Renal denervation associated with SBP reduction in meta-analysis of sham-controlled trials
Sham-Controlled Randomized Trials of Catheter-Based Renal Denervation in Patients With Hypertension
Introduction and methods
Conflicting results have been found in randomized trials evaluating the effectiveness of renal sympathetic denervation (RSD) to lower blood pressure (BP) in uncontrolled hypertension [1-4].
While initial trials showed significant BP reductions, three later, randomized, blinded, sham-controlled trials did not show a significant difference between treatment arms [3-5].
The lack of an observed treatment effect was postulated to arise from differences in patient selection criteria, procedural technique, concomitant medical regimens and primary outcomes. In response, smaller sham-controlled trials have been conducted that addressed some of these questions.
This meta-analysis of all available sham-controlled randomized trials (n≥50) evaluated the effect of RSD on BP in patients with uncontrolled hypertension. Patients with hypertension despite optimal and stable antihypertensive treatment regimens were included, as well as those with hypertension but not taking antihypertensive therapy. Primary efficacy outcome was change in 24-hour ambulatory systolic BP (ASBP).
Six trials met inclusion criteria, totaling of 977 participants (582 randomized to RSD and 395 to sham). Four trials permitted continuation of stable optimal medical therapy in both groups, and two trials enrolled patients who did not take antihypertensive medication for at least 3 to 4 weeks before randomization. SYMPLICITY HTN-3 accounted for 54.7% of patients in this meta-analysis.
- RSD showed significantly greater reductions in 24-h ASBP than sham procedures (weighted mean differences [WMD]: -3.65 mmHg, 95%CI: -5.33 to -1.98 mmHg, P<0.001, I²= 0%).
- RSD showed significantly greater reductions in 24-h ambulatory diastolic BP (ADBP) than sham procedures (WMD: -1.71 mmHg, 95%CI: -3.06 to -0.35 mmHg, P=0.01, I²= 38%).
- Daytime ASBP (WMD: -4.07, P<0.001, I²=31%) and daytime ADBP (WMD: -1.57, P=0.008, I²=0%) were also significantly lower after RSD, while nighttime ASBP and ADBP did not significantly differ between RSD and sham-procedures.
- RSD significantly reduced office SBP (WMD: -5.53, P<0.001, I²=0%) and office DBP (WMD: -3.37, P<0.001, I²=0%) as compared with sham-procedures.
- RSD did not significantly impact changes from baseline in eGFR.
- The effect of RSD on ASBP did not depend on whether antihypertensive drugs were taken.
- Second-generation trials, in which more attention was dedicated to procedural technique, showed a significantly greater reduction in daytime ASBP (6.12 vs. 2.14 mmHg, P-interaction: 0.04). This interaction by type of study was not significant for 24-h ASBP, nighttime ASBP or office SBP.
- Five trials reported no major periprocedural adverse events in either treatment group. In SYMPLICITY HTN-3, 1.4% patients in the RSD group and 0.6% in the sham-group reported major adverse events.
This meta-analysis of six sham-controlled randomized trials demonstrates that patients treated with RSD show significantly greater reduction in 24-h ambulatory, daytime ambulatory, and office systolic and diastolic BP, than those who underwent the sham-procedure. This meta-analysis reinforces the importance of incorporating modifications in trial design as in the latest trials. A larger, pivotal trial should be conducted, consistent with the design of second-generation trials included in this analysis, to evaluate the long-term efficacy and safety of RSD in patients with uncontrolled and resistant hypertension.