Effect of Sequential Nephron Blockade versus Dual Renin-Angiotensin System Blockade Plus Bisoprolol in the Treatment of Resistant Hypertension, a Randomized Controlled Trial (Resistant Hypertension on Treatment - ResHypOT).

Introduction: Hypertension is the most important modifiable risk factor for cardiovascular disease and a leading public health concern. Objectives: The primary aim was to compare sequential nephron blockade (SNB) versus dual renin-angiotensin system blockade (DRASB) plus bisoprolol in patients with resistant hypertension to observe reductions in systolic and diastolic blood pressure (SBP and DBP) levels after 20 weeks of treatment. Material and Methods: This trial was an open-label, prospective, randomized, parallel-group, clinical study with optional drug up-titration. Participants were evaluated during five visits at 28-day intervals. Results: The mean age was 55.5 years in the SNB and 58.4 years in the DRASB + bisoprolol group (p=NS). Significant office BP reductions were observed in both groups. SNB group, SBP decreased from 174.5±21.0 to 127.0±14.74 mmHg (p<0.0001), and DBP decreased from 105.3±15.5 to 78.11±9.28 mmHg (p<0.0001). DRASB group, SBP decreased from 178.4±21.08 to 134.4 ± 23.25 mmHg (p<0.0001) and DBP decreased from 102.7±11.07 to 77.33±13.75 mmHg (p<0.0001). Ambulatory blood pressure monitoring (ABPM) showed also significant SBP and DBP reductions in both groups (p<0.0001). Conclusion: In patients with RHTN adherent to treatment, SNB and DRASB plus bisoprolol showed excellent therapeutic efficacy, although SNB was associated with earlier SBP reduction.

Resistant Hypertension On Treatment (ResHypOT): sequential nephron blockade compared to dual blockade of the renin-angiotensin-aldosterone system plus bisoprolol in the treatment of resistant arterial hypertension - study protocol for a randomized controlled trial.

BACKGROUND: Resistant hypertension is characterized when the blood pressure (BP) remains above the recommended goal after taking three antihypertensive drugs with synergistic actions at their maximum recommended tolerated doses, preferably including a diuretic. Identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether acting on the control of intravascular volume or sodium balance, or acting on the effects of the renin-angiotensin-aldosterone system (RAAS) on the kidney. METHODS/DESIGN: This is a randomized, open-label, clinical trial is designed to compare sequential nephron blockade and its contribution to the intravascular volume component with dual blockade of the RAAS plus bisoprolol and the importance of serum renin in maintaining BP levels. The trial has two arms: sequential nephron blockade versus dual blockade of the RAAS (with an angiotensin converting enzyme (ACE) inhibitor plus a beta-blocker) both added-on to a thiazide diuretic, a calcium-channel blocker and an angiotensin receptor-1 blocker (ARB). Sequential nephron blockade consists in a progressive increase in sodium depletion using a thiazide diuretic, an aldosterone-receptor blocker, furosemide and, finally, amiloride. On the other hand, the dual blockade of the RAAS consists of the progressive addition of an ACE inhibitor until the maximum dose and then the administration of a beta-blocker until the maximum dose. The primary outcomes will be reductions in the systolic BP, diastolic BP, mean BP and pulse pressure (PP) after 20 weeks of treatment. The secondary outcomes will evaluate treatment safety and tolerability, biochemical changes, evaluation of renal function and recognition of hypotension (ambulatory BP monitoring (ABPM)). The sample size was calculated assuming an alpha error of 5% to reject the null hypothesis with a statistical power of 80% giving a total of 40 individuals per group. DISCUSSION: In recent years, the cost of resistant hypertension (RH) treatment has increased. Thus, identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether by acting on the control of intravascular volume or sodium balance, or by acting on the effects of the RAAS on the kidney. TRIAL REGISTRATION: Sequential Nephron Blockade vs. Dual Blockade Renin-angiotensin System + Bisoprolol in Resistant Arterial Hypertension (ResHypOT). ClinicalTrials.gov, ID: NCT02832973 . Registered on 14 July 2016. First received: 12 June 2016. Last updated: 18 July 2016.