DISCUSSION
HYpertension
This multicenter randomized controlled trial included patients with established resistant hypertension based on a 24-h ABPM. We found a significant improvement in both resistant hypertension and blood pressure in the intervention+SoC arm and SoC alone arm. In addition, we observed a significant difference in AHD adherence between the arms after 12 months of follow-up, despite the study being terminated early due to a larger improvement of resistant hypertension in the SoC arm during an interim analysis. Given that most patients had uncontrolled blood pressure for years before participation, it is highly unlikely that the observed improvements would have been achieved without their participation in this study. No differences were determined in the prevalence of resistant hypertension or blood pressure values between the intervention+SoC arm and the SoC arm at t12. Without taking the randomization into account, the overall proportion of patients with resistant hypertension decreased by 34.5% after a follow-up period of at least 12 months. This decrease in resistant hypertension was related to an average decrease in SBP of 12.0 mmHg and DBP of 5.5 mmHg over time, which is a larger decrease compared to most other intervention trials [However, our trial includes interesting findings that can be used to improve adherence research in patients with uncontrolled blood pressure.First, the Hawthorne effect has to be taken into account when performing adherence research [As we already expected this effect, we tried to take these changes into account in our power calculation including an improvement of blood pressure control in the SoC arm. However, the Hawthorne effect in our trial was larger than anticipated, which can be derived from the fact that one-third of all eligible patients were not included because of well controlled blood pressure in combination with adherence to all measured AHDs. This increased adherence in the excluded patients may be temporary; however, no follow-up to monitor adherence is available to confirm this.The extent of the Hawthorne effect was also demonstrated in a prospective observational study called RHYME-AD (Resistant HYpertension: Measure Antihypertensive Drugs) [In addition to the Hawthorne effect, our SoC arm also received extra measurements and, for some patients, extra visits as compared to the real SoC. Usually, patients do not have four ABPMs in 1 year combined with DBS sampling. However, it is very difficult to include patients without signing informed consent or subjecting them to study-related measurements. The use of a true SoC group is therefore almost impossible.Third, our posthoc sensitivity analysis identified some issues that were not expected when designing the study. Part of the patients developed an aversion to 24-h ABPMs. This is unfortunate, as this is the most reliable method to establish true blood pressure in patients. Because of this issue, we had to move to other methods to measure blood pressure, such as AOBP [