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.
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.
3.
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.