Effectiveness of Zhuling decoction on diuretic resistance in patients with heart failure: a randomized, controlled trial

Abstract

Objective: To test the effects of Zhuling decoction on patients with diuretic resistance in heart failure compared with a group of patients undergoing conventional treatment alone.

Methods: This research was a prospective, randomized, controlled study. From July 2018 to August 2020, 96 diuretic resistance patients from the Cardiovascular Research Center of Taicang Hospital affiliated with Nanjing University of Traditional Chinese Medicine (Grade III Hospital of Traditional Chinese Medicine) were enrolled in the study. The subjects were randomly divided into an observation group (48 cases) and a control group (48 cases). Patients in both groups received conventional treatment. In addition, observation group patients received Traditional Chinese Medicine Zhuling decoction. The primary endpoint was the urine output mean difference between Day 1 and Day 7 after treatment. Secondary endpoints were the changes over time in the N-terminal pro-B type natriuretic peptide (NT-proBNP), New York Heart Association (NYHA) functional classification, and Minnesota Living with Heart Failure Questionnaire (MLHFQ). The safety and tolerability of the drug were comprehensively evaluated based on adverse drug reactions, as well as laboratory-assisted tests for liver and kidney function and electrolytes.

Results: Significant improvements were demonstrated for urine output in the two groups at Day 7, with a 1325 1045 mL difference in favor of the observation group ( = 0.018). The observation group also had greater improvements in NT-proBNP and NYHA functional classification changes than the control group. At the 30th day of follow-up, a significant reduction in negative findings on the MLHFQ from baseline was observed in both groups, but the observation group demonstrated a significantly greater reduction than the control group ( <0.001).

Conclusions: Zhuling decoction could be used in combination therapy for patients with diuretic resistance in heart failure in addition to standard treatment.

Keywords: Zhuling decoction; diuretic resistance; heart failure; randomized controlled trial; treatment outcome; urine output.

Figure 1. Study design

CO: control group; OB: observation group; NT-proBNP: N-terminal pro-B type natriuretic peptide; NYHA: New York Heart Association; MLHFQ: Minnesota Living with Heart Failure Questionnaire.

Figure 2. Trend of urine volume according to group

On the x-axis, the change in time, and on the y-axis, the record of urine output of patients. The CO group routinely treated with albumin, dopamine, hydrochlorothiazide and other drugs. The OB group received Zhuling decoction for at least 7 d on the basis of CO group. With prolonged treatment time, the urine volume in both groups increased significantly, and the increase was more significant in the OB group (P = 0.018). CO: control group (n = 48); OB: observation group (n = 48).

Figure 3. Changes in NT-proBNP before and after treatment in the 2 groups

The CO group routinely treated with albumin, dopamine, hydrochlorothiazide and other drugs. The OB group received Zhuling decoction for at least 7 d on the basis of CO group. The median NT-proBNP was 8060 ng/L pretreatment and 4000 ng/L posttreatment in the OB group. Those in the CO group were 5690 and 4945 ng/L, respectively. NT-proBNP improved in both groups, with a greater improvement in the OB group (P < 0.001). NT-proBNP: N-terminal pro-B type natriuretic peptide. CO: control group (n = 48); OB: observation group (n = 48).

Figure 4. Changes in MLHFQ before and after treatment in the 2 groups

The treatment measures of the two groups were as mentioned above. All subjects received the first MLHFQ scores on the 1st day after enrollment. The second (Day 30 after enrollment) was usually obtained by telephone after discharge. The median MLHFQ score was 60 pretreatment and 38.5 posttreatment in the OB group; the scores for the CO group were 59 and 43, respectively. MLHFQ improved in both groups, with a greater improvement in the OB group (P < 0.001). MLHFQ: Minnesota Living With Heart Failure Questionnaire. CO: control group; OB: observation group. n (OB group pretreatment; CO group pretreatment) = 48, n (OB group posttreatment) = 45, n (CO group posttreatment) = 46.

Figure 5. NYHA functional classification results

This figure showed the changes of cardiac function in the two groups after 7 d of treatment. The treatment measures of the two groups were as mentioned above. Before treatment, there were 0, 5 and 43 patients in the OB group with grade II, III and IV heart function, respectively. The numbers of patients with corresponding heart function after treatment were 11, 32 and 5. The corresponding numbers in the CO group were 0, 4, 44, 6, 29 and 13. NYHA: New York Heart Association. CO: control group (n = 48); OB: observation group (n = 48).