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

OBJECTIVES: We assessed the influence of medication adherence on blood pressure (BP) control and target organ damage in a pre-specified analysis of a published trial comparing sequential nephron blockade (SNB) or sequential renin-angiotensin system blockade (SRASB) in patients with resistant hypertension. METHODS: Patients were randomized to SNB (n = 82) or SRASB (n = 82) and studied at baseline and after 12 weeks. BP was measured by ambulatory blood pressure monitoring. Carotid-femoral pulse wave velocity (PWV) was measured by applanation tonometry and left ventricular mass (LVM) by echocardiography. Low medication adherence was assessed through plasma irbesartan concentration below 20 ng/ml; urinary N-acetyl-seryl-aspartyl-lysyl-proline/creatinine ratio below 4 nmol/mmol; last medication intake before visit greater than 24 h and pill counting below 80% of theoretical intake. Medication adherence score (sum of items, max = 4) is defined as low (medication adherence score <2) or acceptable (medication adherence score ≥2). RESULTS: Among 164 patients, 134 (81.7%) had acceptable medication adherence and 30 (18.3%) low medication adherence, with similar proportions in the SNB and SRASB arms. After 12 weeks, in patients with acceptable medication adherence, BP was more frequently controlled in those treated with SNB (64%), than SRASB (18%; P < 0.001). The difference in daytime SBP was -11.5 mmHg 95% confidence interval (CI) -15.4 to -7.5, P < 0.0001 in patients with acceptable medication adherence. In contrast, in patients with low medication adherence, the difference between groups was smaller and not significant (-9.4 mmHg, 95% CI -20.4 to 1.7, P = 0.09). Independently of BP changes, PWV and LVM decreased more in the SNB than in the SRASB arm when medication adherence was acceptable (-0.52 m/s, 95% CI -1.3 to -0.007, P = 0.047; and -24 g/m, 95% CI -36 to -12, P = 0.0003), whereas no significant changes were observed in low medication adherence patients. CONCLUSION: Medication adherence contributes to BP-lowering and regression of target organ damage. The differential effects of SNB and SRASB is observed in patients with acceptable medication adherence, and not in patients with low medication adherence.