Kjeldsen Sverre E, Cha Gloria, Villa Giuseppe, Mancia Giuseppe
Oslo University Hospital Ullevaal, University of Oslo, Oslo, Norway.
KRK Medical Research Institute, Dallas, Texas, USA.
J Clin Pharmacol. 2016 Sep;56(9):1120-9. doi: 10.1002/jcph.712. Epub 2016 Mar 7.
DISTINCT was an 8-week, double-blind, randomized study to investigate the antihypertensive efficacy and safety of various nifedipine gastrointestinal treatment system (GITS)/candesartan cilexetil (N/C) dose combinations, vs respective monotherapies or placebo, in patients with diastolic blood pressure (DBP) ≥95 to <110 mm Hg. The current prespecified analysis compared BP reduction in participants with mild vs moderate baseline hypertension (ie, systolic [S]BP <160 mm Hg vs ≥160 mm Hg and DBP <100 mm Hg vs ≥100 mm Hg). A total of 1362 patients were analyzed by descriptive statistics. In all patient subgroups investigated, the NC combinations (ie, N: 20, 30, or 60 mg; C: 4, 8, 16, or 32 mg daily) provided greater SBP and DBP lowering and higher rates of BP control (defined as BP <140/90 mm Hg) than respective monotherapies or placebo, with greatest absolute BP reductions observed in the moderately elevated SBP or DBP subgroups. A trend to dose-response relationship was observed in each subgroup. In each SBP and DBP subgroup, treatment-related vasodilatory events (flushing, headache, or edema) were less frequent for patients receiving NC combination therapy than N monotherapy. These analyses support the use of calcium antagonist and angiotensin receptor blocker combination therapy in patients with both mild and moderate hypertension, for whom effective BP normalization and good drug tolerance would greatly reduce the risk of cardiovascular events.
DISTINCT是一项为期8周的双盲随机研究,旨在调查不同硝苯地平胃肠道治疗系统(GITS)/坎地沙坦酯(N/C)剂量组合相对于各自单一疗法或安慰剂,在舒张压(DBP)≥95至<110 mmHg患者中的降压疗效和安全性。当前的预先设定分析比较了轻度与中度基线高血压患者(即收缩压[S]BP<160 mmHg与≥160 mmHg,舒张压DBP<100 mmHg与≥100 mmHg)的血压降低情况。通过描述性统计分析了总共1362例患者。在所有研究的患者亚组中,NC组合(即N:20、30或60 mg;C:每日4、8、16或32 mg)比各自的单一疗法或安慰剂能更大程度地降低收缩压和舒张压,并具有更高的血压控制率(定义为血压<140/90 mmHg),在收缩压或舒张压中度升高的亚组中观察到最大的绝对血压降低。在每个亚组中均观察到剂量反应关系趋势。在每个收缩压和舒张压亚组中,接受NC联合治疗的患者与硝苯地平单一疗法相比,治疗相关的血管舒张事件(潮红、头痛或水肿)发生频率更低。这些分析支持在轻度和中度高血压患者中使用钙拮抗剂和血管紧张素受体阻滞剂联合治疗,对于这些患者,有效的血压正常化和良好的药物耐受性将大大降低心血管事件的风险。