Effects of different antihypertensive drug classes on central and ambulatory blood pressure in resistant hypertension: A randomized clinical trial

This study compares sequential nephron blockade (SNB) and renin-angiotensin system sequential blockade (RASSB) in patients with resistant hypertension (RHTN), evaluating central systolic pressure, arterial stiffness, pulse pressure (PP) and ambulatory blood pressure monitoring (ABPM). Seventy-two RHTN patients were randomly assigned to SNB (n = 35, 22 females, 13 males) or RASSB (n = 37, 22 females, 15 males). SNB included multiple diuretics (furosemide, spironolactone, hydrochlorothiazide) to enhance natriuresis and counter intra-renal compensatory mechanisms. RASSB employed stepwise renin-angiotensin system blockade using lisinopril, bisoprolol and losartan, even in patients already on valsartan. Office blood pressure reductions were significant in both groups (P < 0.0001). SNB: systolic blood pressure (SBP) from 174.5 to 127.0 mmHg, diastolic blood pressure (DBP) from 105.3 to 78.11 mmHg. SBP from 178.4 to 134.4 mmHg, DBP from 102.7 to 77.33 mmHg. ABPM confirmed 24-h reductions (P < 0.0001). SNB showed greater PP reduction (Δ = 22.99 vs 15.93 mmHg, P = 0.024) and central systolic pressure reduction (Δ = -10.3 vs -5.1 mmHg, P = 0.036). RASSB produced a pronounced heart rate decrease (Δ = -12.4 beats per minute, P < 0.0001). No treatment-related discontinuations occurred. SNB demonstrated superior efficacy in reducing central SBP and PP, while RASSB more effectively lowered heart rate. These distinct hemodynamic responses support individualized treatment strategies for patients with RHTN. gov identifier: NCT02832973.