Petr Waldauf

Randomized Comparison of Renal Denervation Versus Intensified Pharmacotherapy Including Spironolactone in True-Resistant Hypertension Six-Month Results From the Prague-15 Study

This prospective, randomized, open-label multicenter trial evaluated the efficacy of catheter-based renal denervation (Symplicity, Medtronic) versus intensified pharmacological treatment including spironolactone (if tolerated) in patients with true-resistant hypertension. This was confirmed by 24-hour ambulatory blood pressure monitoring after excluding secondary hypertension and confirmation of adherence to therapy by measurement of plasma antihypertensive drug levels before enrollment. One-hundred six patients were randomized to renal denervation (n=52), or intensified pharmacological treatment (n=54) with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. A significant reduction in 24-hour average systolic blood pressure after 6 months (−8.6 [95% cofidence interval: −11.8, −5.3] mm Hg; P<0.001 in renal denervation versus −8.1 [95% cofidence interval: −12.7, −3.4] mm Hg; P=0.001 in pharmacological group) was observed, which was comparable in both groups. Similarly, a significant reduction in systolic office blood pressure (−12.4 [95% cofidence interval: −17.0, −7.8] mm Hg; P<0.001 in renal denervation versus −14.3 [95% cofidence interval: −19.7, −8.9] mm Hg; P<0.001 in pharmacological group) was present. Between-group differences in change were not significant. The average number of antihypertensive drugs used after 6 months was significantly higher in the pharmacological group (+0.3 drugs; P<0.001). A significant increase in serum creatinine and a parallel decrease of creatinine clearance were observed in the pharmacological group; between-group difference were borderline significant. The 6-month results of this study confirmed the safety of renal denervation. In conclusion, renal denervation achieved reduction of blood pressure comparable with intensified pharmacotherapy.

Role of Adding Spironolactone and Renal Denervation in True Resistant Hypertension: One-Year Outcomes of Randomized PRAGUE-15 Study.

This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension and assessed the effect of spironolactone addition. We present here the 12-month data. A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. Twelve-month results are available in 101 patients. The intention-to-treat analysis found a comparable mean 24-hour systolic blood pressure decline of 6.4 mm Hg, P=0.001 in RDN versus 8.2 mm Hg, P=0.002 in the pharmacotherapy group. Per-protocol analysis revealed a significant difference of 24-hour systolic blood pressure decline between complete RDN (6.3 mm Hg, P=0.004) and the subgroup where spironolactone was added, and this continued within the 12 months (15 mm Hg, P= 0.003). Renal artery computed tomography angiograms before and after 1 year post-RDN did not reveal any relevant changes. This study shows that over a period of 12 months, RDN is safe, with no serious side effects and no major changes in the renal arteries. RDN in the settings of true resistant hypertension with confirmed compliance is not superior to intensified pharmacological treatment. Spironolactone addition (if tolerated) seems to be more effective in blood pressure reduction.

Renal denervation in comparison with intensified pharmacotherapy in true resistant hypertension: 2-year outcomes of randomized Prague-15 study

Objectives: The randomized, multicentre study compared the efficacy of renal denervation (RDN) versus spironolactone addition in patients with true resistant hypertension. We present the 24-month data. Methods: A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline SBP of 159 ± 17 and 155 ± 17 mmHg and average number of drugs 5.1 and 5.4, respectively. Two-year data are available in 86 patients. Spironolactone addition, as crossover after 1 year, was performed in 23 patients after RDN, and spironolactone addition followed by RDN was performed in five patients. Results: Similar and comparable reduction of 24-h SBP after RDN or spironolactone addition after randomization was observed, 9.1 mmHg (P = 0.001) and 10.9 mmHg (P = 0.001), respectively. Similar decrease of office blood pressure (BP) was observed, 17.7 mmHg (P < 0.001) versus 14.1 mmHg (P < 0.001), whereas the number of antihypertensive drugs did not differ significantly between groups. Crossover analysis showed nonsignificantly better efficacy of spironolactone addition in 24-h SBP and office SBP reduction than RDN (3.7 mmHg, P = 0.27 and 4.6 mmHg, P = 0.28 in favour of spironolactone addition, respectively). Meanwhile, the number of antihypertensive drugs was significantly increased after spironolactone addition (+0.7, P = 0.001). Conclusion: In the settings of true resistant hypertension, spironolactone addition (if tolerated) seems to be of better efficacy than RDN in BP reduction over a period of 24 months. However, by contrast to the 12-month results, BP changes were not significantly greater.

Randomized Comparison of Renal Denervation Versus Intensified Pharmacotherapy Including Spironolactone in True-Resistant Hypertension

This prospective, randomized, open-label multicenter trial evaluated the efficacy of catheter-based renal denervation (Symplicity, Medtronic) versus intensified pharmacological treatment including spironolactone (if tolerated) in patients with true-resistant hypertension. This was confirmed by 24-hour ambulatory blood pressure monitoring after excluding secondary hypertension and confirmation of adherence to therapy by measurement of plasma antihypertensive drug levels before enrollment. One-hundred six patients were randomized to renal denervation (n=52), or intensified pharmacological treatment (n=54) with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. A significant reduction in 24-hour average systolic blood pressure after 6 months (−8.6 [95% cofidence interval: −11.8, −5.3] mm Hg; P<0.001 in renal denervation versus −8.1 [95% cofidence interval: −12.7, −3.4] mm Hg; P=0.001 in pharmacological group) was observed, which was comparable in both groups. Similarly, a significant reduction in systolic office blood pressure (−12.4 [95% cofidence interval: −17.0, −7.8] mm Hg; P<0.001 in renal denervation versus −14.3 [95% cofidence interval: −19.7, −8.9] mm Hg; P<0.001 in pharmacological group) was present. Between-group differences in change were not significant. The average number of antihypertensive drugs used after 6 months was significantly higher in the pharmacological group (+0.3 drugs; P<0.001). A significant increase in serum creatinine and a parallel decrease of creatinine clearance were observed in the pharmacological group; between-group difference were borderline significant. The 6-month results of this study confirmed the safety of renal denervation. In conclusion, renal denervation achieved reduction of blood pressure comparable with intensified pharmacotherapy.

Role of Adding Spironolactone and Renal Denervation in True Resistant Hypertension

This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension and assessed the effect of spironolactone addition. We present here the 12-month data. A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. Twelve-month results are available in 101 patients. The intention-to-treat analysis found a comparable mean 24-hour systolic blood pressure decline of 6.4 mm Hg, P=0.001 in RDN versus 8.2 mm Hg, P=0.002 in the pharmacotherapy group. Per-protocol analysis revealed a significant difference of 24-hour systolic blood pressure decline between complete RDN (6.3 mm Hg, P=0.004) and the subgroup where spironolactone was added, and this continued within the 12 months (15 mm Hg, P= 0.003). Renal artery computed tomography angiograms before and after 1 year post-RDN did not reveal any relevant changes. This study shows that over a period of 12 months, RDN is safe, with no serious side effects and no major changes in the renal arteries. RDN in the settings of true resistant hypertension with confirmed compliance is not superior to intensified pharmacological treatment. Spironolactone addition (if tolerated) seems to be more effective in blood pressure reduction.

PREDICTION OF LONG-TERM RENAL DENERVATION EFFICACY

Objective: Diversity of blood pressure response and great variability within studies emphasise the need to identify predictors of renal denervation efficacy. Previous studies identified various predictors within periods of 3–6 months. Design and method: The goal of the current study is to examine the possible predictors of sustained decline of blood pressure after renal denervation in a long-term period of 2 years. Evaluated patients were either randomised in the original Prague-15 study or were pilot patients, meeting the same inclusion criteria of true-resistant hypertension. Patients were considered as responsive when the decline of 24 h systolic blood pressure > 10 mmHg was present 6, 12 and 24 months after the procedure. In addition, analysis for separate visits was performed. Denervation was performed using the unipolar Symplicity® Renal Denervation System. Extensive assessment of computed tomography angiography by numerous measurements including morphology of the renal arteries was performed. Results: A total of 48 patients were analysed with 27 patients suitable for long-term prediction. According to the protocol of the study, spironolactone was added at 12-month follow-up as a crossover and these patients were excluded from long-term analysis. Five of the 27 patients were identified as long-term responders with average 24 h blood pressure decline of 20/9 mmHg. Strongest predictors of BP decline were higher baseline 24 h systolic blood pressure (p = 0.01) and higher diameter of the left renal artery (p = 0.04). Conclusions: Only a minority of denervated patients exhibited sustained blood pressure decline. Higher baseline blood pressure and higher renal artery diameter were the strongest predictors. Our findings thus might theoretically support the actual hypothesis of the necessity to ablate the distal parts of the renal artery (these conditions might allow such ablation to be performed).

[PP.05.36] RENAL DENERVATION IN COMPARISON TO INTENSIFIED PHARMACOTHERAPY IN TRUE RESISTANT HYPERTENSION. TWO-YEAR OUTCOMES OF RANDOMISED PRAGUE-15 STUDY

Objective: This randomised, multicentre study compared the efficacy of renal denervation (RDN) versus spironolactone addition in patients with true resistant hypertension. We present the 24-month data. Figure. No caption available. Design and method: A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomised to RDN and 54 patients to the spironolactone addition, with baseline systolic blood pressure of 159 ± 17 and 155 ± 17 mmHg and average number of drugs 5.1 and 5.4, respectively. Two-year data are available in 86 patients. Spironolactone addition, as crossover after one year, was performed in 23 patients after RDN, and spironolactone addition followed by RDN was performed in 5 patients. Results: Similar and comparable reduction of 24-hour systolic blood pressure after RDN or spironolactone addition after randomisation was observed, 9.1 mmHg (p = 0.001) and 10.9 mmHg (p = 0.001), respectively. Similar decrease of office blood pressure was observed, 17.7 mmHg (p < 0.001) versus 14.1 mmHg (p < 0.001), while the number of antihypertensive drugs did not differ significantly between groups. Crossover analysis showed non-significantly better efficacy of spironolactone addition in 24 h systolic and office systolic blood pressure reduction than RDN (3.7 mmHg, p = 0.27 and 4.6 mmHg in favour of spironolactone addition, p = 0.28, respectively). Meanwhile, the number of antihypertensive drugs was significantly increased after spironolactone addition (+0.7, p = 0.001). Conclusions: In the settings of true resistant hypertension, spironolactone addition (if tolerated) seems to be of better efficacy than RDN in blood pressure reduction over a period of 24 months. However, by contrast to the 12-month results, blood pressure changes are not significantly greater.

[OP.7D.09] THE ROLE OF ADDING SPIRONOLACTONE AND RENAL DENERVATION IN TRUE RESISTANT HYPERTENSION. ONE-YEAR OUTCOMES OF RANDOMIZED PRAGUE-15 STUDY

Objective: This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension (TRH) and assessed the effect of spironolactone addition. We present the 12-month data. Design and method: The entry criteria included office systolic blood pressure (BP) over 140 mmHg, ambulatory 24-hour mean systolic BP over 130 mmHg, treatment with at least 3 antihypertensive drugs including a diuretic, exclusion of secondary hypertension and excluding drug non-compliance. Thus, only patients with TRH were included after thorough examination in three tertiary hypertension centers. After randomization, patients selected for RDN were maintained on baseline medical therapy for 1 year unless changes were considered clinically necessary. Patients selected for intensified medical treatment received baseline medical therapy plus spironolactone (25 mg daily, as generally recommended), if tolerated, and if no contraindications were present. Results: A total of 106 patients with TRH were randomized: 52 patients to RDN and 54 patients to the spironolactone addition, with baseline systolic BP of 159 ± 17 and 155 ± 17 mmHg and average number of drugs 5.1 and 5.4, respectively. Twelve-month results are available in 101 patients. The intention-to-treat analysis found a comparable 24-hour systolic BP decline of 6.4 mmHg, p = 0.001 in RDN versus 8.2 mmHg, p = 0.002 in the pharmacotherapy group. Per-protocol analysis revealed a significant difference of 24-hour systolic BP decline between complete RDN (6.3 mmHg, p = 0.004) and the subgroup where spironolactone was added and this continued within the 12 months (15 mmHg, p = 0.003). See Figure. Renal artery CT angiograms before and after one year post-renal denervation did not reveal any relevant changes. Figure. No caption available. Conclusions: This study shows that, over a period of 12 months, RDN is safe, with no serious side effects and no major changes in the renal arteries. RDN in the settings of TRH with confirmed compliance is not superior to intensified pharmacological treatment. Spironolactone addition (if tolerated) seems to be more effective in BP reduction.

Role of Adding Spironolactone and Renal Denervation in True Resistant HypertensionNovelty and Significance: One-Year Outcomes of Randomized PRAGUE-15 Study

This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension and assessed the effect of spironolactone addition. We present here the 12-month data. A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. Twelve-month results are available in 101 patients. The intention-to-treat analysis found a comparable mean 24-hour systolic blood pressure decline of 6.4 mm Hg, P=0.001 in RDN versus 8.2 mm Hg, P=0.002 in the pharmacotherapy group. Per-protocol analysis revealed a significant difference of 24-hour systolic blood pressure decline between complete RDN (6.3 mm Hg, P=0.004) and the subgroup where spironolactone was added, and this continued within the 12 months (15 mm Hg, P= 0.003). Renal artery computed tomography angiograms before and after 1 year post-RDN did not reveal any relevant changes. This study shows that over a period of 12 months, RDN is safe, with no serious side effects and no major changes in the renal arteries. RDN in the settings of true resistant hypertension with confirmed compliance is not superior to intensified pharmacological treatment. Spironolactone addition (if tolerated) seems to be more effective in blood pressure reduction.

Role of Adding Spironolactone and Renal Denervation in True Resistant HypertensionNovelty and Significance

This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension and assessed the effect of spironolactone addition. We present here the 12-month data. A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. Twelve-month results are available in 101 patients. The intention-to-treat analysis found a comparable mean 24-hour systolic blood pressure decline of 6.4 mm Hg, P=0.001 in RDN versus 8.2 mm Hg, P=0.002 in the pharmacotherapy group. Per-protocol analysis revealed a significant difference of 24-hour systolic blood pressure decline between complete RDN (6.3 mm Hg, P=0.004) and the subgroup where spironolactone was added, and this continued within the 12 months (15 mm Hg, P= 0.003). Renal artery computed tomography angiograms before and after 1 year post-RDN did not reveal any relevant changes. This study shows that over a period of 12 months, RDN is safe, with no serious side effects and no major changes in the renal arteries. RDN in the settings of true resistant hypertension with confirmed compliance is not superior to intensified pharmacological treatment. Spironolactone addition (if tolerated) seems to be more effective in blood pressure reduction.