0272: True antihypertensive efficacy of sequential nephron blockade in patients with resistant hypertension and confirmed medication adherence

Abstract

We previously showed (Bobrie et al. J Hypertens 2012) that sequential-nephron blockade (SNB) was more effective than combined renin angiotensin system blockade (RB) for controlling BP in patients with resistant hypertension (RH). In this post-hoc analysis, we assessed medication adherence (MA) and its influence on the antihypertensive response to SNB/RB with a new combined scoring system. Pts with daytime ambulatory SBP/DBP (dASBP/dADBP) >135 and/or 85 mmHg, despite 4 week-treatment with irbesartan 300 mg+HCTZ 12.5 mg+amlodipine 5 mg, were randomised either to SNB (i.e.+spironolactone 25 mg, then +furosemide 20-40 mg, then +amiloride 5 mg, n=82) or RB (ramipril 5-10 mg, then bisoprolol 5-10 mg, RB group, n=82) for 12 weeks. MA was scored according to 4 criteria: (i) trough/peak plasma irbesartan (Irb) concentration (HPLC); (ii) urinary AcSDKP/creatinine ratio (UR) to evaluate ramipril intake; (iii) delay of last medication intake before visit (LMI); and (iv) pill counting (PC, %). One point of MA score was attributed to trough Irb >20ng/ml, UR >4nmol/mmol, LMI <24h and PC >80%. MA was defined as low (LMA, score <2), intermediate (IMA, score=3), and optimal (OMA, score=4). 82 pts among 164 had OMA (46 SNB and 36 RB); 52 pts had IMA (23 SNB and 29 RB); and 30 pts had LMA (13 SNB and 17 RB) (inter-groups difference: NS). LMA pts were younger than SMA pts (50±11 vs. 56±10 yrs, p<0.011). In OMA pts, the difference in dASBP/dADBP between SNB vs RB was significant (–11 [–17;–6]/–6 [–9;–2] mmHg, p<0.0001/p=0.0025), favoring SNB, whereas in LMA pts the significant difference between the two groups was no more observed (–6 [–19;7]/–1 [–10;7] mmHg, p=0.352/p=0.7096). The major BP lowering effect of SNB vs. RB observed in pts with OMA is lost in pts LMA. Combined methods for assessing MA allow determining the true efficacy of antihypertensive strategies in patients with RH. Reinforcement of MA in RH pts is deemed necessary.