intended to recruit patients both through general practitioners (GPs) and via public
10 outreach.

11 All the patients provided written informed consent.

12

13 Trial strategy

14 The main objective of this study was to identify factors associated with maintaining
15 normotension one year after discontinuation of antihypertensive treatment in patients defined as
16 hypertensive and from "real life." These patients were not hypertensive according to SFC criteria
17 (based on clinical and ambulatory BP measurements) but were defined as hypertensive by their
18 own GP.

19 We hypothesize that, in real life, a large number of patients had white-coat hypertension,
20 which was undiagnosed by the GP who had not taken any measurements outside the office. Other
21 patients were not hypertensive but were diagnosed as hypertensive by the attending physician,
22 despite the absence of repeat measurements to confirm the persistence of hypertension. In fact,
23 some doctors initiate treatment without repeating BP measurements or verifying that these
measurements remain high after several sequences of measurements spread over multiple consultations, as required by the recommendations.

The strategy was to identify those patients treated with monotherapy who are most likely to be able to manage without antihypertensive treatment. These patients are likely to be either non-hypertensive or have white-coat hypertension.

## Trial procedures

At the pre-screening visit, we searched for target organ damage at inclusion, which was an exclusion criterion based on the following evaluations: albuminuria and left ventricular hypertrophy on ECG or echocardiography. Patient eligibility was first assessed through a medical interview (the absence of a risk factor was based on the patient's declaration), clinical examination, and ECG (if not performed or available in the previous year). If left ventricular hypertrophy was present on ECG (as assessed by Sokolov and Cornell scores), an echocardiogram was performed. Additionally, proteinuria was assessed using urine strips, if these tests had not been performed or documented in the previous year.

Eligible patients at the end of this visit were provided with an automatic blood pressure monitor for HBPM. As this trial is a pragmatic study reflecting routine care management, HBPM was used rather than ABPM to confirm BP values. The HBPM was carried out in accordance with the ESH/ESC instructions. Patients were instructed on how to perform HBPM during the first visit. Home BP measurements were recorded by the patients themselves in a dedicated logbook, which was then transcribed into an Excel spreadsheet by two independent operators using double data entry. The average HBPM was calculated by taking the mean of the morning and end-of-day measurements, excluding those taken on the first day.
1

As the STOP-Trial is a pragmatic study reflecting routine care management, we chose to use HBPM rather than ABPM to confirm BP values. This choice ensured the feasibility and tolerability of the trial, as HBPM can be repeated six times in one year in patients maintaining normal BP, which would have been difficult for volunteers to accept if we had chosen ABPM. Quality of life was assessed using the SF36 Scale (Appendix 2).

We ensured that there was no target organ damage by checking for the absence of albumin in the urine, the absence of electrical left ventricular hypertrophy (LVH), and, where appropriate, conducting an ultrasound, along with a normal clinical examination. We inquired about the patients' cardiovascular history (stroke, transient ischemic attack, myocardial infarction, peripheral artery disease, etc.). None of them had a history of cardiovascular or cerebrovascular disease, which was a criterion for non-inclusion. We did not measure cholesterol or blood sugar levels, as these were not criteria for non-inclusion. We only interviewed patients.

14

At baseline (visit 1), patients were included if their HBPM measurements confirmed controlled hypertension (mean HBPM<135/85 mmHg, achieved for 7 consecutive days in the 10 days prior to visit 1). Following study inclusion, antihypertensive treatment was reduced (half dose) and then discontinued over a period of 3 days.

Patients were subsequently followed up at 1, 3, 6, 9, and 12 months. The investigator reinstated antihypertensive treatment if 1) mean HBPM was >135/85 mmHg over two consecutive visits or 2) mean HBPM was >155/95 mmHg at one visit. Office blood pressure levels during the follow-up visits were not considered in the decision to reinitiate treatment to avoid acting on white coat hypertension, in line with hypertension guidelines.
At recruitment, baseline data were collected by physicians using a standardized questionnaire. At follow-up visits, trained staff measured office blood pressure and recorded adverse events and HBPM readings. Blood pressure was measured three times at 1-minute intervals using automatic monitors dedicated to the study (Microlife BPA200 humeral cuff blood pressure monitor) validated on StrideBP, for all participants in order to standardize the measurements. after patients rested for 5 minutes. Normal blood pressure was defined as an average of less than 135/85 mmHg based on 7 days of HBPM readings.

## Trial outcomes

The primary outcome was the rate of normotensive patients for 1 year (HBPM <135/85 mmHg) after treatment discontinuation, based on data collected at 1, 3-, 6-, 9-, and 12-months follow-up.

Secondary outcomes included the rate of normotensive patients for 1, 3, 6, and 9 months, and changes in the quality-of-life scale (SF36).

## Sample size

To estimate the association of six factors with normotension at 1 year, a sample of at least 60 patients who maintained normalized blood pressure (BP <135/85 mmHg) at 1 year was required. These candidate factors included white coat hypertension, therapeutic class of antihypertensive drugs, use of HBPM or ABPM for diagnosis, BP level at diagnosis, weight loss, associated treatments, gender, and age.

Considering an estimated 20% probability of normotension at 1 year, a 10% rate of non-assessable patients or unjustified resumption of antihypertensive treatment, and 20% of patients with masked hypertension (7-day mean BP ≥135/85 mmHg on HBPM), we initially planned to pre-include 420 patients (i.e., patients who signed informed consent at the first consultation prior
1 to HBPM). The trial was terminated once 60 patients were confirmed to have maintained normal

2 BP without treatment at 1 year.

3 Statistical analysis

4 Characteristics are described as mean with standard deviation (SD) for continuous

5 variables, median with interquartile range (IQR) for data with skewed distributions, and frequency

6 (percentage) for categorical variables.

7 Characteristics were compared between groups (included vs. non-included patients,

8 normotensive vs. hypertensive patients) using t-test or Mann-Whitney test for continuous variables

9 and Fisher's exact test for categorical variables. We also assessed balance of characteristics

10 between groups by calculating absolute standardized mean differences (ASMD).

11 For the primary outcome (maintenance of normotension at 1 year), ROC curves were

12 plotted for mean ABPM SBP and mean APBM DBP and an optimal threshold was determined for

13 each parameter using the "closest to topleft" method, i.e. the threshold that minimizes the criterion

14 (1 - Sensitivity)² + (1 - Specificity)²

15 To identify factors associated with the primary outcome, multivariable logistic regression

16 model was built using a two-step variable selection process: pre-selection of variables with a

17 univariable p-value < 0.20, followed by forward stepwise selection with a threshold of p < 0.05.

18 The robustness of the selected variables, the stability of the multivariable model and its

19 generalizability in predictive performance were assessed using bootstrap resampling approach. The

20 concordance index (c-index) was reported for each ROC curve and multivariable logistic model.

21 In addition to the stepwise logistic regression model, we conducted a sensitivity analysis

22 using penalized logistic regression via the LASSO method. The penalty parameter λ was selected

23 by minimizing the deviance through 5-fold cross-validation repeated 1000 times. The use of 5 folds

24 was intended to ensure a sufficient number of patients from each outcome group in each fold.
1 Model performance was assessed using the area under the ROC, both in resubstitution and through
2 5-fold cross-validation repeated 100 times. The same validation strategy was applied to stepwise
3 logistic regression model to allow for direct comparison.

4 For additional details regarding the statistical analysis, please refer to the Supplemental
5 Material. All analyses were performed using R software version 4.1.2 (R Foundation for Statistical
6 Computing).

8 RESULTS

9 Patient characteristics

10 Of the 401 screened patients, 70 out of 401 (17.5%) participants were recruited by GPs,
11 while the remaining 331 participants (82.5%) were recruited through press advertisements or
12 posters in public places. All participants were confirmed as hypertensive and treated with an
13 antihypertensive drug by their GP. Regardless of recruitment pathway, participants received the
14 same information and were followed by their GP during the study. There was a run-in phase during
15 which patients were seen twice, one month apart, with blood pressure measurements taken each
16 time before final inclusion.

17 Of the 401 patients screened, 183 were excluded. Four were excluded for reasons unrelated
18 to blood pressure (excessive alcohol consumption or a condition requiring continuation of
19 antihypertensive treatment), 61 due to missing HBPM data, and 118 because their HBPM was
20 ≥135/85 mmHg (uncontrolled or masked hypertension). (Figure 1). Consequently, 218 patients
21 were included in the study, and their antihypertensive treatment was stopped. Fifteen subjects were
22 excluded from the primary outcome analysis due to a missed one-year visit (n=14) or missing
23 HBPM data at one year (n=1). Thus, 203 subjects were included in the primary outcome analysis
24 at one year.
The descriptives of included and ruled-out patients are presented in Table 1. Overall, most patients (n=347, 87%) were treated with monotherapy. All the patients were of normal weight or overweight but not obese. Patients reported no associated risk factors at the time of inclusion. However, follow-up assessments identified a small proportion with undiagnosed or previously unreported conditions, including diabetes, dyslipidemia, or obstructive sleep apnea.

Patients reported that before the inclusion, the diagnosis of hypertension had been often confirmed after at least 3 blood pressure measurements at 3 different consultations in 55% of patients and 72% of patients reported having either HBPM and/or ABPM (respectively 40% and 55%). Despite this, white coat hypertension was frequent in this population. Indeed, 85/203 (42%) patients had BP ≥ 140/90 mmHg on clinical measurement at the inclusion visit but <135/85 mmHg on self-measurement, indicating white coat hypertension. Interestingly, only 38% of volunteers who maintained normotension at one year were correctly diagnosed initially by their GP as hypertensive, using repeated blood pressure measurements and out-of-office methods (HBPM and/or ABPM).

## Primary outcome

Among 203 included patients in whom the primary outcome could be measured, 73 (36%) exhibited BP <135/85 mmHg in HBPM at all follow-up visits without AHT, thus completing the primary outcome (Table 2), while 130 patients (64%) required resumption of their antihypertensive treatment during the year of follow-up. The apparent decrease in uncontrolled patients at 9 months is explained by the composite definition of treatment resumption, which incorporated previous BP values and self-reported treatment restart, not only the 9-month BP measurement.
# 1 Secondary outcome

Most patients developed uncontrolled BP within 3 months after stopping AHT. At 3 months, only 86 patients remained normotensive without AHT, a number further reduced to 73 at 12 months (Table 2).

# 5 Association of variables with the primary outcome

When comparing patients who met or did not met the primary outcome (Table 3, supp Table 1), office blood pressure was not significantly associated with the outcome. In contrast, HBPM variables were the only variables with a p<0.01. The only other variable significantly associated with the primary outcome was ARBs. Notably, the average duration between starting antihypertensive treatment and the inclusion visit did not differ across groups: 5 years (range: 2.1-11.0) for patients who remained normotensive, compared to 5.4 years (range: 2.0-10.0) for those who remained normotensive at one year. There was no significant change in weight in the group that maintained normotension at 1 year. Likewise, there was no significant change in weight in the groups of patients who resumed treatment at 3 months, 6 months, 9 months, or 1 year.

Interestingly, In the STOP TRIAL, 36% of patients were taking antihypertensive medications at doses lower than the standard dosage, and in some cases, at extremely low doses.

# 19 Determination of baseline HBPM cut-offs to predict the primary outcome

Mean HBPM SBP and mean HBPM DBP were considered as continuous variables in model 1 and as binary variables dichotomized according to thresholds in other models (clinical thresholds and/or optimal thresholds determined from ROC curve as shown in Figure 2).
# 1 Models predicting the primary outcome

Multivariable models included only 3 significant variables, namely ARB treatment and
HBPM measurements at baseline (Table 4). When repeating the variable selection process using a
bootstrap resampling approach, these three variables were the only ones retained in more than 50%
of the samples, supporting the stability of the identified predictors (Supplemental Figure 1). In
model #1 (continuous BP variables), both higher average SBP and DBP on HBPM prior to AHD
stop were associated with lower rates of one-year primary outcome. In model #2, considering the
relevant clinical threshold, SBP>120 and DBP>80 mmHg at HBPM at baseline were both
associated with 3 to 4 times lower chances of meeting the primary outcome. Model #3 considered
the data-driven best cut-offs of SBP and DBP on HBPM prior to AHD stop to predict the primary
outcome: SBP=122.5mmHg and DBP=74.5mmHg, respectively, with a 65% chance of normal
one-year BP without treatment.

All pairwise interaction terms between variables included in the model were tested
individually in the presence of the main effects and found to be non-significant (p > 0.15 for all).

The models demonstrated good stability and accuracy in predicting the probability of
successful antihypertensive treatment discontinuation, with a C-index of approximately 0.77 across
all models Model #1 demonstrated good generalizability, with an OOB c-index > 0.75 slightly
lower to that obtained the model fitted on the full dataset (Supplemental Table 2).

19

# 20 Penalized Regression Results

The LASSO model selected four variables: mean systolic HBPM at inclusion, mean
diastolic HBPM at inclusion, ARB treatment, and antihypertensive therapy type (monotherapy vs.
bitherapy). The corresponding coefficients and performance metrics are shown in Supplemental
Table 3.
1 The area under ROC for the LASSO model was 0.776 in resubstitution and 0.741 in 5-fold
2 cross-validation repeated 100 times. For comparison, the stepwise logistic regression model
3 (Model 1) had an area under ROC of 0.773 in resubstitution and 0.759 in the same cross-validation
4 framework.

5

6 Safety

7 No dizziness, headache, or discomfort were observed in the included patients. No
8 retreatment was necessary for clinical reasons other than a rise in blood pressure, except in one
9 patient who experienced a serious adverse event (ischemic stroke). This patient had a HBPM
10 >120/80 mmHg at baseline.

11

12

13 DISCUSSION

14 The STOP-Trial results indicate that 36% of controlled hypertensive patients without target
15 organ damage or a history of cardiovascular disease treated with monotherapy or dual low-dose
16 AHT maintained normotension 12 months after discontinuing therapy, while 64% needed to take
17 over AHT during the year of follow-up.

18 In 1988, Fletcher reviewed the literature on the effect of discontinuing antihypertensive
19 treatment in treated hypertensive patients. Depending on the study, 15-50% remained normotensive
20 after stopping treatment.12 The first real longitudinal interventional study on discontinuing
21 antihypertensive treatment under usual care conditions dates back to 1999. Conducted by 18
22 English general practitioners on 196 patients, this study defined hypertension control as BP<
23 160/90mmHg both at inclusion and after discontinuation of antihypertensive treatment. Blood
24 Pressure was measured exclusively in office, introducing potential bias due to variability of clinical
measurements. Additionally, patients with white-coat hypertension were not identified, as no out-of-office measurements were performed¹³.

In the present study, a baseline HBPM <120 mmHg was an independent predictor of sustained BP control at 1 year. Specifically, patients with a systolic HBPM <120 mmHg prior to AHT discontinuation had a 60% chance of maintaining normal BP without treatment, compared to 23% for those with a systolic HBPM ≥120 mmHg. Still, stopping AHT led to uncontrolled BP in 64% of participants and, among these, one patient had an ischemic stroke. Overall, these findings suggest that discontinuing AHT should only be considered in selected low-risk patients in whom systolic HBPM is below 120 mmHg under single or dual AHT without target organ damage or a history of cardiovascular disease, and in whom frequent BP monitoring is performed; The remainder of individuals should continue AHT for optimal BP controlled.

While discontinuation of antihypertensive drugs has been considered in elderly patients¹⁴, primarily due to potential side effects, few studies have examined younger, lower-risk patients. Our study excludes frail elderly hypertensive patients, for whom there is ongoing controversy regarding the continuation of treatment due to potential negative impacts on cognitive function and overall morbidity and mortality¹⁵⁻¹⁷. Instead, our study focuses on the potential for stopping antihypertensive therapy in low-risk, relatively young patients. Our findings align with the viewpoint of Schmieder et al., published three decades ago, which identified young patients with low blood pressure, successful therapy with one drug only, and minimal or no signs of target organ damage as the best candidates for discontinuation¹⁸. These factors were later confirmed as significant predictors of normotension maintenance without antihypertensive therapy by Nelson et al. in 2003¹⁹. The authors concluded that it is possible to discontinue antihypertensive treatment in uncomplicated patients on monotherapy and willing to comply with hygienic and dietary measures. A systematic review published in 2017 also identified monotherapy, lower blood pressure before
withdrawal, and lower body weight as predictors for successful withdrawal²⁰. The STOP trial provides interventional evidence to test these previous findings in an experimental setting, reinforcing the potential for safely discontinuing antihypertensive therapy in selected low-risk, relatively young patients.

Of note, our recruitment method allowed us to reach a diverse group of participants who were motivated to take part in the study out of personal or societal interest rather than clinical recommendation. This approach may reduce selection bias and enhance the generalizability of our findings to a broader population. It also underscores the importance of community engagement and public awareness in research, suggesting that similar recruitment strategies could be beneficial in future studies aiming to capture a wide array of perspectives and experiences.

The most actionable finding of our study is that patients with a systolic HBPM <120 mmHg had a high probability of maintaining normotension at 12 months without antihypertensive therapy, with none experiencing major adverse events. This threshold closely aligns with the minimum recommended blood pressure targets set with office blood pressure by the ESH 2023 guidelines,²¹ which avoid intentionally lower targets. Our analysis, guided by ROC curve analysis, identified an optimal threshold very close to 120 mmHg, specifically 122 mmHg. This data-driven result reinforces the practicality and safety of using a systolic HBPM threshold of 120 mmHg for and ESC guidelines⁴ considering the discontinuation of antihypertensive therapy in low-risk patients, especially as a drop in SBP below 120mmHg is associated with an increase in cardiovascular events and mortality.²²

Understanding why a significant proportion of patients can successfully stop BP medication is complex. Three main reasons can be suggested.
First, some patients may have recovered from hypertension due to lifestyle changes, such as weight loss and reduced salt consumption between inclusion and final visit. However, our analysis did not find significant differences in weight loss or other lifestyle factors between groups, except for alcohol consumptions which was lower among individuals with normotension at 1 year. Nevertheless, overall alcohol consumption was low and unlikely to explain the observed differences.

Another hypothesis is that some patients may have been started on treatment early, without waiting for the results of the lifestyles changes. Doctors would then have continued to treat patients, especially white-coat hypertensives, without checking blood pressure measurements using HBPM, which is very rarely used in France to monitor hypertensive patients²³,²⁴ as recommended by ESC guidelines ⁴. But the use of HBPM is insufficient also in the other countries²⁵⁻²⁷.

A third possibility is that some patients did not have true hypertension at baseline, due to the inherent variability of blood pressure and the absence of confirmation by ambulatory or home blood pressure monitoring — a situation that remains common in current practice²³. Although a significant number of patients included in the STOP-Trial exhibited white-coat hypertension, the strongest predictor of maintaining normotension at one year was a low baseline systolic self-measured blood pressure (<120 mmHg), rather than the presence of white-coat hypertension. Fluctuations observed in the white-coat effect are mainly caused by office blood pressure variability²⁸ and patients with white-coat hypertension have higher blood pressure variability compared to normotensive individuals²⁹. Visit-to-visit variability is a recognized limitation in all hypertension studies; interestingly, greater visit-to-visit systolic blood pressure variability is associated with an increased risk of cardiovascular disease and mortality, as shown in the ALLHAT study³⁰. Systolic blood pressure variability has also been identified as a strong independent predictor of stroke, and residual variability among treated hypertensive patients remains associated
1 with a higher risk of vascular events³¹. Notably, blood pressure variability is significantly lower
2 when assessed by home blood pressure monitoring³², although the mechanisms underlying this
3 reduced variability are not fully understood. In our study, hypertension was diagnosed using
4 ambulatory or home blood pressure monitoring in approximately two-thirds of patients, with no
5 significant difference between those who remained normotensive and those who did not, rendering
6 this third hypothesis less likely.
7

8 Our results raise questions about the proportion of truly controlled hypertensive patients in
9 Western countries. This raises the issue of whether some patients diagnosed with hypertension and
10 considered controlled are truly hypertensive or were either incorrectly diagnosed or had resolving
11 hypertension. The proportion of truly controlled hypertensive patients (those who remain
12 hypertensive but have controlled BP due to their medication) would be even lower if we consider
13 that a sizeable portion (36% in our study) does not actually need treatment to maintain BP under
14 the threshold.
15

16 A total of 33 patients resumed antihypertensive treatment before the end of the study,
17 including some on the advice of their primary care physician and others on their own initiative.
18 These patients were often monitoring their blood pressure more frequently and may have perceived
19 a benefit from being on treatment. The factors associated with such self-initiated resumption of
20 therapy warrant further investigation, possibly through studies incorporating a sociological or
21 behavioral perspective.
22
23
24
# 1 Clinical Perspectives

Acknowledging the burden of lifelong adherence and the associated issue of non-adherence, our data suggest that temporary discontinuation could be a reasonable option for selected patients without established cardiovascular disease, with readiness to resume antihypertensive therapy if needed. We hypothesize that this approach might help convince patients of the necessity of continued treatment when it is genuinely required. Therefore, our results suggest that a sizeable proportion of controlled hypertensive patients might not need ongoing treatment. Notably, more than 50%³³ of hypertensive patients in Western countries are treated with monotherapy, supporting the broad applicability of our results to routine practice.

10

# 11 Limitations

Despite our team's high level of engagement in the trial, some patients did not have BP measurements at 12 months, reducing the number of analyzed patients from 218 to 203. This could introduce selection bias. HBPM was preferred over ABPM for reasons of feasibility and applicability to routine clinical practice, although ABPM would have provided a more precise assessment of BP control. Additionally, trial recruitment was primarily through GP referrals, and the referred patients might not represent the broader target population. The profile of GPs referring to clinical studies may be related to intrinsic differences in their treating populations, potentially leading to further selection bias. We did not measure the amount of salt ingested, we did not carry out a dietary survey, we did not assess stress, sleep quality, and we did not assess the quality of the sleep we received. We did not assess physical activity.

Another limitation of the STOP-Trial maybe the absence of a control group continuing antihypertensive treatment. This omission makes it challenging to precisely determine the effects of discontinuing medication. While this does not impact our primary objective of identifying
factors associated with maintaining normotension without treatment, it is a limitation for assessing
the safety of stopping treatment. Hypertensive patients have a residual risk even under treatment,
and understanding these clinical effects would benefit from a control group. Additionally, having
a control group would have helped mitigate the risk of seasonal variations influencing our results.

However, given that the study was conducted over a long period with inclusions spread over several
years, we can exclude the influence of seasonal blood pressure variations.

The patients defined as hypertensive in this study reflect real life clinical practice. They
were diagnosed as hypertensive by their GP, but may often not meet the ESC definition criteria. A
sizeable proportion likely had white-coat hypertension, while others may have been misdiagnosed
and were in fact normotensive

We identified ARBs as being associated with BP maintenance at 12 months after stopping
antihypertensive therapy. The rationale behind this association is uncertain and may require more
targeted analysis on a larger scale. However, this result can be compared with the results of the
TROPHY study ³⁴ which shows that treatment of prehypertension with an ARB (candesartan)
appeared to be reduced the risk of incident hypertension during the study period among
prehypertensive patients. It is possible, as in the TROPHY study, that treatment with ARBs may
slow the progression to hypertension in patients with prehypertension

This study was limited to a short follow-up period, and it would have been highly
informative to assess long-term outcomes in this patient population. Further studies are needed to
determine whether discontinuing AHT can be sustained in the long term.

The patients included in the STOP-Trial were overall compliant to treatment based on self-
declared evaluation (Girerd questionnaire). However, it cannot be ruled out that some patients were
non-adherent despite claiming compliance. This reflects real-life scenarios, where routine drug
measurements in urine to assess compliance are not feasible. However, we cannot exclude the
possibility that some patients who maintained normal BP at one year were actually non-compliant.

Cholesterol and blood glucose levels were not systematically measured at the time of
inclusion. Although participants reported, via the baseline questionnaire, having no history of
hypercholesterolemia or diabetes and not taking any related medications, the possibility of
undiagnosed cardiometabolic conditions cannot be entirely excluded. This limitation reflects a
common challenge in routine clinical practice, particularly in pragmatic trials. Notably, during the
course of the study, 21 participants reported having either treated or untreated dyslipidemia,
including 14 who were taking a statin, which underscores the inherent limitations of relying on
self-reported data. These findings highlight the trade-off between real-world feasibility and data
completeness in pragmatic study designs.

SCORE2 was not calculated due to the absence of key variables such as lipid profile,
creatinine, or albuminuria. However, based on the baseline characteristics of the study population
and the absence of secondary prevention or target organ damage, the overall cardiovascular risk
appears to have been low.

Of note, only ECG was used to rule out LVH, acknowledging its limited sensitivity.
However, it remains the first-line tool recommended in primary care settings for LVH screening,
particularly in resource-limited contexts. Given the general practitioner-centered nature of the
study, more advanced phenotyping—such as echocardiographic assessment of cardiac structure
and function or vascular imaging—was not performed. Echocardiography is indeed more sensitive
and is often recommended as a second-line examination when ECG is normal but clinical suspicion
remains. However, this was beyond the pragmatic scope and budgetary feasibility of our primary
care-based protocol. Detailed hemodynamic parameters such as cardiac output, stroke volume, and
total peripheral resistance were not systematically collected, which may have limited deeper
mechanistic insights into predictors of sustained normotension after treatment withdrawal. These
evaluations, although relevant in specialized care, are not routinely available in real-life primary
care practice.

The results of our study reflect real-world practice, where diagnostic procedures may be
incomplete. Importantly, these results would likely differ if all patients had undergone a full risk-
stratification process including repeated office visits, home or ambulatory BP monitoring,
SCORE2 calculation, and systematic assessment of hypertensive-mediated organ damage using
laboratory and imaging tools.

One of the limitations of our study is the absence of data on family history of hypertension, which can be a significant factor related to the development and management of hypertension.

Finally, the use of a fixed 1-year timepoint for assessing normotension, while facilitating
interpretability, may lead to a loss of temporal information and reduced statistical power. Time-to-
event approaches, which could better account for censoring, treatment changes, and adherence
variability, were not applied here.

## Conclusions

In the STOP trial, one-third of individuals on monotherapy or low-dose dual AHT who discontinued treatment maintained controlled blood pressure after one year, the remainder two-thirds did not. Discontinuing AHT was more likely to be successful among people with a baseline HBPM below 120 mmHg, providing frequent BP monitoring is performed and AHT re-introduced whenever required. This suggests that temporary discontinuation of AHT could be a viable option for a sizeable proportion of the over one billion hypertensive patients worldwide, particularly those who are low-risk and have well-controlled blood pressure. Further research is needed to confirm
1 these findings over a longer period and to better understand the long-term feasibility and safety of

2 AHT discontinuation.

3

4 **Data availability statement**

5 Data will be available upon reasonable request to the Principal Investigator and must be approved

6 by the sponsor.

7

8 **Authors' contributions**

9 JMB participated in the design of the study, is principal investigator of the study, and contributed to the drafting of the manuscript. NG participated in the design of the study (primary outcome measurement-statistical analysis) and contributed to the revising of the manuscript. PR in the design of the study and contributed to the revising of the manuscript. XL participated in the design of the study (randomization and data management). ZL participated in the design of the study (statistical analysis). LM participated in the data management of the study. JPF co-drafted the first version of the manuscript and its subsequent revisions, and provided critical input for result interpretation and analysis. All authors read and approved the final manuscript.

17 All authors have read and approved the final submitted version of this manuscript.

18

19 **Abbreviations :**

20 HBPM: Home Blood Pressure Measurement

21 GCP: Good Clinical Practices

22 CIC-P: Plurithematic Clinical Investigation Center

23 CPP: Committee for the Protection of Persons

24 CRF: Case Report Form
1 ABPM: Ambulatory Blood Pressure Measurement

2 GP: General Practitioner / General Medicine

3 BP: Blood Pressure

4 SBP: Systolic Blood Pressure

5 DBP: Diastolic Blood Pressure

6

7 Acknowledgements

8 We would like to thank the patients who agreed to participate in the study and the investigating

9 physicians who helped us to include the first volunteer patients.

10

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2 10.1093/ajh/hpx221

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9 10.1056/NEJMoa060838

10
1 **Figure 1: Flow chart of the study**

2

<figure><img src="image_2.png" /></figure>

3

4

5
Figure 2: Accuracy of home blood pressure measurements in predicting maintenance of normotension at one year.

Receiver operating characteristic (ROC) curves for mean systolic (SBP, red) and diastolic (DBP, blue) home blood pressure measurements (HBPM) at inclusion in predicting maintenance of normotension at one year. The optimal cut-off values identified were 122.5 mmHg for SBP and 74.5 mmHg for DBP. The corresponding C-index values (95% confidence intervals) were 0.706 (0.631–0.781) for SBP and 0.740 (0.671–0.809) for DBP. The diagonal reference line represents a non-informative classifier. For mean systolic HBPM, specificity/sensitivity was equal to 0.654/0.685 for optimal threshold of 122.5 mmHg, and respectively 0.738/0.603 for clinical threshold of 120 mmHg. For mean diastolic HBPM, specificity/sensitivity was equal to 0.746/0.671 for optimal threshold of 74.5 mmHg, and respectively 0.400/0.904 for clinical threshold of 80 mmHg.
<figure><img src="image_3.png" /></figure>

1
2
3
<table><caption>1 Table 1: Descriptives at screening of included and ruled-our patients</caption><thead><tr><th>Variable</th><th>Excluded patients for<br>analysis of primary<br>outcome (n=198)</th><th>Included for analysis<br>of primary outcome<br>(n=203)</th><th>p-value*</th><th>ASMD</th></tr></thead><tbody><tr><td><strong>Demographics</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Age</td><td>58.4 ± 10.6 [n=197]</td><td>58.1 ± 9.6</td><td>0.83</td><td>0.022</td></tr><tr><td>Gender</td><td></td><td></td><td>0.0009</td><td>0.341</td></tr><tr><td>Male</td><td>121 (61%)</td><td>90 (44%)</td><td></td><td></td></tr><tr><td>Female</td><td>77 (39%)</td><td>113 (56%)</td><td></td><td></td></tr><tr><td><strong>Clinical examination</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>BMI (kg/m²)</td><td>27.8 ± 4.3 [n=190]</td><td>26.5 ± 4.5</td><td>0.004</td><td>0.290</td></tr><tr><td><strong>Office BP measurement (inclusion visit)</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>SBP (mmHg)</td><td>144.0 ± 15.7 [n=150]</td><td>134.4 ± 12.8</td><td>&lt;0.0001</td><td>0.675</td></tr><tr><td>DBP (mmHg)</td><td>88.5 ± 9.1 [n=150]</td><td>82.6 ± 7.5</td><td>&lt;0.0001</td><td>0.703</td></tr><tr><td><strong>Hypertension diagnosis</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Confirmed by 3 measures at 3 consultations</td><td>81/152 (53%)</td><td>112/202 (55%)</td><td>0.75</td><td>0.043</td></tr><tr><td>HBP performed</td><td>56/152 (37%)</td><td>86/201 (43%)</td><td>0.27</td><td>0.122</td></tr><tr><td>ABPM performed</td><td>86/151 (57%)</td><td>106/200 (53%)</td><td>0.52</td><td>0.080</td></tr><tr><td>HBPM or ABPM performed</td><td>107/152 (70%)</td><td>146/201 (73%)</td><td>0.72</td><td>0.050</td></tr><tr><td><strong>Treatments</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>ACE inhibitor</td><td>54/181 (30%)</td><td>49 (24%)</td><td>0.25</td><td>0.129</td></tr><tr><td>ARB</td><td>73/181 (40%)</td><td>101 (50%)</td><td>0.066</td><td>0.190</td></tr><tr><td>Thiazide diuretic</td><td>15/181 (8%)</td><td>20 (10%)</td><td>0.72</td><td>0.055</td></tr><tr><td>Béta-blocker</td><td>26/181 (14%)</td><td>31 (15%)</td><td>0.89</td><td>0.026</td></tr><tr><td>Other treatment</td><td>27/181 (15%)</td><td>15 (7%)</td><td>0.022</td><td>0.241</td></tr><tr><td><strong>Target organ damage</strong></td><td>39/185 (21%)</td><td>0 (0%)</td><td>&lt;0.0001</td><td>0.731</td></tr></tbody></table>

2

3 ASMD: absolute standardized mean difference.

4 Values are mean ± SD or median (IQR) for continuous variables and frequency (percentage) for categorical variables.
1 *p-value from t-test or Mann-Whitney test for continuous variables, and chi-square test or Fisher's exact test for categorical variables.

<table><caption>Table 2: Maintenance of normotension at each timepoints in the 203 patients with available primary endpoint</caption><tbody><tr><th colspan="2">Maintenance of normotension at 3 months</th></tr><tr><td>No</td><td>118 (58 %)</td></tr><tr><td>HBPM &gt;= 155/95 mmHg at a previous visit</td><td>2 (1 %)</td></tr><tr><td>AHT resumption before 3 months</td><td>28 (14 %)</td></tr><tr><td>HBPM &gt;= 135/85 mmHg at 3 months</td><td>88 (43 %)</td></tr><tr><td>Yes</td><td>81 (40 %)</td></tr><tr><td>Missing data</td><td>4 (2 %)</td></tr><tr><th colspan="2">Maintenance of normotension at 6 months</th></tr><tr><td>No</td><td>121 (60 %)</td></tr><tr><td>HBPM &gt;= 155/95 mmHg at a previous visit</td><td>7 (3 %)</td></tr><tr><td>HBPM &gt;= 135/85 mmHg during 2 previous consecutive visits</td><td>60 (30 %)</td></tr><tr><td>AHT resumption before 6 months</td><td>30 (15 %)</td></tr><tr><td>HBPM &gt;= 135/85 mmHg at 6 months</td><td>24 (12 %)</td></tr><tr><td>Yes</td><td>82 (40 %)</td></tr><tr><td>Missing data</td><td>0 (0 %)</td></tr><tr><th colspan="2">Maintenance of normotension at 9 months</th></tr><tr><td>No</td><td>133 (66 %)</td></tr><tr><td>HBPM &gt;= 155/95 mmHg at a previous visit</td><td>7 (3 %)</td></tr><tr><td>HBPM &gt;= 135/85 mmHg during 2 previous consecutive visits</td><td>75 (37 %)</td></tr><tr><td>AHT resumption before 9 months</td><td>31 (15 %)</td></tr><tr><td>HBPM &gt;= 135/85 mmHg at 9 months</td><td>20 (10 %)</td></tr><tr><td>Yes</td><td>69 (34 %)</td></tr><tr><td>Missing data</td><td>1 (0 %)</td></tr><tr><th colspan="2">Maintenance of normotension at 1 year</th></tr><tr><td>No</td><td>130 (64 %)</td></tr><tr><td>HBPM &gt;= 155/95 mmHg at a previous visit</td><td>7 (3 %)</td></tr></tbody></table>
<table><tr><td>HBPM &gt;= 135/85 mmHg during 2 previous consecutive visits</td><td>79 (39 %)</td></tr><tr><td>AHT resumption before 1 year</td><td>33 (16 %)</td></tr><tr><td>HBPM &gt;= 135/85 mmHg at 1 year</td><td>11 (5 %)</td></tr><tr><td>Yes</td><td>73 (36 %)</td></tr></table>

1

<table><caption>2 Table 3: Comparison of characteristics according to the primary outcome</caption><thead><tr><th>Variable</th><th>Hypertensive at 1 year (n=130)</th><th>Normotensive at 1 year (n=73)</th><th>p-value*</th></tr></thead><tbody><tr><td><strong>Demographic</strong></td><td></td><td></td><td></td></tr><tr><td>Age (years)</td><td>58.3 ± 10.0</td><td>57.8 ± 9.0</td><td>0.68</td></tr><tr><td>Male</td><td>62 (48%)</td><td>28 (38%)</td><td>0.24</td></tr><tr><td><strong>Modalities of hypertension initial diagnosis</strong></td><td></td><td></td><td></td></tr><tr><td>Confirmed by 3 measures at 3 consultations</td><td>72/129 (56%)</td><td>40 (55%)</td><td>1.00</td></tr><tr><td>Highest Office SBP (mmHg) at the HT initial diagnosis</td><td>160 (150 - 180) [n=113]</td><td>160 (150 - 170) [n=64]</td><td>0.40</td></tr><tr><td>Highest Office DBP (mmHg) at the HT initial diagnosis</td><td>95 (90 - 100) [n=69]</td><td>90 (90 - 100) [n=40]</td><td>0.12</td></tr><tr><td>HBPM performed</td><td>55/128 (43%)</td><td>31 (42%)</td><td>1.00</td></tr><tr><td>ABPM performed</td><td>72/127 (57%)</td><td>34 (47%)</td><td>0.19</td></tr><tr><td>HBPM or ABPM performed</td><td>97/128 (76%)</td><td>49 (67%)</td><td>0.19</td></tr><tr><td>Age at initiation of AHT</td><td>51.1 ± 10.6 [n=128]</td><td>50.4 ± 10.6</td><td>0.65</td></tr><tr><td><strong>Anti-hypertensive treatments</strong></td><td></td><td></td><td></td></tr><tr><td>ACEI</td><td>31 (24%)</td><td>18 (25%)</td><td>1.00</td></tr><tr><td>ARB</td><td>72 (55%)</td><td>29 (40%)</td><td>0.041</td></tr><tr><td>Spironolactone</td><td>4 (3%)</td><td>2 (3%)</td><td>1.00</td></tr><tr><td>Loop diuretic</td><td>0 (0%)</td><td>0 (0%)</td><td>1.00</td></tr><tr><td>Thiazide diuretic</td><td>14 (11%)</td><td>6 (8%)</td><td>0.63</td></tr><tr><td>BB</td><td>17 (13%)</td><td>14 (19%)</td><td>0.31</td></tr><tr><td>BB/alpha-1 blocker</td><td>0 (0%)</td><td>0 (0%)</td><td>1.00</td></tr><tr><td>Alpha-1 blocker</td><td>0 (0%)</td><td>0 (0%)</td><td>1.00</td></tr><tr><td>Centrally acting agent</td><td>0 (0%)</td><td>1 (1%)</td><td>0.36</td></tr><tr><td>CCB-dihydropiridine</td><td>4 (3%)</td><td>5 (7%)</td><td>0.29</td></tr><tr><td>Other CCB</td><td>1 (1%)</td><td>1 (1%)</td><td>1.00</td></tr><tr><td>AHT modalities</td><td></td><td></td><td>0.18</td></tr><tr><td>Monotherapy</td><td>117 (90%)</td><td>70 (96%)</td><td></td></tr><tr><td>Bitherapy</td><td>13 (10%)</td><td>3 (4%)</td><td></td></tr><tr><td>Girerd Observance Score (3 categories)</td><td></td><td></td><td>0.60</td></tr><tr><td>Good adherence</td><td>53 (41%)</td><td>29 (40%)</td><td></td></tr><tr><td>Minimal adherence problems</td><td>76 (58%)</td><td>42 (58%)</td><td></td></tr><tr><td>Poor adherence</td><td>1 (1%)</td><td>2 (3%)</td><td></td></tr><tr><td><strong>Characteristics at inclusion</strong></td><td></td><td></td><td></td></tr><tr><td>Smoking status</td><td>[n=129]</td><td></td><td>0.49</td></tr><tr><td>Non-smoker</td><td>78 (60%)</td><td>50 (68%)</td><td></td></tr><tr><td>Current smoker</td><td>7 (5%)</td><td>2 (3%)</td><td></td></tr><tr><td>Former smoker</td><td>44 (34%)</td><td>21 (29%)</td><td></td></tr><tr><td>Weekly alcohol consumption (no. of drinks)</td><td>2 (0 - 5)</td><td>1 (0 - 4)</td><td>0.043</td></tr><tr><td>Weekly consumption of coffee or tea ( no. of cups)</td><td>14 (7 - 21)</td><td>14 (7 - 21)</td><td>0.33</td></tr><tr><td>Adding salt at the table</td><td>20 (15%)</td><td>8 (11%)</td><td>0.53</td></tr><tr><td>Physical activity</td><td>[n=129]</td><td></td><td>0.37</td></tr><tr><td>None</td><td>24 (19%)</td><td>16 (22%)</td><td></td></tr><tr><td>Less than 3 hours of moderate physical activity per week</td><td>66 (51%)</td><td>30 (41%)</td><td></td></tr></tbody></table>
<table><thead><tr><th>Variable</th><th>Hypertensive at 1 year (n=130)</th><th>Normotensive at 1 year (n=73)</th><th>p-value*</th></tr></thead><tbody><tr><td>More than 3 hours of moderate physical activity per week</td><td>39 (30%)</td><td>27 (37%)</td><td></td></tr><tr><td><strong>Anthropometric variables</strong></td><td></td><td></td><td></td></tr><tr><td>BMI (kg/m²) at inclusion</td><td>27.0 ± 5.3 [n=128]</td><td>26.0 ± 3.6</td><td>0.12</td></tr><tr><td>Change in weight (kg) between the start of AHT and inclusion in the study</td><td>1.5 ± 6.5 [n=118]</td><td>0.7 ± 6.8 [n=69]</td><td>0.41</td></tr><tr><td>Weight loss &gt;= 4 kg between initiation of AHT and the inclusion in the study</td><td>17/118 (14%)</td><td>13/69 (19%)</td><td>0.42</td></tr><tr><td><strong>Comorbidities</strong></td><td></td><td></td><td></td></tr><tr><td>Obstructive sleep apnea</td><td>2 (2%)</td><td>1 (1%)</td><td>1.00</td></tr><tr><td>Diabetes**</td><td>0 (0%)</td><td>0 (0%)</td><td>1.00</td></tr><tr><td>Dyslipidemia**</td><td>16 (12%)</td><td>5 (7%)</td><td>0.34</td></tr><tr><td><strong>BP at inclusion</strong></td><td></td><td></td><td></td></tr><tr><td><strong>HBPM</strong></td><td></td><td></td><td></td></tr><tr><td>Mean SBP (mmHg) at inclusion</td><td>124 (120 - 129)</td><td>119 (113 - 123)</td><td>&lt;0.0001</td></tr><tr><td>Mean SBP &lt;120 mmHg at inclusion</td><td>28 (22%)</td><td>42 (58%)</td><td>&lt;0.0001</td></tr><tr><td>Mean SBP &lt; 122.5 mmHg at inclusion</td><td>45 (35%)</td><td>50 (68%)</td><td>&lt;0.0001</td></tr><tr><td>Mean DBP (mmHg) at inclusion</td><td>79 (74 - 82)</td><td>73 (70 - 76)</td><td>&lt;0.0001</td></tr><tr><td>Mean DBP &lt; 74.5 mmHg at inclusion</td><td>33 (25%)</td><td>49 (67%)</td><td>&lt;0.0001</td></tr><tr><td>Mean DBP &lt; 80 mmHg at inclusion</td><td>70 (54%)</td><td>64 (88%)</td><td>&lt;0.0001</td></tr><tr><td>Mean HBPM (120/80) at inclusion</td><td></td><td></td><td>&lt;0.0001</td></tr><tr><td>SBP &lt; 120 and DBP &lt; 80</td><td>25 (19%)</td><td>40 (55%)</td><td></td></tr><tr><td>SBP &lt; 120 and DBP &gt;= 80</td><td>3 (2%)</td><td>2 (3%)</td><td></td></tr><tr><td>SBP &gt;= 120 and DBP &lt; 80</td><td>45 (35%)</td><td>24 (33%)</td><td></td></tr><tr><td>SBP &gt;= 120 and DBP &gt;= 80</td><td>57 (44%)</td><td>7 (10%)</td><td></td></tr><tr><td>Mean HBPM (122.5/74.5) at inclusion</td><td></td><td></td><td>&lt;0.0001</td></tr><tr><td>SBP &lt; 122.5 and DBP &lt; 74.5</td><td>21 (16%)</td><td>39 (53%)</td><td></td></tr><tr><td>SBP &lt; 122.5 and DBP &gt;= 74.5</td><td>24 (18%)</td><td>11 (15%)</td><td></td></tr><tr><td>SBP &gt;= 122.5 and DBP &lt; 74.5</td><td>12 (9%)</td><td>10 (14%)</td><td></td></tr><tr><td>SBP &gt;= 122.5 and DBP &gt;= 74.5</td><td>73 (56%)</td><td>13 (18%)</td><td></td></tr><tr><td><strong>Office BP</strong></td><td></td><td></td><td></td></tr><tr><td>SBP (mmHg) at inclusion</td><td>131.3 ± 12.1 [n=127]</td><td>128.8 ± 12.5</td><td>0.16</td></tr><tr><td>SBP &lt; 140 mmHg at inclusion</td><td>96/127 (76%)</td><td>59 (81%)</td><td>0.48</td></tr><tr><td>DBP (mmHg) at inclusion</td><td>81.9 ± 7.9 [n=127]</td><td>78.4 ± 7.7</td><td>0.003</td></tr><tr><td>DBP &lt; 90 mmHg at inclusion</td><td>113/127 (89%)</td><td>68 (93%)</td><td>0.45</td></tr><tr><td>BP &lt; 140/90 mmHg at inclusion</td><td>92/127 (72%)</td><td>58 (79%)</td><td>0.31</td></tr></tbody></table>

1

2 ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; BB: beta-blocker; CCB =

3 calcium channel blocker.

4 ASMD: absolute standardized mean difference.

5 Values are mean ± SD or median (IQR) for continuous variables and frequency (percentage) for categorical variables.

6 *p-value from t-test or Mann-Whitney test for continuous variables, and chi-square test or Fisher's exact test for categorical variables.

7 ** Some patients declared having dyslipidemia during the course of the trial, although this was not reported at baseline.

9
<table><caption>Table 4: Multivariable logistic models for predicting maintenance of normotension at 1 year</caption><thead><tr><th>Variables</th><th>OR (CI 95 %)</th><th>p-value</th></tr></thead><tbody><tr><td colspan="3"><strong>Model 1</strong></td></tr><tr><td>Mean systolic HBPM at inclusion (for 5 mmHg increase)</td><td>0.72 (0.56 - 0.94)</td><td>0.014</td></tr><tr><td>Mean diastolic HBPM at inclusion (for 5 mmHg increase)</td><td>0.56 (0.41 - 0.77)</td><td>0.0003</td></tr><tr><td>ARB</td><td>0.49 (0.25 - 0.93)</td><td>0.029</td></tr><tr><td>C-index (CI 95%):</td><td>0.773 (0.706 - 0.840)</td><td></td></tr><tr><td colspan="3"><strong>Model 2</strong></td></tr><tr><td>Mean systolic HBPM at inclusion &gt;= 120 mmHg</td><td>0.32 (0.16 - 0.62)</td><td>0.0009</td></tr><tr><td>Mean diastolic HBPM at inclusion &gt;= 80 mmHg</td><td>0.25 (0.11 - 0.57)</td><td>0.001</td></tr><tr><td>ARB</td><td>0.51 (0.27 - 0.97)</td><td>0.039</td></tr><tr><td>C-index (CI 95%):</td><td>0.761 (0.696 - 0.827)</td><td></td></tr><tr><td colspan="3"><strong>Model 3</strong></td></tr><tr><td>Mean systolic HBPM at inclusion &gt;= 122.5 mmHg</td><td>0.39 (0.19 - 0.77)</td><td>0.007</td></tr><tr><td>Mean diastolic HBPM at inclusion &gt;= 74.5 mmHg</td><td>0.24 (0.12 - 0.48)</td><td>&lt;0.0001</td></tr><tr><td>ARB</td><td>0.50 (0.26 - 0.97)</td><td>0.040</td></tr><tr><td>C-index (CI 95%):</td><td>0.769 (0.702 - 0.835)</td><td></td></tr></tbody></table>

OR: odds-ratio; CI: confidence interval.

6 ARB = angiotensin receptor blocker; HBPM = home blood pressure measurements
Stopping antihypertensive treatment in hypertensive patients in primary care: the STOP-trial

Objective

1. Assess the feasibility of discontinuing antihypertensive therapy (AHT) in patients on monotherapy or low-dose dual therapy without cardiovascular risk factors (other than hypertension) without target organ damage

2. Identify factors associated with maintaining normotension without treatment for one year

Methods

Prospective multicenter open-label study

Primary endpoint

Maintaining normotension (<135/85 mmHg) for one year based on home blood pressure measurements (HBPM) (1, 3, 6, 9, and 12 months)

Main results

203 out of 401 screened individuals were included and analysed

<figure><img src="image_4.png" /></figure>

36%

Maintained BP <135/85 mmHg for one year without AHT

Baseline BP levels as measured by HBPM were the most useful variables to predict maintenance of normal BP without AHT at one year (see figure)

Patients with systolic HBPM <120 mmHg had a 60% chance of maintaining a normal BP compared to 23% with systolic HBPM >120 mmHg

ROC curve of SBP and DBP self-measurement at inclusion for non-maintenance of normotension at one year

<figure><img src="image_5.png" /></figure>

Conclusion

* About one-third of individuals on monotherapy or low-dose dual AHT who discontinued treatment maintained controlled BP after one year

* Discontinuing AHT may be considered in selected individuals with HBPM below 120 mmHg, provided close BP monitoring is performed

Graphical Abstract
178x107 mm (DPI)