Percutaneous renal nerve removal (RDN) has been a research hotspot in the field of hypertension treatment in recent years, and with the deepening of clinical research, the safety and efficacy of RDN have been confirmed, and the guidelines have also made relevant recommendations. On April 8, local time, at the 73rd American College of Cardiology Annual Meeting (ACC.24) "Late-Breaking Clinical Trials" session, Dr. David E. Kandzari from the Piedmont Heart Institute in Atlanta announced the results of the TARGET BP I study. The results of the study showed that anhydrous alcohol-mediated Peregrine catheter ablation of RDN met the primary endpoint in patients with drug-refractory or intolerant hypertension, with a significantly greater reduction in 24-hour dynamic systolic blood pressure at 3 months postoperatively compared with the sham group.
Background:
Globally, more than one-third of adults have hypertension, and many have uncontrolled blood pressure, leading to an increased risk of cardiovascular events. An absolute reduction of 5 mmHg in office systolic blood pressure was associated with a 10% reduction in major cardiovascular events.
RDN targets the sympathetic nervous system to lower blood pressure. Alcohol-mediated RDN delivers anhydrous alcohol through the catheter to perivascular vessels, inactivating local nerves without collateral damage and achieving renal sympathetic innervation (Figure 1).
Figure 1 Alcohol-mediated RDN
The study aims to evaluate the safety and efficacy of alcohol-mediated RDN (injection of absolute ethanol into the renal artery perivascular vessels via a Peregrine catheter device) for the treatment of uncontrolled hypertension in adult or elderly patients taking antihypertensive drugs.
Study design
TARGET BP I is an international multicenter, randomized, double-blind, sham-controlled phase 3 prospective study, including patients with hypertension whose blood pressure is still uncontrolled after stable treatment with 2~5 antihypertensive drugs (including diuretics), with an office systolic blood pressure between 150~180mmHg, an office diastolic blood pressure of ≥90mmHg, and a 24-hour dynamic systolic blood pressure between 135~170mmHg (Fig. 2).
After a 4-week lead-in period, patients were randomly assigned in a 1:1 ratio to alcohol-mediated RDN treatment and a sham control group. The primary endpoint was the between-group comparison of the change from baseline in 24-hour ambulatory systolic blood pressure at 3 months postoperatively, with secondary endpoints including mean between-group differences in office blood pressure and ambulatory blood pressure at other times.
Figure 2 Study design
Findings:
A total of 301 patients were enrolled in the Target BP I study, with a mean age of 56 years, 75% male, 23% diabetic, and 20% taking ≥5 antihypertensive drugs (Table 1). The patient's baseline office blood pressure was 146/87 mmHg and the mean 24-hour blood pressure was 164/99 mmHg (Table 2).
Table 1: Baseline characteristics of patients
Table 2 Baseline blood pressure and heart rate
At 3 months of follow-up, the 24-hour mean reduction in systolic blood pressure between anhydrous alcohol-mediated RDN and sham groups was -10 mmHg and -6.8 mmHg, respectively (difference between groups -3.2 mmHg, P=0.049).
Fig. 3 24-hour mean systolic blood pressure drop
There was no significant difference in mean changes in office systolic and diastolic blood pressure at three months between the anhydrous alcohol-mediated RDN and sham groups, with systolic blood pressure reduced by 12.7 mmHg and 9.7 mmHg, respectively (-3.0 mmHg, P=0.173; figure 4) and diastolic blood pressure decreased by 6.9 mmHg and 6.1 mmHg, respectively (-0.78 mmHg, P=0.31; figure 5), respectively.
Fig.4 Changes in dynamic and office systolic blood pressure
Fig.5 Dynamic and office diastolic blood pressure changes
There were no significant differences in prescription change and medication adherence outcomes between the anhydrous alcohol-mediated RDN treatment group and the sham surgery group during the study period (Figure 6). Anhydrous alcohol-mediated RDN therapy has a favorable safety profile with no major clinical events (Table 3).
Figure 6 Prescription changes and medication adherence
Table 3 Security results
Conclusions and discussions
Anhydrous alcohol-mediated RDN met the primary endpoint in drug-refractory or intolerant hypertensive patients, with a significantly greater reduction in 24-hour dynamic systolic blood pressure at 3 months postoperatively compared with a sham control group. However, there was no significant difference in mean change in office systolic and diastolic blood pressure at three months between anhydrous alcohol-mediated RDN and sham groups. Overall, anhydrous alcohol-mediated RDN surgery was safe, with no major clinical events, such as death, stroke, or hypertensive crisis, reported, the researchers said. One patient experienced arterial dissection during the procedure.
Dr. David E. Kandzari, lead author of the study, noted that typically, if a drop in one blood pressure indicator is observed, an overall decline in other measures is expected. In this trial, anhydrous alcohol-mediated RDN treatment achieved meaningful reductions from baseline on all measurements, but the potential difference was weakened due to a large decrease in the control group. There are still many unanswered questions about why the study came to this point, and the researchers plan to work with the U.S. Food and Drug Administration to evaluate the findings and plan next steps.
Shingen:
[1] ACC official website
[2] Trial Reports Mixed Results with Nerve Ablation for High Blood Pressure—New alcohol-based renal denervation system lowered blood pressure, but overall trial raises more questions than answers. ACC.24.April 8, 2024.
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