1.
Association of the use of amlodipine with clopidogrel response in Chinese patients undergoing percutaneous coronary intervention.
Liu, XQ, Lin, S, Qiu, LL, Lin, L, Zhao, YY, Xu, HM, Zhang, J, Zou, JJ
Die Pharmazie. 2014;(11):814-7
Abstract
Until recently, the precise mechanism of clopidogrel resistance remains unclear. Some clinical studies have demonstrated that calcium channel blockers (CCBs) could reduce the antiplatelet effect of clopidogrel in white or black subjects, implicating in clopidogrel resistance. However, that remains to be determined in Chinese patients. In this study, we sought to determine whether there could be a decreased antiplatelet effect of clopidogrel and an increased risk for developing adverse cardiovascular events after concomitant use of different CCBs and clopidogrel in Chinese patients treated with percutaneous coronary intervention (PCI). A subcohort of 249 patients not carrying the CYP2C19 *2, *3 or *17 variant was identified from a total of 617 consecutive clopidogrel-treated patients undergoing PCI and then categorized into three groups according to various CCB treatments. Baseline data, clinical characteristics and blood samples were collected for all patients. The maximum platelet aggregation (MPA) was measured by light transmittance aggregometry (LTA) to assess the platelet function in blood samples obtained from patients on day 3 after starting daily clopidogrel maintenance doses. The primary clinical end-point was a definite stent thrombosis (ST) episode, whereas secondary end-points were other major adverse cardiovascular events within 12 months after stenting. Of the 249 patients not carrying CYP2C19 *2, *3 and *17 variants, the ADP-induced MPA differed significantly among the three groups (P < 0.001). The MPA values were 1.76 times in the amlodipine group (41.6 ± 23.0%) than in the No CCB group (23.7 ± 14.1%) (P < 0.001). Moreover, in a linear regression model, the use of amlodipine was independently associated with MPA values (R = 0.375, P < 0.001), suggesting that the use of amlodipine might link to the increased MPA. However, the incidence of 1-year ST was not significantly higher in the amlodipine group than the No CCB group (OR, 4.80; 95% CI, 0.87 to 26.52; P = 0.068), and none of the risks for other adverse cardiovascular events were significantly different across the three groups (P = 0.11).
2.
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.
3.
Aliskiren and the calcium channel blocker amlodipine combination as an initial treatment strategy for hypertension control (ACCELERATE): a randomised, parallel-group trial.
Brown, MJ, McInnes, GT, Papst, CC, Zhang, J, MacDonald, TM
Lancet (London, England). 2011;(9762):312-20
Abstract
BACKGROUND Short-term studies have suggested that the use of initial combination therapy for the control of blood pressure improves early effectiveness. We tested whether a combination of aliskiren and amlodipine is superior to each monotherapy in early control of blood pressure without excess of adverse events, and if initial control by monotherapy impairs subsequent control by combination therapy. METHODS We did a double-blind, randomised, parallel-group, superiority trial at 146 primary and secondary care sites in ten countries, with enrolment from Nov 28, 2008, to July 15, 2009. Patients eligible for enrolment had essential hypertension, were aged 18 years or older, and had systolic blood pressure between 150 and 180 mm Hg. Patients were randomly assigned (1:1:2) to treatment with 150 mg aliskiren plus placebo, 5 mg amlodipine plus placebo, or 150 mg aliskiren plus 5 mg amlodipine. Random assignment was through a central interactive voice response system and treatment allocation was masked from the patients. From 16-32 weeks, all patients received combination therapy with 300 mg aliskiren plus 10 mg amlodipine. Our primary endpoints, assessed on an intention-to-treat basis (ie, in patients who received the allocated treatment), were the adjusted mean reduction in systolic blood pressure from baseline over 8 to 24 weeks, and then the final reduction at 24 weeks. This trial is registered with ClinicalTrials.gov, number NCT00797862. FINDINGS 318 patients were randomly assigned to aliskiren, 316 to amlodipine, and 620 to aliskiren plus amlodipine. 315 patients initially allocated to aliskiren, 315 allocated to amlodipine, and 617 allocated to aliskiren plus amlodipine were available for analysis. Patients given initial combination therapy had a 6·5 mm Hg (95% CI 5·3 to 7·7) greater reduction in mean systolic blood pressure than the monotherapy groups (p<0·0001). At 24 weeks, when all patients were on combination treatment, the difference was 1·4 mm Hg (95% CI -0·05 to 2·9; p=0·059). Adverse events caused withdrawal of 85 patients (14%) from the initial aliskiren plus amlodipine group, 45 (14%) from the aliskiren group, and 58 (18%) from the amlodipine group. Adverse events were peripheral oedema, hypotension, or orthostatic hypotension. INTERPRETATION We believe that routine initial reduction in blood pressure (>150 mm Hg) with a combination such as aliskiren plus amlodipine can be recommended. FUNDING Novartis Pharma AG.