Results and discussion
Of the 136 RH patients enrolled in the REQUIRE trial, 58 were assessed in this analysis. Baseline characteristics of the cohort with available urine data were similar to those of the entire REQUIRE cohort (Supplementary Table At baseline, 55.2% showed good medication adherence (full: 26 patients, greater partial: 6 patients) and 44.8% had poor adherence (lesser partial: 19 patients, none: 7 patients) (Fig. Graphical abstract: Medication adherence at baseline. 55.2% of patients with resistant hypertension showed good adherence, whereas 44.8% showed poor adherenceWe evaluated differences in baseline characteristics between patients with good adherence and poor adherence. In the poor adherence group, age (51.0 ± 9.4 vs 58.5 ± 11.4, Next, we examined the effects of baseline medication adherence on the changes in adherence and ASBP at 3 months post-procedure. Figure Change in medication adherence rate and 24-h ambulatory systolic blood pressure after ultrasound renal sympathetic nerve denervation or sham procedure. Actual value at baseline and 3 months for adherence (In addition, the reduction in ASBP following uRDN compared to sham was −10.1 ± 13.3 mmHg versus −1.9 ± 15.3 mmHg, respectively, in patients with good adherence at baseline (Fig. It was noteworthy that three (21%) of 14 sham-operated patients with poor adherence at baseline showed remarkable ASBP reductions greater than −30 mmHg (Fig. Given the adherence change over time in some patients, an additional analysis was conducted to look at patients that had good adherence at both baseline and 3 months. A significant BP-lowering effect of uRDN was evident in patients who had good baseline medication adherence and maintained good adherence during the observation period (24-h ASBP, 165.2 ± 14.3 mmHg at baseline, 155.3 ± 18.1 mmHg at 3 months, Although the number of patients in this analysis was a bit less than half of the entire REQUIRE cohort, the baseline patient characteristics were similar. These data suggest that the gradual and large BP reduction in the sham group is in part explained by improvement of medication adherence during the observation period. Taken together, it is possible that REQUIRE included many patients who originally had poor BP control due to poor medication adherence and the BP-lowering effect of uRDN was offset by improved medication adherence during the observation period in such patients, particularly in the sham group.This study had limitations. First, the long-term stability of drugs in urine samples has not been confirmed. Second, a qualitative measurement was employed; therefore, information about the exact drug doses could not be obtained. Third, the pharmacokinetic characteristics of the drugs and renal and liver function of patients could have influenced the detection of the compound; and several drugs were not measured because they were not listed in the drug panels able to be measured (Supplementary Table In conclusion, this REQUIRE post-hoc analysis showed that about 45% of Japanese RH patients had poor medication adherence. A significant BP-lowering effect of uRDN could be evident in patients having good baseline medication adherence that was maintained during the observation period. Monitoring and maintaining medication adherence is important for future intervention studies in RH.