Blood pressure response to renal denervation is correlated with baseline blood pressure variability: a patient-level meta-analysis

Background: Sympathetic tone is one of the main determinants of blood pressure (BP) variability and treatment-resistant hypertension. The aim of our study was to assess changes in BP variability after renal denervation (RDN). In addition, on an exploratory basis, we investigated whether baseline BP variability predicted the BP changes after RDN. Methods: We analyzed 24-h BP recordings obtained at baseline and 6 months after RDN in 167 treatmentresistant hypertension patients (40% women; age, 56.7 years; mean 24-h BP, 152/90 mmHg) recruited at 11 expert centers. BP variability was assessed by weighted SD [SD over time weighted for the time interval between consecutive readings (SDiw)], average real variability (ARV), coefficient of variation, and variability independent of the mean (VIM). Results: Mean office and 24-h BP fell by 15.4/6.6 and 5.5/ 3.7 mmHg, respectively (P < 0.001). In multivariable-adjusted analyses, systolic/diastolic SDiw and VIM for 24-h SBP/DBP decreased by 1.18/0.63 mmHg (P 0.01) and 0.86/0.42 mmHg (P 0.05), respectively, whereas no significant changes in ARV or coefficient of variation occurred. Furthermore, baseline SDiw (P ¼ 0.0006), ARV (P ¼ 0.01), and VIM (P ¼ 0.04) predicted the decrease in 24-h DBP but not 24-h SBP after RDN. Conclusion: RDN was associated with a decrease in BP variability independent of the BP level, suggesting that responders may derive benefits from the reduction in BP variability as well. Furthermore, baseline DBP variability estimates significantly correlated with mean DBP decrease after RDN. If confirmed in younger patients with less arterial damage, in the absence of the confounding effect of drugs and drug adherence, baseline BP variability may prove a good predictor of BP response to RDN

Sham or no sham control: that is the question in trials of renal denervation for resistant hypertension. A systematic meta-analysis

BACKGROUND: Studies of renal denervation (RDN) in patients with apparent treatment resistant hypertension have been hampered by a number of patient and physician related confounders on blood pressure (BP) including poor drug adherence. It remains uncertain whether RDN lowers BP. We aimed to investigate whether the use of sham control is essential in RDN studies or whether systematic use of 24-hour ambulatory BP provides enough information thereby making an invasive sham control redundant. METHODS: We meta-analyzed randomized controlled trials of the BP response to RDN on top of continued or optimized antihypertensive drugs in patients with resistant hypertension. On top of the randomized trials reviewed earlier, we additionally included three studies, one conducted in Spain (24 patients, RDN vs. spironolactone), one conducted in Denmark (69 patients, sham controlled) and one conducted in Netherlands (139 patients, RDN vs. continued treatment). We analyzed 24-hour ambulatory BP in 3 sham controlled studies vs. 7 no sham controlled studies. RESULTS: The updated meta-analysis of 10 studies showed 3.6 mmHg (p = .45) and 1.0 mmHg (p = .54) reductions in office and in 24-hour systolic BP, respectively. Meta-analysis of 24-hour systolic BP in the 3 sham-controlled studies showed a reduction of 2.18 mmHg (95% confidence intervals (CIs) -4.70 to 0.33 mmHg, n = 396 vs. 230, p = .07). For the 7 no sham controlled studies there was no difference in 24-hour systolic BP (+0.38 mmHg; 95% CIs -5.29 to 6.04 mmHg, n = 215 vs. 245, p = .90). The test for sub-group heterogeneity showed no significant interaction (p = .69). Removing one trial at a time produced confirmatory results. CONCLUSION: The overall meta-analysis of 10 randomized and controlled studies showed no significant effect on BP of RDN in resistant hypertension. Moreover, our analysis does not support the use of sham control but rather suggests extensive use of 24-hour ambulatory BP in studies of RDN in resistant hypertension

Meta-analysis of randomized controlled trials of renal denervation in treatment-resistant hypertension

Objective. The blood pressure (BP)-lowering effect of renal sympathetic nervous denervation (RDN) in resistant hypertension (rHT) shows large variation among studies. Methods. We meta-analyzed summary statistics of randomized clinical trials on RDN in rHT. For continuous outcomes, we assessed heterogeneity by Cochran's Q test and used random-effect models weighted for the inverse of the variance. We assessed safety by assessing the risk of major adverse events from stratified contingency tables. Results. Of 5652 patients screened in seven trials, 985 (17.4%) qualified and were randomized to control (n = 397) or RDN with SYMPLICITY™ catheters (n = 588). Follow-up was 6 months. In both control and RDN patients, antihypertensive treatment was continued or optimized. At enrolment, age averaged 58.1 years, systolic/diastolic office and 24 h BP 168.5/93.3 mmHg and 151.8/86.1 mmHg, respectively, and estimated glomerular filtration rate (eGFR) 79.3 ml/min/1.73 m². For BP outcomes, there was heterogeneity among trials. Pooled effects (control minus RDN) were −4.9/−3.5 mmHg (95% confidence interval, −20.9 to 11.1/−8.9 to 1.9) for office BP, −2.8/−1.5 mmHg (−6.5 to 0.8/−3.3 to 0.4) for 24 h BP and 0.81 ml/min/1.73 m² (−1.69 to 3.30) for eGFR. Removing one trial at a time produced confirmatory results. Adverse events occurred in 7.4% and 9.9% of control and RDN patients, respectively (p = 0.24). Conclusion. In selected rHT patients maintained on antihypertensive drugs, RDN with the SYMPLICITY systems does not significantly decrease BP but is safe. Future trials with next-generation catheters should aim at identifying responders in patients with evidence of sympathetic nervous overactivity