Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Am J Hypertens. 2013 Dec;26(12):1381-8. doi: 10.1093/ajh/hpt105.
Recently, we reported that transient treatment of genetically hypertensive rats with high-dose angiotensin receptor blocker (ARB) causes regression of established hypertension. In this study, we investigated whether treatment with candesartan or nifedipine controlled-release (CR) resulted in a sustained regression of hypertension in humans.
Patients aged 30 to 59 years with untreated stage 1 essential hypertension and a family history of hypertension were treated with the antihypertensive agents candesartan (n = 124) or nifedipine CR (n = 120). After 1 year of treatment (phase 1), the medications were tapered and discontinued (phase 2). During phase 2, home and office blood pressures were monitored for another year to assess posttreatment reoccurrence of stage 1 hypertension.
In phase 1, after 1 year of treatment a similarly substantial BP decrease was seen in the candesartan (-24.5/16.1 mm Hg) and nifedipine (-26.8/18.0 mm Hg) groups. In phase 2 there was a substantial reoccurrence of hypertension; at the study end, only 1 patient was able to continue without antihypertensive medication. However, a Kaplan-Meier analysis revealed a significant delay of reoccurrence of hyper tension (P = 0.0001) in the candesartan group.
One year of treatment with candesartan or nifedipine CR was not associated with marked regression of hypertension in humans at the standard doses used in this trial. However, withdrawal of candesartan was associated with a slightly longer delay before restarting medications. Further studies with larger doses of candesartan given over a longer time are required to determine whether such a regimen may induce sustainable and clinically relevant reversal of hypertension and alteration in its natural history.
最近,我们报道了在遗传高血压大鼠中短暂给予大剂量血管紧张素受体阻滞剂(ARB)治疗可导致已确立的高血压消退。在这项研究中,我们研究了坎地沙坦或硝苯地平控释(CR)治疗是否会导致人类高血压的持续消退。
年龄在 30 至 59 岁之间、未经治疗的 1 期原发性高血压且有高血压家族史的患者,接受降压药物坎地沙坦(n = 124)或硝苯地平 CR(n = 120)治疗。治疗 1 年后(第 1 阶段),逐渐减少并停止药物治疗(第 2 阶段)。在第 2 阶段,再监测 1 年家庭和办公室血压,以评估治疗后 1 期高血压的再次发生。
第 1 阶段,坎地沙坦组(-24.5/16.1mmHg)和硝苯地平 CR 组(-26.8/18.0mmHg)在治疗 1 年后血压同样显著下降。在第 2 阶段,高血压有很大程度的再次发生;研究结束时,只有 1 例患者能够继续不服用降压药物。然而,Kaplan-Meier 分析显示坎地沙坦组高血压再次发生的时间明显延迟(P = 0.0001)。
在本试验使用的标准剂量下,坎地沙坦或硝苯地平 CR 治疗 1 年与人类高血压的明显消退无关。然而,坎地沙坦停药后重新开始用药的时间略有延长。需要进一步进行更大剂量坎地沙坦治疗时间更长的研究,以确定这种治疗方案是否可诱导高血压的持续和临床相关逆转以及其自然史的改变。