Observation On The Efficacy And Safety Of Buzhong Yiqi Pill Combined With Midodrine In Symptomatic Neurogenic Orthostatic Hypotension

Background and purposeNeurogenic orthostatic hypotension(n OH)is a typical manifestation of a sustained decrease in blood pressure in the standing position caused by autonomic nervous failure(sympathetic innervation vasoconstriction).There is no relevant evidence-based guideline for the diagnosis and treatment of the disease all over the world.At present,the Food and Drug Administration(FDA)in U.S.only approves midodrine and droxidopa as standard drugs for n OH.However,their efficacy and safety are still controversial in some studies,and there is no comprehensive study on the longterm use of these drugs.Therefore,the exploration of a more perfect drug treatment scheme is of great significance to the current research in the field of n OH,but also in line with the spirit of the latest expert consensus.Some studies suggest that Buzhong Yiqi decoction may have the effect of improving dizziness and syncope,and one of the main symptoms of n OH patients is dizziness and/or syncope.Therefore,it is necessary to study the exact curative effect of Buzhong Yiqi Pill combined with midodrine hydrochloride in n OH patients.At the same time,it is also very important to study the safety of the combination therapy as study on the pharmacological mechanism of traditional Chinese medicine is rather lags behind.Materials and MethodsThe clinical data of 36 patients with n OH were collected.According to random number table method,patients were randomly assigned to test group and control group in a 2:1 ratio.Among them,24 were in the experimental group and 12 in the control group.Test group: Buzhong Yiqi Pills(Zhongjing Wanxi,6g/bag),1 bag,1 time,3 times a day(before morning,before lunch and after afternoon)combined with Midodrine Hydrochloride tablets(Miwei,2.5mg),1 tablet once,2 times a day(before morning,before lunch).Control group: Midodrine hydrochloride tablets(Miwei,2.5 mg),1 tablet once a time,2 times a day(before morning,before lunch).At the hospital baseline,we obtain a medical history,perform physical examination(complete the blood routine examination,urine routine examination,excrement routine examination,liver function,renal function,electrolytes,blood sugar,thyroid hormone,vitamin B12,cardiac ultrasound,electrocardiogram,head MRI,24 h dynamic electrocardiogram and ambulatory blood pressure examination),and conducted self-reported questionnaires(OHQ and PHQ-9 Depression Screening Scale).After resting for 10 minutes in the supine position,supine blood pressure(BP)and heart rate(HR)were measured,and BP and HR were measured after standing,1 minute,and 3 minutes,respectively.The maximum decrease in systolic blood pressure(SBP)and diastolic blood pressure(DBP)within 3 min after standing was recorded.Follow-up observation was performed 2 weeks and 1 month after the start of treatment.We also conduct standing blood pressure measurement,heart rate measurement and questionnaire survey.Drugs compliance,possible side effects and related drugs(drugs that affect the autonomic nervous system and blood pressure were discouraged during the trial)were checked.All blood pressure measures were taken 2.5 hours after breakfast to avoid postprandial hemodynamic effects.Primary endpoint: The improvement of OHQ questionnaire scores was evaluated at 1 month after the treatment cycle.Secondary endpoints:(1)Percentage of patients who met the n OH blood pressure criteria at 2 weeks and 1 month after treatment;(2)Improvement in blood pressure reduction at 1 month after treatment(compared to the maximum decrease in SBP and DBP within 3 min after supine position in the supine position).The safety endpoint is adverse events.(3)The improvement of PHQ-9 questionnaire scores was evaluated at 1 month after the treatment cycle.An adverse event is defined as any unexpected response that is considered to be related to the treatment,and the causal relationship is determined by the treating physician.ResultsThe primary endpoint: After a one-month treatment of 36 nOH patients in the control and experimental groups,the OHQ scores of the two groups were significantly lower than those at the time of admission.The comparison between the groups suggested that the experimental group was superior to the control group(U=-2.438,p=0.015).Specific to the OHSA and OHDAS scores of the sub-tables,the test group also showed significant advantages(U=-2.128,p=0.033;U=-2.233,p=0.026).Secondary endpoints:(1)After 2 weeks of treatment,37.5% of the patients in the experimental group still met the diagnostic criteria for n OH blood pressure,and 41.7% in the control group.There was no statistical difference between the two groups(p>0.05).After 1 month of treatment,the percentage of people that met the diagnostic criteria for n OH blood pressure in test group and the control group were 29.2% and 33.3%,respectively.There was no statistical difference between the two groups(p>0.05).(2)The degree of decline in SBP and DBP in both groups was significantly improved compared with the baseline at hospital admission at 1 month after treatment(p<0.01).However,there was no statistical difference between the groups(t=-1.149,p=0.259;t=-0.620,p=0.539).(3)In the PHQ-9 score,the two groups did not show statistical difference at 1 month after treatment(t=0.502,p=0.619).The adverse reactions in both groups were mild to moderate events.The incidence of the test group was 12.5%,and that of the control group was 16.7%.There was no statistical difference between the two groups(p=0.640).Conclusion(1)In the treatment for one month,Symptomatic n OH patients treated with Buzhong Yiqi Pill combined with midodrine hydrochloride regimen,had significantly better performance than the single group in total score of OHQ questionnaire,the symptom score and subscale score of daily activity.Meanwhile,the combination treatment group did not show a significant advantage compared with the midodrine hydrochloride group in depression score,the percentage of participants met diagnostic criteria for n OH blood pressure and the improvement in blood pressure reduction.However,according to the spirit of the latest expert consensus,the effectiveness of the combination regimen can be recognized.(2)Regarding the safety of the combination treatment,no significant increase in the number and severity of adverse events was observed during our one-month followup study.