小剂量螺内酯治疗顽固性高血压的临床研究

Effects and influence factors of low-dose spironolactone in patients with resistant hypertension

目的评价常规联合用药加用小剂量螺内酯治疗顽固性高血压的有效性和安全性,并研究血钾和ARR对螺内酯治疗反应性的影响。方法将符合纳入标准的164例顽固性高血压患者随机分为螺内酯组(观察组)和安慰剂组(对照组),每组各82例。两组在原治疗方案的基础上分别加用螺内酯20mg/d和安慰剂。随访3个月,观测血压、血钠、血钾、血肌酐和血糖等指标的变化。结果除螺内酯组有4例患者因明显不良反应而退出试验外,其余160例患者均完成随访。螺内酯治疗3个月后,收缩压、舒张压和脉压的降幅分别达到-13.4(-17.7,-8.3)mm Hg、-5.8(-7.3,-3.4)mm Hg和-8.1(-11.9,-2.8)mm Hg,与安慰剂相比具有显著的统计学差异(P均<0.01)。螺内酯导致血钾和血肌酐升高,以及轻微的血钠降低(P均<0.01),但均在可控范围之内。螺内酯对血糖无影响(P=0.804)。此外基线血钾≤4.1mmol/L的亚组或基线ARR≥141.5的亚组,在经螺内酯治疗3个月后,收缩压和舒张压下降幅度更大(P均<0.01)。结论顽固性高血压患者加用小剂量螺内酯能有效降低收缩压和舒张压,且不良反应发生率低,耐受性好,同时基线血钾和ARR能有效预测螺内酯治疗的反应性。

Objective To assess the effect and safety of conventional combination therapy with the addition of low-dose spironolactone in resistant hypertension and discuss the influence of serum potassium and ARR on the therapeutic effect of spironolactone. Methods 164 patients with resistant hypertension met the inclusion criteria were randomly divided into spirono-lactone group （observation group） and placebo group （control group）,each of them includes 82 patients. On the basis of previous therapeutic regimen,patients in each group receive spironolactone at a dose of 20mg once daily or a placebo once daily,respec-tively. During the follow-up period of 3 month,the changes of blood pressure,serum sodium,potassium,creatinine and glycemia were measured. Results Except 4 patients in the spironolactone group dropping out of the trial due to adverse events,all the oter patients completed the study. After 3 month of spironolactone treatment,the fall of SBP,DBP and pulse pressure was-13.4（-17.7,-8.3）mmHg,-5.8（-7.3,-3.4）mmHg and -8.1（-11.9,-2.8）mmHg,respectively. Compared with placebo,the difference was statisti-cally significant（P〈0.01 for all）. Spironolactone led to significant increases of serum potassium and creatinine,and a small but sig-nificant decrease of serum sodium （P〈0.01 for all）,and all the changes were under control. Spironolactone had no effect on blood glucose （P=0.804）. Moreover,after 3 month of spironolactone treatment,patients with baseline potassium ≤4.1mmol/L or baseline ARR≥141.5 showed larger SBP and DBP reduction （P〈0.01 for all）. Conclusion The addition of low-dose spironolactone in pa-tients with resistant arterial hypertension leads to a significant decrease of both SBP and DBP with low incidence of adverse clini-cal consequences and good tolerance. In addition,both baseline potassium ≤4.1mmol/L and ARR≥141.5 predicted larger SBP and DBP reduction with spironolactone treatment after 3 months.