| Objective:This study is to evaluate the therapeutic efficacy and safety ofspironolactone by comparing antihypertensive effect in groups of amlodipine,perindopril and hydrochlorothiazide with or without spironolactone in thetreatment of refractory hypertension (RH), and to discuss the mechanism ofspironolactone in the treatment of RH.Methods:In this experiment we choose120cases with RH admitted in our hospitalwith58male and62female,aged33~84years old and43~92years oldrespectively.Patients were randomly divided into the experimental group andthe control groups with60cases respectively. The experimental group isadministrated with spironolactone20mg/d, amlodipine5mg/d, perindopril4mg/d, and hydrochlorothiazide25mg/d; the control group with amlodipine5mg/d, perindopril4mg/d, hydrochlorothiazide25mg/d. Five patients wasexited because they refused to do the related inspection. The treatments of theothers lasted for eight weeks.In this eight-weeks time, no otherantihypertensive medications, smoking, drinking, caffeine, liquorice andephedra are allowed.24-hour ambulatory blood pressure monitoring (ABPM)is executed at0weeks,2weeks,4weeks,8weeks after treatment, in order toobtain the mean24-hour systolic blood pressure (SBP) and diastolic bloodpressure (DBP), pulse pressure (PP)=SBP-DBP. Liver function, kidneyfunction, serum uric acid, serum electrolyte and other safety index wasmeasured periodically. Adverse events were recorded too. The experimentaldata was presented as mean±standard deviation.Statistical analyses wereperformed with SPSS13.0.T-test, ANOVA and chi-square test was used to check differences. P<0.05was considered statistically significant.Results:1The comparison of clinical data:There are no significant differences between the experimental group andthe control group in gender, age, PRA and other clinical data (P>0.05).2Changes of BP in the experimental group:2.1SBP: At the0,2nd and4th week after treatment, SBP droppedgradually from164.8±9.3mmHg to144.0±4.4mmHg, and all of them hadsignificant differences (P <0.05); SBP dropped to143.5±4.5mmHg at the8thweek, but the SBP of4th week to8th week did not change significantly(P>0.05).2.2DBP: At the0,2nd and4th week after treatment, DBP droppedgradually from93.8±8.1mmHg to84.3±7.7mmHg, and all of them hadsignificant differences (P <0.05); DBP dropped to84.2±7.9mmHg at the8thweek, but the DBP of4th week to8th week did not change significantly(P>0.05).2.3PP: At the0,2nd and4th week after treatment, PP dropped graduallyfrom71.0±11.7mmHg to59.7±8.4mmHg, and all of them had significantdifferences (P <0.05); PP dropped to59.3±8.8mmHg at the8th week, but theDBP of4th week to8th week did not change significantly(P>0.05).3Changes of BP in the control group:3.1SBP: At the0,2nd and4th week after treatment, SBP droppedgradually from165.8±7.7mmHg to156.1±3.5mmHg, and all of them hadsignificant differences (P <0.05); SBP rised to156.2±3.5mmHg at the8thweek, but the SBP of4th week to8th week did not change significantly(P>0.05).3.2DBP: At the0and2nd week after treatment, DBP dropped from91.0±7.4mmHg to86.4±7.5mmHg, and the difference was significant (P <0.05). At the2nd,4th and8th week after treatment, DBP dropped graduallyfrom86.4±7.5mmHg to85.9±8.0mmHg, but they had no significantdifference (P>0.05). 3.3PP: At the0and2nd week after treatment, PP dropped from74.8±10.0mmHg to73.8±8.0mmHg, and the difference was insignificant (P>0.05). PP dropped to69.9±7.9mmHg at the4th week, and it had significantdifference between the PP of2nd week and4th week (P <0.05). PP rised to70.2±8.2mmHg at the8th week, but the PP of4th week to8th week did notchange significantly(P>0.05).4The descending of BP of the two groups:4.1SBP drop: At the2nd,4th and8th week after treatment, the drops ofSBP in experimental group were significantly higher than in control group (P<0.05).4.2DBP drop: At the2nd,4th and8th week after treatment, the drops ofDBP in experimental group were higher than in control group. The maineffects of the two groups had no significant difference(P>0.05), but theinteraction was significant(P <0.05).4.3PP drop: At the2nd,4th and8th week after treatment, the drops of PPin experimental group were significantly higher than in control group (P <0.05).4.4Effective rate: The effective rate of experimental group was73.68%,and the effective rate of control group was43.10%, and the difference wassignificant (P <0.05).5The influence of plasma renin activity (PRA) status:5.1In low (L), middle (M) and high(H) PRA groups, no matter whichgroup, the level of PRA and plasma aldosterone (Ald.) had no significantdifference between experimental group and control group (P>0.05).5.2SBP drop at the8th week after treatment: In different PRA groups,the drops of SBP in experimental group were significantly higher than incontrol group (P <0.05).5.3DBP drop at the8th week after treatment: In different PRA groups,the drops of DBP in experimental group were higher than in control group.The main effects of the two groups had no significant difference(P>0.05), butthe interaction was significant(P <0.05). 5.4PP drop at the8th week after treatment: In different PRA groups, thedrops of PP in experimental group were higher than in control group.In the LPRA group, the main effects had no significant difference(P>0.05), but theinteraction was significant(P <0.05). The difference of drops was significantin M PRA group (P <0.05),but it was insignificant in H PRA group (P>0.05).6Safety index:Two patients in the control group got hypokalemia, but had returned tonormal after corresponding treatment. One male patient in the experimentalgroup got breast pain, but tolerated, and had improved gradually. Threepatients in two groups got dry cough, but tolerated, and had improvedgradually. The liver function, kidney function, serum uric acid, serumelectrolyte and other safety index of other patients had no significant change.Hyperkalaemia, male breasts hyperplasia and other adverse events were notobserved.Conclusion:The application of additional aldosterone antagonist-spironolactone isable to reduce SBP, DBP and PP of patients with RH significantly, and toimprove the control rate significantly, the mechanisms of which are decliningwater-sodium retention, improving aldosterone escape, mitigating insulinresistance and so on. Spironolactone is active in all PRA status of RH. Smalldoses of spironolactone has light side effects, high safety, tolerability, andcurative effect, is suitable for all PRA status of RH, and maybe improve theprognosis of patients with RH. The results of the study indicate thatspironolactone is a effective clinical drug for the treatment of RH. |
PDF Full Text Request