1.
Fixed-combination of amlodipine and diuretic chronotherapy in the treatment of essential hypertension: improved blood pressure control with bedtime dosing-a multicenter, open-label randomized study.
Zeng, J, Jia, M, Ran, H, Tang, H, Zhang, Y, Zhang, J, Wang, X, Wang, H, Yang, C, Zeng, C
Hypertension research : official journal of the Japanese Society of Hypertension. 2011;(6):767-72
Abstract
Previous studies have demonstrated that individual anti-hypertension medications have different effects when administered in the morning vs. the evening. However, the impact of administration timing on fixed combinations of anti-hypertensive medications on blood pressure control is still unknown. In the present study, we examined the administration time-dependent effects of a fixed combination of amlodipine and diuretics (amlodipine complex) on blood pressure in hypertensive subjects. Eighty patients from Chongqing City were enrolled in this study. Subjects were randomly assigned to receive a single pill (amlodipine complex, each tablet containing amlodipine 5 mg and hydrochlorothiazide 25 mg), either in the morning (0800 hours, n=40) or at bedtime (2200 hours, n=40). Blood pressure was measured by ambulatory monitoring every 20 min during the day and every 30 min at night for 24 consecutive hours before and after the 12 weeks of treatment. Following treatment, the 24-h mean systolic and diastolic blood pressures were reduced significantly in both the morning and bedtime groups. However, the morning blood pressure surge was reduced to a greater degree in the bedtime group. In addition, the nocturnal blood pressure and the 24 h mean blood pressure were lower in the bedtime group. More patients converted from having a non-dipper to dipper blood pressure in the bedtime group. These findings confirm that amlodipine complexes have different efficiencies depending on treatment time. Administration of amlodipine complexes at bedtime could optimize the anti-hypertensive effect by augmenting blood pressure-lowering effects, increasing the diurnal/nocturnal ratio of blood pressure, normalizing the blood pressure pattern and minimizing the morning blood pressure surge.
2.
Antihypertensive efficacy and tolerability of aliskiren/hydrochlorothiazide (HCT) single-pill combinations in patients who are non-responsive to HCT 25 mg alone.
Blumenstein, M, Romaszko, J, Calderón, A, Andersen, K, Ibram, G, Liu, Z, Zhang, J
Current medical research and opinion. 2009;(4):903-10
Abstract
OBJECTIVE Thiazide diuretics such as hydrochlorothiazide (HCT) are a widely used first-line treatment for hypertension, but most patients will not achieve blood pressure (BP) control with HCT alone and so will require combination therapy. In this study the efficacy, safety and tolerability of a single-pill combination (SPC) of the direct renin inhibitor aliskiren with HCT were investigated in patients non-responsive to HCT 25 mg therapy. METHODS In this study, 722 patients with hypertension and an inadequate response to 4 weeks of HCT 25 mg (mean sitting diastolic BP > or =90 and <110 mmHg) were randomized to once-daily, double-blind treatment for 8 weeks with an SPC of aliskiren/HCT 300/25 mg or 150/25 mg, or continued HCT 25 mg monotherapy. Least-squares mean changes in mean sitting systolic/diastolic BP (msSBP/DBP) from double-blind baseline were analyzed for the ITT population at week 8 endpoint. RESULTS Aliskiren/HCT 300/25 mg and 150/25 mg SPCs lowered msSBP/DBP from baseline by 16.7/10.7 and 12.9/8.5 mmHg, respectively, both significantly greater reductions than HCT 25 mg alone (7.1/4.8 mmHg; both p < 0.001). Rates of BP control (<140/90 mmHg) were also significantly higher with aliskiren/HCT 300/25 mg (58%) and 150/25 mg (49%) than with HCT (26%; both p < 0.001). Aliskiren/HCT 300/25 mg provided significantly greater msSBP/DBP reductions and rates of BP control than the 150/25 mg SPC dose (all p < 0.05). Aliskiren/HCT SPC treatment showed similar tolerability to HCT alone and a numerically lower incidence of hypokalemia (serum potassium <3.5 mmol/L; aliskiren/HCT, 1.3-2.2%: HCT alone, 3.4%). CONCLUSION Aliskiren/HCT SPCs provide clinically significant BP reductions and improved BP control rates in patients who are non-responsive to HCT 25 mg monotherapy. Limitations of the study were the mainly Caucasian patient population and the non-responder design.