Reduction In Office Blood Pressure Research Articles

Biomarker response and therapy prediction in renal denervation therapy – the role of MR-proadrenomedullin in a multicenter approach

Background: Renal denervation has been proposed as a therapeutic option in patients with resistant hypertension. Circulating blood borne biomarkers might be helpful to identify individuals responding to RDN therapy. MR-proADM is a strong prognostic marker in patients with cardiovascular disease. The aim of this multicenter study was to evaluate the effect of RDN on MR-proADM concentrations.Methods and results: We measured MR-proADM, BNP, and MR-proANP in 110 patients before and after RDN in a multicenter setting. All patients were followed up after 1 and 6 months by office and ambulatory blood pressure (BP) measurements. The mean office BP decreased from 165/89 to 152/87 mmHg 6 months after RDN (systolic: p < 0.001; diastolic: ns), the responder-rate was 74%. Intriguingly MR-proADM concentrations increased from 0.66 to 0.69 nmol/L (p < 0.001) and were significantly associated with reduction of systolic office BP after 6 months in multivariate analyses (coefficient −0.0018, p < 0.001). In therapy-responders MR-proADM concentrations showed a significantly higher increase over time (coefficient 0.0105, p < 0.05), as compared to non-responders. There were no significant differences in BP change for individuals with low and high baseline MR-proADM (BP-Delta low MR-proADM −23/−4 mmHg vs. high MR-proADM −24/−5 mmHg). The natriuretic biomarkers BNP and MR-proANP did not change significantly after 6 months. Biomarkers at baseline were not able to predict for therapy-responder.Conclusion: In patients undergoing RDN, baseline measurements of various biomarkers had no prognostic use for therapy success in this short time follow-up period in a multicenter approach. Intriguingly, MR-proADM showed a significant association with BP reduction after 6 months.

Effect of low-dose spironolactone on resistant hypertension in type 2 diabetes mellitus: a randomized controlled trial in a sub-Saharan African population

BackgroundLow-dose spironolactone has been proven to be effective for resistant hypertension in the general population, but this has yet to be confirmed in type 2 diabetic (T2DM) patients. We assessed the efficacy of a low-dose spironolactone on resistant hypertension in a sub-Saharan African population of T2DM patients from Cameroon.MethodsThis was a four-week single blinded randomized controlled trial in 17 subjects presenting with resistant hypertension in specialized diabetes care units in Cameroon. They were randomly assigned to treatment with a daily 25 mg of spironolactone (n = 9) or to an alternative antihypertensive regimen (n = 8), on top of any ongoing regimen and prevailing lifestyle prescriptions. They were seen at the start of the treatment, then 2 and 4 weeks later. The primary outcome was change in office and self-measured blood pressure (BP) during follow-up, and secondary outcomes were changes in serum potassium, sodium, and creatinine levels.ResultsCompared with alternative treatment, low-dose spironolactone was associated with significant decrease in office systolic BP (−33 vs. −14 mmHg; p = 0.024), and in diastolic BP (−14 vs. −5 mmHg; p = 0.006). After 1 month of spironolactone, all the patients were controlled based on BP below 130/80 mmHg, with significant office BP reduction from 158 ± 17/86 ± 11 to 125 ± 11/72 ± 8, vs. 158 ± 8/94 ± 8 to 144 ± 17/89 ± 12 mmHg in the alternative treatment group. There was no significant variation in sodium and creatinine levels in both groups, but a mild increase of potassium levels in the spironolactone group.InterpretationAdd-on low-dose spironolactone was effective in reducing BP to optimal levels in T2DM Cameroonian patients despite mild increase in serum potassium.Trial registration ClinicalTrials.gov Identifier NCT02426099. Date of registration April 2015

Renal denervation for resistant hypertension: no.

In recent years, catheter-based radiofrequency denervation of the renal arteries (RDN) has emerged as a potential treatment for resistant hypertension. Though initial non-randomized and randomized small studies demonstrate large reductions in office blood pressure, RDN superiority to conventional treatment is not confirmed either by randomized controlled trials or by large international registries. Increasing evidence supports the hypothesis that a rational pharmacological therapeutic scheme is equally or more effective; this approach, together with an intervention aimed at increasing patient's compliance with treatment, might solve most of the cases of refractory hypertension. Thus, based on current evidence, renal denervation should not be routinely used to treat resistant hypertension. Though the possibility that RDN might be useful in other subsets of hypertensive patients exists, it has never been proven. Thus, its use should be limited to extreme situations, when all other possible treatments have failed.

Case Report: Renal Sympathetic Denervation + Pulmonary Vein Reisolation in Patients with Long-stand Persistent Atrial Fibrillation and Resistant Hypertension. Does it Work?

Introduction: A recent study reported that renal sympathetic denervation (RSD) reduces systolic and diastolic blood pressure (BP) in patients with drug-resistant hypertension and reduces atrial fibrillation (AF) recurrences when combined with pulmonary vein isolation (PVI), in a prospective randomized study that assessed the impact of renal artery denervation in patients with a history of refractory AF and drug-resistant hypertension who were referred for PVI. Case presentation: In this series of cases of long-standing persistent atrial fibrillation (LSPAF) we report 5 cases refractory to treatment with antiarrhythmic drug that underwent to AF catheter ablation, at least one year. The five patients complained about tachycardic palpitations often, as well as, episodes of dyspnea and pre-syncope, were taking amiodarone 200 mg/day and returned to present LSPAF. Moreover, all of them had resistant hypertension besides to possessing other comorbidities. They had normal renal function, and were using the anti-hypertensive medications for at least 3 months, as well as all of them were using dabigatran 150 mg twice a day. All of them underwent to pulmonary vein re-isolation (PVRI) and RSD. All the patients submitted to RSD showed highly significant reduction in office BP and 24-hour APM, both systolic and diastolic at all times points after the procedure. No changes in the renal function were observed before and after the procedure. Even after prompt successful PVRI + RSD procedures, with the 5 patients recovering sinus rhythm, all of them had recurrence of persistent AF in less than one year. After controlling the BP, even all the individuals being in AF, we observed a reduction in left atrial volume at one year post procedure (P = 0.0008), measured by cardiac magnetic resonance. Due to the maintenance of AF we opted to maintain amiodarone and think a third ablation of this arrhythmia in the future with more aggressive strategies or even opt for the control of heart rate, depending on the symptoms of patients. Conclusions: We can conclude that RSD was effective in controlling BP and associated to PVRI showed a reduction in volume of the left atrium, but in the control of LSPAF, we did not achieve the success.

Quantifying the 3 Biases That Lead to Unintentional Overestimation of the Blood Pressure-Lowering Effect of Renal Denervation.

Studies of renal denervation report disparate results. Meta-analysis by trial design may allow quantitative estimation of sources and magnitude of biases in denervation studies. One hundred forty nonrandomized, 6 randomized open-label, and 2 randomized blinded studies were analyzed for 2 outcomes: (1) blood pressure changes for nonrandomized, open-label randomized, and blinded studies; and (2) quantification of 3 biases potentially contributing to apparent antihypertensive effects: (a) regression to the mean, (b) asymmetrical data handling, and (c) true blood pressure drops caused by something other than the tested therapy (confounding). Nonrandomized studies and open-label randomized trials reported large reductions in office blood pressure of 23.6 mm Hg (95% confidence interval [CI], 22.0 to 25.3) and 29.1 mm Hg (95% CI, 25.2 to 33.1 mm Hg), respectively. They reported smaller reductions in ambulatory blood pressures (11.2 mm Hg; 95% CI, 10.0 to 12.4). The blinded trials found no significant reduction in blood pressure (2.9 mm Hg; 95% CI, -0.4 to 6.3). Analyses of these data indicate the magnitude of the 3 potential sources of bias to be regression to the mean, -1.01 mm Hg (95% CI, 4.24 to -6.27); asymmetrical data handling, -10.8 mm Hg (95% CI, -8.77 to -12.87); and confounding, -8.3 mm Hg (95% CI, -4.73 to -11.83). Increasingly bias-resistant trial designs report effect sizes of decreasing magnitude. This disparity may be caused by asymmetrical data handling and confounding (eg, increased drug adherence). If these differences are caused by trial design and not by some other differences in patients or procedures, which happen to match the trial design, then randomization alone is not enough: blinding is also needed. This has broad implications across trials of medications and devices.

Comparison of continuous positive airway pressure and bosentan effect in mildly hypertensive patients with obstructive sleep apnoea: A randomized controlled pilot study

Randomized controlled trials (RCT) have shown that continuous positive airway pressure (CPAP) has only limited impact on blood pressure (BP). Alternative strategies for obstructive sleep apnoea (OSA)-associated hypertension are therefore needed. Endothelin-1 has been demonstrated a key player in the deleterious cardiovascular consequences of OSA. In OSA, CPAP treatment has never been compared with endothelin receptor antagonist medications. Thus, we assessed the respective efficacy of CPAP and bosentan in reducing 24-h diastolic BP (DBP) in patients with OSA never treated by either therapy. In a crossover pilot study, 16 mildly hypertensive patients (office systolic BP (SBP)/DBP: 142 ± 7/85 ± 8 mm Hg) with severe OSA (55 ± 8 years; body mass index, 29.6 ± 4.2 kg/m(2) ; apnoea-hypopnoea index, 40.8 ± 20.2/h) were randomized to either CPAP (n = 7) or bosentan (125 mg/day, n = 9) first for 4 weeks. After 2-weeks of washout, the second 4-week period consisted of the alternative treatment (in crossover). The primary outcome was the 24-h mean DBP change after treatment. In intention-to-treat analysis, the mean difference in 24-h DBP measurements between treatments was -3.1 (-6.9/0.7) mm Hg (median, 25th/75th percentiles) (P = 0.101) with bosentan having a greater effect. In this RCT, in mildly hypertensive patients with OSA, bosentan did not modify 24-h DBP but only reduced office BP suggesting that Endothelin-1 blockade does not play a major role in treatment of OSA-related hypertension.

Blood pressure changes after catheter-based renal denervation are related to reductions in total peripheral resistance.

Renal denervation (RDN) can reduce sympathetic activity and blood pressure (BP) in patients with uncontrolled hypertension. The exact mechanisms by which RDN results in BP reductions are yet not fully established. This study investigated the effects of RDN on office BP, 24-h ambulatory BP, noninvasive 10-min beat-to-beat digital pulse wave analysis, total peripheral resistance (TPR), cardiac output, and plasma renin and aldosterone serum concentrations in 30 patients with resistant hypertension. Adherence to antihypertensive drugs was assessed by liquid chromatography high-resolution tandem mass spectrometry analysis in plasma and urine at baseline and at 6 month. RDN significantly reduced office BP, beat-to-beat BP, and 24-h ambulatory BP by 19/6 (P = 0.021/P = 0.012), 12/7 (P = 0.005/P = 0.005), and 10/5 mmHg (P = 0.001/P = 0.049) at 6 months, respectively. TPR decreased from 1696 to 1377 dyn × s/cm (-19%; P = 0.027). This reduction was not associated with significant changes in cardiac output. The changes in office, ambulatory, and beat-to-beat BP correlated with the reductions of TPR. Adherence to antihypertensive treatment remained unchanged during the study period (84.7% at baseline, 83.6% at 6 months, P = 0.782). RDN reduced office BP, beat-to-beat BP, and 24-h ambulatory BP in patients with resistant hypertension after 6 months. The BP changes were associated with reductions in peripheral resistance, whereas cardiac output, plasma renin, and aldosterone levels remained unchanged. The observed effects were not explained by an increased intake of antihypertensive medications.

Blood pressure variability after catheter-based renal sympathetic denervation in patients with resistant hypertension.

Renal denervation (RDN) reduces sympathetic activity and blood pressure (BP) in patients with resistant hypertension. Increased 24-h BP variability is associated with adverse cardiovascular outcomes and related to sympathetic activation. This multicenter study investigated the effect of RDN on BP variability in 84 patients with uncontrolled hypertension (office systolic BP ≥140 mmHg) despite treatment with greater than three antihypertensive agents. BP variability was assessed by means of standard deviation, coefficient of variation (standard deviation/mean), and average real variability of 24-h ambulatory SBP at 3-month and 6-month follow-up. RDN significantly reduced office BP by 17/6 mmHg at 3-month and 19/7 mmHg at 6-month follow-up (P < 0.001 for all) and 24-h ambulatory BP by 9/5 mmHg (P < 0.001/P = 0.001) after 3 months and 12/7 mmHg (P < 0.001/P < 0.001) after 6 months. Standard deviation significantly decreased from 17.1 to 14.9 mmHg (P = 0.008) and 15.3 mmHg (P = 0.037), consistent with a reduction of coefficient of variation from 0.116 to 0.103 (P = 0.035) and 0.104 (P = 0.071) and average real variability from 12.3 to 10.9 (P = 0.029) and 11.0 (P = 0.054) after 3-month and 6-month, respectively. Interestingly, also BP nonresponders (change in office systolic BP < 10 mmHg after 6 months) showed a significant reduction of standard deviation after 3 months (P = 0.041, n = 26) and a borderline significant reduction at 6-month (P = 0.057, n = 28). RDN reduces office and ambulatory BP and BP variability in patients with resistant hypertension. Improvement in BP variability was also documented in patients characterized as office BP nonresponders after 6 months.

Abstract 15342: Does Ivabradine Affect Sympathetic Overdrive and Arterial Stiffening in Hypertensive Patients With Metabolic Syndrome?

Introduction: Hypertension and metabolic syndrome are related to sympathetic overdrive and arterial stiffening, while there are no data whether ivabradine modulates sympathetic activity and vascular abnormalities in this setting. Hypothesis: To assess the effect of ivabradine on muscle sympathetic nerve activity (MSNA) and arterial stiffness in hypertensive patients with metabolic syndrome. Methods: We studied 36 patients with essential hypertension [age: 56±10 years, 30 males, office blood pressure (BP): 148/92±14/11 mmHg] on antihypertensive therapy with a fixed combination of perindopril/amlodipine. Patients were randomized with a ratio 2:1 to ivabradine (5 mg twice daily) or no ivabradine (control group). Metabolic syndrome was defined according to the Adult Treatment Panel III criteria. In all participants at baseline and at 6 months follow-up arterial stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (PWV) while sympathetic drive was assessed by MSNA estimations based on established methodology (microneurography). Results: Patients on ivabradine (n=24) compared to controls (n=12) did not differ regarding baseline BP, creatinine, glucose and lipid profile (p=NS or all). There was no significant difference in the reduction of office BP between the two study groups (p=NS). However, hypertensive patients in the ivabradine group were characterized by a reduction in carotid to femoral PWV from 11.5±0.9 m/sec to 9.8±1.2 m/sec (p&lt;0.001) and sympathetic nerve traffic as reflected by MSNA levels from 86.2±2.5 bursts per 100 heart beats to 74.8±2.4 bursts per 100 heart beats (p&lt;0.001) at 6 months. No significant changes in PWV and MSNA were observed in the control group (p=NS). Conclusions: In hypertensive patients with metabolic syndrome, treatment with ivabradine reduces sympathetic activation and arterial stiffening as reflected by lower MSNA and PWV levels at 6 months follow-up. These findings suggest that ivabradine could exhibit additional therapeutic properties in the setting of dysmetabolic hypertension.

Abstract 13281: Effect of Arteriovenous Anastomosis on Blood Pressure Reduction in Patients With Isolated Systolic Hypertension Compared to Combined Hypertension

Background: Several interventional therapeutic options for blood pressure (BP) lowering in patients with treatment-resistant hypertension (TRH) were introduced, such as renal denervation (RDN) and creation of an arteriovenous (AV) anastomosis using the ROX coupler. It was shown that BP response after RDN is greater in patients with combined hypertension (CH) compared to patients with isolated systolic hypertension (ISH). We analyzed now the effect of ROX coupler implantation in the subgroups with CH and ISH. Methods: The randomized, controlled, ROX CONTROL HTN study included patients with true TRH (office systolic BP ≥140mmHg, and average daytime ambulatory BP ≥135/85mmHg, despite treatment with at least 3 antihypertensive drugs including a diuretic). In our post-hoc analysis we have stratified the patients of the ROX coupler group (n=42) according CH (n=31) versus ISH (n=11). Results: Baseline systolic office (177±18 versus 169±17 mmHg, p=0.163) and ambulatory BP (159±16 versus 154±11 mmHg, p=0.463) did not differ between CH and ISH. Creation of an AV anastomosis resulted in a significant reduction in systolic office (CH: -28±22 versus ISH: -22±31 mmHg, p=0.572) as well as ambulatory BP (CH: -14±20 versus ISH: -13±15 mmHg, p=0.672), but without significant differences between the two subgroups. The non-responder rate (systolic office BP reduction &lt; 10 mmHg) after 6 months was not different between the subgroups (CH: 18 % versus ISH: 23 %, p=0.844). Conclusions: Thus, our data suggest that creation of an AV anastomosis using the ROX coupler reduces systolic office and ambulatory BP, without any significant difference between CH and ISH. In contrast to RDN, creation of an AV anastomosis reduced BP to similar extent in both subtypes of TRH.

Оцінка впливу фіксованої комбінації периндоприл + амлодипін на ураження органів-мішеней у пацієнтів з артеріальною гіпертензією (первинні результати дослідження EPHES)

Дослідження EPHES (Evaluation of influence of fixed dose combination Рerindopril/Amlodipine on target organ damage in patients with arterial HypErtension with or without iSchemic heart disease) мало за мету оцінити ефективність фіксованої комбінації периндоприл + амлодипін щодо зниження артеріального тиску (АТ) та динаміки вираженості ураження органів-мішеней у хворих на артеріальну гіпертензію (АГ) з ішемічною хворобою серця (ІХС) та без такої. У первинний аналіз включено дані 30 пацієнтів з АГ без ІХС віком понад 30 років. Рівень систолічного (САТ) і/або діастолічного (ДАТ) АТ у хворих, що до цього не лікувалися, на момент включення мав бути ≥ 160 та/або 100 мм рт.ст., але &lt; 200/120 мм рт.ст.; у тих, хто знаходився на монотерапії або подвійній комбінованій терапії, — ≥ 140/90 мм рт.ст., але &lt; 200/120 мм рт.ст. Усім пацієнтам у день рандомізації призначали фіксовану комбінацію периндоприл + амлодипін у початковій дозі 5/5 мг один раз на добу. При необхідності (АТ &gt; 140/90 мм рт.ст.) дози компонентів фіксованої комбінації збільшували поступово кожні 2 тижні до 10/10 мг, а після 6 тижнів лікування додавали індапамід 1,5 мг, бета-адреноблокатори або альфа-адреноблокатори. Усім пацієнтам проводили: вимірювання маси тіла та зросту, офісних рівнів САТ, ДАТ та частоти серцевих скорочень, добове моніторування АТ, визначення швидкості поширення пульсової хвилі в артеріях еластичного (ШППХе) та м’язового типів, центрального САТ, біохімічне дослідження крові, електрокардіографію, ехокардіографію з Д-графією, вимірювання гомілково-плечового індексу, визначення товщини комплексу інтима-медіа. Тривалість спостереження становила 12 місяців.Лікування за допомогою фіксованої комбінації периндоприл + амлодипін забезпечувало досягнення цільового рівня і САТ, і ДАТ у 60 % випадків на етапі 6 тижнів. Додавання індапаміду 1,5 мг на добу (n = 12) та бісопрололу (n = 1) забезпечило контроль офісного САТ і ДАТ у 100 % пацієнтів на етапі 6 місяців лікування. Зниження офісного АТ супроводжувалося достовірним зменшенням середньодобового, денного та нічного АТ відповідно на 22,3 ± 0,1 мм рт.ст., 19,6 ± 0,4 мм рт.ст., 26,1 ± 0,2 мм рт.ст. та 8,2 ± 0,2 мм рт.ст., 8,4 ± 0,1 мм рт.ст., 7,9 ± 0,1 мм рт.ст. і досягненням цільового середньодобового АТ у 98,7 % пацієнтів. Достовірно зменшилася частка пацієнтів, які характеризувалися як «нон-діппери», з 50 до 23,3 % та варіабельність денних САТ/ДАТ та нічного САТ. Частка пацієнтів із величиною ранкового підйому САТ понад 55 мм рт.ст. достовірно зменшилася з 60 до 20 %. Центральний САТ достовірно знизився з 142,8 ± 2,5 мм рт.ст. до 118,3 ± 2,7 мм рт.ст. (Р &lt; 0,001). Паралельно відбулося достовірне (Р &lt; 0,001) зменшення індексу приросту з 26,8 ± 1,9 % до 11,2 ± 1,7 %. Ефективна щодо зниження АТ терапія протягом року призводила до достовірного регресу ураження органів-мішеней: зменшення гіпертрофії лівого шлуночка (індекс маси міокарда зменшився з 108,8 ± 5,5 г/м2 до 88,3 ± 5,3 г/м2, індекс Корнелла — з 2440,1 ± 67,9 мм • мс до 1987,2 ± 66,8 мм • мс, розмір лівого передсердя — з 41,1 ± 0,2 мм до 38,1 ± 0,3 мм), рівня альбумінурії (з 53,3 ± 5,6 мг/добу до 15,8 ± 3,2 мг/добу), покращенню діастолічної функції лівого шлуночка та пружно-еластичних властивостей аорти (­ШППХе зменшилася з 11,9 ± 0,7 м/с до 9,4 ± 0,8 м/с). Зміни діастолічної функції лівого шлуночка та рівня альбумінурії достовірно та незалежно від змін рівня АТ (і офісного, і центрального) корелювали зі змінами ШППХе та індексу приросту. Проведена антигіпертензивна терапія на основі фіксованої комбінації периндоприл + амлодипін добре переносилася хворими (частота побічних реакцій 6,5 %).

Safety and performance of the next generation EnligHTN™ renal denervation system in patients with drug-resistant, uncontrolled hypertension: The EnligHTN III first-in-human multicentre study

Background/objectivesCatheter-based renal denervation for the treatment of drug-resistant hypertension has been intensively investigated in recent years. To date, only limited data have been published using multi-electrode radiofrequency ablation systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and efficacy of the next generation EnligHTN™ renal denervation system. Six-month primary endpoint data are presented here. MethodsWe conducted this first-in-human, prospective, multi-center, non-randomized study in 39 patients (62% male, mean age 63years, and mean baseline office blood pressure 174/93mmHg) with drug-resistant hypertension. The primary safety and efficacy objectives were to characterize, from baseline to 6months post-procedure, the rate of serious procedural and device related adverse events, as adjudicated by an independent Clinical Events Committee, and the reduction of office systolic blood pressure. ResultsRenal artery denervation, using the next generation EnligHTN multi-electrode system significantly reduced office blood pressure from baseline to 1, 3, and 6months by −19/7, −26/9 and −25/7mmHg, respectively (P≤0.0005). No serious device or procedure related adverse events affecting the renal arteries or renal function occurred through. ConclusionsRenal sympathetic denervation using the next generation EnligHTN renal denervation system resulted in safe, rapid, and significant mean office blood pressure reduction that was sustained through 6months. Future studies will need to address the utility of this system against an appropriate placebo based comparator.

4A.03

Objective: The EnligHTN I, the first-in-human study using a multielectrode ablation system for renal denervation (RDN) in patients with drug resistant hypertension (dRHT) demonstrated efficacy and safety at 6 and 12 months. The aim of this study was to report the complete set of 24 month data on office, ambulatory and home blood pressure (BP) changes as well as long term safety. Design and method: We studied 46 patients (age: 60±10 years, 4.7 ± 1.0 antihypertensive drugs, body mass index: 32 ± 5 kg/m2) with dRHT on >or=3 antihypertensive medications who had a systolic BP>or=160 mmHg (>or=150 mmHg for diabetics). At baseline, the average office BP, 24-hour ambulatory BP and home BP were 176 ± 16/96 ± 14 mmHg, 150 ± 14/83 ± 13 mmHg and 158 ± 16/90 ± 12 mmHg respectively. Bilateral RDN was performed using percutaneous femoral approach and standardized techniques. Results: Reduction in office BP at 18 and 24 months from baseline were -24/-10 mmHg and -29/-13 mmHg, while the reduction in 24-hour ambulatory BP and in home BP at 24 months were -13/-7 mmHg and -11/-6 mmHg respectively (p < 0.05 for all). Apart from higher body mass index (33.3 ± 4.7 vs 29.5 ± 6.2 kg/m2, p < 0.05), there were no differences in age, baseline office BP, heart rate, diabetes mellitus and baseline antihypertensive drug therapy in patients that were RDN responders at 24 months [defined as 10 mmHg decline in office BP compared to baseline (74%, n = 34)]. Stepwise logistic regression analysis revealed no prognosticators of RDN response (p = NS for all). At 24 months apart from a trend for renal function decrease, there were no new serious or life-threatening adverse events related with the procedure. Conclusions: The EnligHTN I study provides evidence that the multielectrode ablation system constitutes a safe method of RDN in patients with dRHT and is accompanied by a sustained reduction of office, ambulatory and home BP at 24 months after the procedure. However, no predictors of RDN response were identified at long term follow-up.

PP.40.10

Objective: to evaluate the factors effecting the blood pressure (BP) reduction and glycemic control improvement of patients with resistant hypertension (RH) with type 2 diabetes mellitus (T2DM). Design and method: Thirty two true resistant hypertensive patients with T2DM were included in single-arm prospective interventional study (detailed protocol was published on ClinicalTrial.gov, number NCT01499810). TRD was performed as bilateral transluminal radiofrequency ablation of neural pathways adjacent to renal artery. Office BP measurement, ambulatory 24-h BP monitoring (ABPM), renal Doppler ultrasound and assessment of renal function (proteinuria, creatinine, eGFR, volume of 24-hour urine, levels of K, Na in 24-hour urine), plasma HbA1c levels, basal glycaemia levels, levels of epinephrine in 24-h urine, plasma aldosterone levels and plasma renin activity levels were performed at baseline and 6 months after TRD. On average, patients were taking 4 (3–5) antihypertensive drugs. None of the patients changed the antihypertensive and antidiabetic treatments during follow-up. A 6 months follow-up was completed by 27 patients (43–75 years old, mean aged 59.3 ± 7.9 years, 14 male). Results: A significant reduction of average systolic office and 24-hour BP (from 173.7 ± 20.8 to 149.9 ± 19.4mmHg, p < 0.001 and from 160.8 ± 18.4 to 147.9 ± 16.9mmHg, p < 0.01, respectively) without any negative effect on renal function. Eighteen patients (67%) were responders with an SBP reduction > 10mmHg according to office measurement and 15 pts (56%) were responders according to ABPM. Six months later after RD 8 patients (30%) had the goal office SBP (p = 0.07), although 1 patient kept SBP>180mmHg. Also, there was observed significant reduction of mean HbA1c level after a 6-month follow-up (from 6.9 ± 1.8% to 5.8 ± 1.5%, p = 0.04). Both dynamics 24-hour SBP and HbA1c levels had inverse relationship to dynamics of 24-hour natriuresis (r = -0.69, p = 0.006 and r = -0.86, p = 0.01). Other relationships were not found. Conclusions: BP reduction and glycemic control improvement after the renal denervation of patients with resistant hypertension and diabetes mellitus were associated with growth of natriuresis, which reflects evidence of sympathetic tonus decrease and renal denervation effectiveness. Moreover, our data confirm that antihypertensive action of RD of these patients is implemented for the most part via natriuresis stimulation.

9C.07

Objective: According to the 2013 ESH/ESC guidelines combination drug treatment is recommended in the treatment of isolated systolic hypertension (ISH) to improve blood pressure (BP) control. The present study was aimed at comparing the antihypertensive effects, tolerability and side effects profile of nebivolol/hydrochlorothiazide vs irbesartan/hydrochlorothiazide combination in elderly patients with ISH. Design and method: 124 ISH patients aged 69.1 ± 3.1 (mean ± SEM) followed by 13 general practictioners in Netherlands and Belgium were enrolled and randomized in a double blind fashion to Nebivolol 5 mg/Hydrochlorothiazide 12.5 mg (NH, n = 62) or Irbesartan 150 mg/Hydrochlorothaizide 12.5 (IH,N = 62) once daily for a 12 week period on sitting office BP, ambulatory BP, 24 hour BP variability, pulse pressure, tolerability and safety profile. Results: 9 pts were withdrawn after randomization. After 12 weeks NH caused a significant greater reduction than IH in sitting SBP (-25.8 ± 1.6 vs -20.6 ± 1.7 mmHg, P < 0.03) and heart rate (HR, -7.0 ± 1.0 vs 2.5 ± 1 b/min, P < 0.01), while the decrease in diastolic and pulse BP showed a non significant tendency to be greater in NH than in IH (-7.4 ± 1.0 and -18.3 ± 1.5 vs -5.0 ± 0.09 and -15.7 ± 1.7 mmHg, P = NS for both). The magnitude of the 24-h, day-time and night-time SBP reduction was almost superimposable in the 2 groups, while HR reduction induced by NH was significantly (P < 0.001) greater during the 24-h, the daytime as well as the nighttime period than that induced by IH. NH caused a significantly greater reduction than IH in 24-h SBP variability, both when expressed as standard deviation (-4.4 ± 2.7 ± vs -2.2 ± 5.1 mmHg, P < 0.02) or as coefficient of variation (-2.0 ± 2.6 vs -0.3 ± 3.4, P < 0.01). This was the case also for pulse pressure and mean BP. Both the 2 drug combinations were well tolerated. Conclusions: These data provide evidence that NH induces an office BP reduction greater than IN but similar effects throughout the 24 hours. NH, however, reduces, at variance from IH, 24-h systolic, mean and pulse BP variability, suggesting a greater protection against a variable known to adversely affect morbidity and mortality in hypertensive patients.

LB02.02

Objective: Several interventional therapeutic options for blood pressure (BP) lowering in patients with treatment-resistant hypertension (TRH) were introduced, such as renal denervation (RDN) and creation of an arteriovenous (AV) anastomosis using the ROX coupler. It was shown that BP response after RDN is greater in patients with combined hypertension (CH) compared to patients with isolated systolic hypertension (ISH). We analyzed now the effect of ROX coupler implantation in the subgroups with CH and ISH. Design and method: The randomized, controlled, ROX CONTROL HTN study included patients with true TRH (office systolic BP >=140mmHg, and average daytime ambulatory BP >=135/85mmHg, despite treatment with at least 3 antihypertensive drugs including a diuretic). In our post-hoc analysis we have stratified the patients of the ROX coupler group (n = 42) according CH (n = 31) versus ISH (n = 11). Results: Baseline systolic office (177 ± 18 versus 169 ± 17 mmHg, p = 0.163) and ambulatory BP (159 ± 16 versus 154 ± 11 mmHg, p = 0.463) did not differ between CH and ISH. Creation of an AV anastomosis resulted in a significant reduction in systolic office (CH: −28 ± 22 versus ISH: −22 ± 31 mmHg, p = 0.572) as well as ambulatory BP (CH: −14 ± 20 versus ISH: −13 ± 15 mmHg, p = 0.672), but without significant differences between the two subgroups. The non-responder rate (systolic office BP reduction < 10 mmHg) after 6 months was not different between the subgroups (CH: 18 % versus ISH: 23 %, p = 0.844). Conclusions: Thus, our data suggest that creation of an AV anastomosis using the ROX coupler reduces systolic office and ambulatory BP, without any significant difference between CH and ISH. In contrast to RDN, creation of an AV anastomosis reduced BP to similar extent in both subtypes of TRH.

Atrial Remodeling Following Catheter-Based Renal Denervation Occurs in a Blood Pressure- and Heart Rate-Independent Manner.

This study sought to investigate left atrial (LA) remodeling in relation to blood pressure (BP) and heart rate (HR) after renal sympathetic denervation (RDN). In addition to reducing BP and HR in certain patients with hypertension, RDN can decrease left ventricular (LV) mass and ameliorate LV diastolic dysfunction. Before and 6 months after RDN, BP, HR, LV mass, left atrial volume index (LAVI), diastolic function (echocardiography), and premature atrial contractions (PAC) (Holter electrocardiogram) were assessed in 66 patients with resistant hypertension. RDN reduced office BP by 21.6 ± 3.0/10.1 ± 2.0 mm Hg (p < 0.001), and HR by 8.0 ± 1.3 beats/min (p < 0.001). At baseline, LA size correlated with LV mass, diastolic function, and pro-brain natriuretic peptide, but not with BP or HR. Six months after RDN, LAVI was reduced by 4.0 ± 0.7 ml/kg/m(2) (p < 0.001). LA size decrease was stronger when LAVI at baseline was higher. In contrast, the decrease in LAVI was not dependent on LV mass or diastolic function (E/E' or E/A) at baseline. Furthermore, LAVI decreased without relation to decrease in systolic BP or HR. Additionally, occurrence of PAC (median of >153 PAC/24 h) was reduced (to 68 PAC/24 h) by RDN, independently of changes in LA size. In patients with resistant hypertension, LA volume and occurrence of PAC decreased 6 months after RDN. This decrease was independent of BP and HR at baseline or the reduction in BP and HR reached by renal denervation. These data suggest that there is a direct, partly BP-independent effect of RDN on cardiac remodeling and occurrence of premature atrial contractions.

Effects of thiazide-type and thiazide-like diuretics on cardiovascular events and mortality: systematic review and meta-analysis.

Thiazide diuretics are recommended as first-line therapy for hypertension and are among the most commonly prescribed drugs worldwide. According to their molecular structure, thiazide diuretics can be divided in thiazide-type (TT) and thiazide-like (TL) diuretics. TL diuretics have a longer elimination half-life compared with TT diuretics and have been shown to exert additional pharmacological effects, which may differently affect cardiovascular risk. In this meta-analysis, we compared the effects of TT and TL diuretics on cardiovascular events and mortality. Randomized, controlled studies in adult hypertensive patients that compared TT or TL diuretics with placebo or antihypertensive drugs and had ≥1 year follow-up were included. Primary outcome was cardiovascular events; secondary outcomes included coronary events, heart failure, cerebrovascular events, and all-cause mortality. Meta-regression analysis was used to identify confounders and correct for the achieved blood pressure reductions. Twenty-one studies with >480 000 patient-years were included. Outcomes were not affected by heterogeneity in age, sex, and ethnicity among included studies, whereas larger blood pressure reductions were significantly associated with increased risk reductions for all outcomes (P<0.001). Corrected for differences in office blood pressure reductions among trials, TL diuretics resulted in a 12% additional risk reduction for cardiovascular events (P=0.049) and a 21% additional risk reduction for heart failure (P=0.023) when compared with TT diuretics. The incidence of adverse events was comparable among TT, TL diuretics, and other antihypertensive therapy. Our data suggest that the best available evidence seems to favor TL diuretics as the drug of choice when thiazide treatment is considered for hypertension.

Incidence of renal artery stenosis after renal denervation in patients with resistant arterial hypertension

Catheter-based ablation of nerves in the adventitia of renal arteries (renal artery denervation [RAD]) using radiofrequency energy can reduce blood pressure (BP) in patients with resistant arterial hypertension (RAH). Occurrence of renal artery stenosis after RAD is still an important concern. We systematically investigated the renal artery anatomy using magnetic resonance imaging (MRI) or computed tomography (CT) angiography in a consecutive series of patients 6 months after RAD. Patients with RAH were treated by RAD after exclusion of secondary causes of hypertension. RAH was defined by a mean systolic office BP >160 mm Hg. Renal artery imaging was performed 6 months after RAD by MRI angiography. In case of any contraindication for MRI, a CT angiography was performed. The primary end point was the incidence of significant renal artery stenosis (‡70% lumen diameter reduction). RAD was performed in 76 patients, and evaluation of renal artery anatomy by MRI (n [ 66; 87%) or CT angiography (n [ 10; 13%) was performed in all patients 6 months after RAD. We found no renal artery stenosis but 2 cases of new nonsignificant stenosis (50% TO 69% lumen diameter reduction). In responders, mean systolic office BP reduction was L30 mm Hg (p <0.001) and mean systolic 24-hour BP reduction was L18 mm Hg (p <0.001). In conclusion, the incidence of significant renal artery stenosis 6 months after RAD seems to be very low. However, late-onset development of nonsignificant renal artery narrowing cannot be excluded in some patients and should be anticipated in the case of RAH relapse or worsening of renal function after successful

12-Month Blood Pressure Results of Catheter-Based Renal Artery Denervation for Resistant Hypertension: The SYMPLICITY HTN-3 Trial

BackgroundResults of the SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial confirmed the safety but not the efficacy of renal denervation for treatment-resistant hypertension at 6 months post procedure. ObjectivesThis study sought to analyze the 12-month SYMPLICITY HTN-3 results for the original denervation group, the sham subjects who underwent denervation after the 6-month endpoint (crossover group), and the sham subjects who did not undergo denervation after 6 months (non-crossover group). MethodsEligible subjects were randomized 2:1 to denervation or sham procedure. Subjects were unblinded to their treatment group after the 6-month primary endpoint was ascertained; subjects in the sham group meeting eligibility requirements could undergo denervation. Change in blood pressure (BP) at 12 months post randomization (6 months for crossover subjects) was analyzed. ResultsThe 12-month follow-up was available for 319 of 361 denervation subjects and 48 of 101 non-crossover subjects; 6-month denervation follow-up was available for 93 of 101 crossover subjects. In denervation subjects, the 12-month office systolic BP (SBP) change was greater than that observed at 6 months (−15.5 ± 24.1 mm Hg vs. −18.9 ± 25.4 mm Hg, respectively; p = 0.025), but the 24-h SBP change was not significantly different at 12 months (p = 0.229). The non-crossover group office SBP decreased by −32.9 ± 28.1 mm Hg at 6 months, but this response regressed to −21.4 ± 19.9 mm Hg (p = 0.01) at 12 months, increasing to 11.5 ± 29.8 mm Hg. ConclusionsThese data support no further reduction in office or ambulatory BP after 1-year follow-up. Loss of BP reduction in the non-crossover group may reflect decreased medication adherence or other related factors. (Renal Denervation in Patients With Uncontrolled Hypertension [SYMPLICITY HTN-3]; NCT01418261)