Clinical Intervention Effect of Compound Danshen Dripping Pills on Aspirin Resistant Patients with Coronary Heart Disease

Rubing BAI, Xiaoli SONG

1. Heart Center, Datong Third People’s Hospital, Datong 037008, China; 2. Datong Second People’s Hospital, Datong 037000, China

Abstract [Objectives] To study the clinical intervention effect of Compound Danshen Dripping Pills on aspirin-resistant patients with coronary heart disease (CHD). [Methods] 240 patients with coronary heart disease who took Aspirin were selected to measure thrombocytopenia by sonoclot. They were randomly divided into four groups: group A (n=60), Compound Danshen Dripping Pills and aspirin. group B (n=60), aspirin; group C (n=60), high dose aspirin; group D (n=60), Compound Danshen Dripping Pills. CR and PF were determined by sonoclot after one month. The incidence of angina pectoris, acute myocardial infarction, sudden cardiac death and hemorrhage were observed. [Results] After treatment, the CR and PF levels of group A and C were significantly lower than those before treatment, and there was no significant difference between group B and D and before treatment. After treatment, the levels of CR and PF in group A and C were significantly lower than those in group B and D, and there was a significant difference. Angina pectoris and myocardial infarction events in group D were significantly higher than the other four groups; hemorrhage events in group C were significantly higher than the other three groups. [Conclusions] Compound Danshen Dripping Pills combined with aspirin can be used as an economical, effective, and more dependent alternative to inhibit platelet activity in aspirin resistance, and can further reduce the occurrence of acute coronary events.

Key words Aspirin, Resistance, Sonoclot, Compound Danshen Dripping Pills

1 Introduction

Aspirin resistance (AR) refers to a phenomenon of aspirin failing to effectively inhibit platelet aggregation and thromboxane formation after standardized use of aspirin, and failing to effectively prevent thromboembolic events[1-2]. The occurrence of AR mainly exists in the application of secondary prevention of ischemic cardiovascular and cerebrovascular diseases. If it is not detected and treated in time, it is likely to lead to adverse consequences. In this study, we intended to explore the clinical intervention effect of Compound Danshen Dripping Pills on aspirin-resistant patients with coronary heart disease (CHD).

2 Materials and methods

2.1 Objects and groupingWe selected 240 cases of outpatient and inpatients from October, 2016 to January, 2018 in the diagnosis of stable coronary heart disease with stable angina pectoris in Datong Third People’s Hospital, regularly taking aspirin 100 mg once a day, with an average taking time of (1.52±0.42) years, diagnosed by Sonoclot coagulation and platelet function analyzer as patients with aspirin resistance. Those who have any one of the following conditions were excluded: (i) combined infection; (ii) combined with rheumatic immune system disease; (iii) combined with malignant tumors, severe heart failure (NYHA IV); (iv) severe liver and kidney failure.

2.2 Treatment methodsThe patients (240 cases) were randomly divided into four groups. Group A (n=60) was given Compound Danshen Dripping Pills (10 capsules each time, 3 times/d) combined with aspirin (100 mg/time, 1 time/d); group B (n=60) was given aspirin (100 mg/time, 1 time/d), group C (n=60) was given aspirin (150 mg/time, 1 time/d), group D (n=60) was given Compound Danshen Dripping Pills (10 capsules each time, 3 times/d) treatment. During the treatment period, all patients continued to take nitrate drugs, β-blockers, and lipid-lowering drugs.

2.3 Observation indicatorsAt the time before grouping and one month after treatment, Sonoclot coagulation and platelet function analyzer was used to measure the clotting rate (CR) and platelet function (PF) values of the four groups. Outpatient or inpatient follow-up records were made for all patients’ clinical endpoint events during the treatment period: including the incidence of unstable angina pectoris, acute myocardial infarction, sudden cardiac death, and hemorrhage clinical endpoint events. No loss of follow-up.

3 Results

3.1 Comparison of baseline data of the four groups of patientsThere was no significant difference between four groups of patients in gender, age, body mass index, smoking, family history of coronary heart disease, combined with hypertension, diabetes,etc. (P>0.05) (Table 1).

Table 1 Comparison of baseline data of the four groups of patients n=60)

3.2 Comparison of CR and PF levels of the four groups of patients before and after treatmentThe CR and PF levels in group A and C after treatment were significantly lower than before treatment (P<0.05), which means that platelet function was significantly inhibited; there was no significant difference between the CR and PF levels of group B and D compared with that before treatment (P>0.05), indicating that platelet function has not been inhibited (Table 2 and Table 3).

Table 2 Comparison of CR values before and after treatment in each group n=60)

Table 3 Comparison of PF values before and after treatment in each group n=60)

3.3 Comparison of CR and PF levels between the four groups of patients after treatmentThere was no significant difference in CR and PF levels between group A and group C (P>0.05); there was no significant difference in CR and PF levels between group B and group D (P>0.05); the levels of CR and PF in group A and group C were significantly lower than those in group B and group D, which was statistically significant (P<0.05) (Table 4).

Table 4 Comparison of CR and PF values between groups after treatment n=60)

3.4 Comparison of clinical endpoint events between the four groups of patientsThe hemorrhage event in group C was significantly higher than the other three groups, and the difference was significant (P<0.05); the angina pectoris and myocardial infarction events in group D were significantly higher than the other three groups, and the difference was significant (P<0.05); there was no significant difference in sudden cardiac death between the four groups (P>0.05) (Table 5).

Table 5 Comparison of clinical endpoint events between the four groups of patients [case (%), n=60]

4 Discussion

For over 100 years since its invention, aspirin has been proved by multi-center clinical trials that it has a significant effect in the treatment of coronary heart disease and is the cornerstone of antiplatelet therapy. InClinical Use of Aspirin in Patients with Atherosclerotic Cardiovascular Disease:2005 Chinese Expert Consensus Document, it is pointed out that all patients with coronary heart disease whose application of aspirin to antiplatelet therapy is significantly greater than the risk of hemorrhage. The recommended dose of aspirin is 100 mg/d (75-150 mg/d) for long-term oral use. However, in clinical work, despite the standardized use of aspirin for antiplatelet aggregation therapy, some patients still have no obvious curative effect, and thromboembolic events may even occur. The existence of this individual difference indicates that these patients may have aspirin resistance (AR)[3-4], there are reports that the incidence is about 5% to 45%. The Compound Danshen Dripping Pills is traditional fixed compound preparation made from traditional Chinese medicines such as Salviae Miltiorrhizae Radix Et Rhizoma, Notoginseng Radix Et Rhizoma and Borneolum Syntheticum, and the main component is Benzeneacetic acid-based water-soluble phenolic acids[5]. From the perspective of traditional Chinese medicine, Salviae Miltiorrhizae Radix Et Rhizoma has the effects of dispelling blood stasis, dredging collaterals, relieving pain, promoting blood circulation and removing blood stasis, and emptying worries and relieving restlessness. It can expand coronary blood vessels, increase blood flow, improve myocardial hypoxia, resist oxidation, and scavenge oxygen free radicals, thereby resisting myocardial ischemia and improving coronary microcirculation. Salviae Miltiorrhizae Radix Et Rhizoma is often used clinically to relieve angina pectoris[6]. Sonoclot coagulation and platelet function analyzer is an instrument for measuring coagulation and platelet functioninvitro[7]. Its working principle is as follows: insert a probe connected to an ultrasonic sensor into 0.4 mL of a non-anticoagulated whole blood sample collected from a patient’s vein. The probe vibrates up and down at a frequency of 200 Hz to convert the resistance into an electrical signal. The viscosity changes during the whole coagulation process of the blood specimen are the values obtained by measuring the entire coagulation and platelet function. There are few studies on the application of Sonoclot coagulation and platelet function analyzer to measure platelet activity to guide coronary heart disease anticoagulation and antiplatelet aggregation. There is still no standard guideline alternative for aspirin resistance.

In this experiment, the four groups of treatment programs, after one month of treatment, the CR and PF values were measured by Sonoclot. The levels of CR and PF in group A and group C were significantly lower than those before the experiment and there was no significant difference between the two groups. There was no significant difference between group B and group D compared with before the experiment. These show that the Compound Danshen Dripping Pills in group A combined with aspirin or the increased dose of aspirin in group C can effectively inhibit the platelet activity of aspirin-resistant patients with coronary heart disease, and further reduce the occurrence of acute coronary events, and the efficacy of the two programs is similar, and both can significantly improve aspirin resistance. By comparing the clinical end point events of the four groups of patients, it was found that the angina pectoris and myocardial infarction events in group D were significantly higher than those in the other three groups, indicating that the single use of Compound Danshen Dripping Pills has a poorer effect on coronary heart disease. Hemorrhage events in group C were significantly higher than those in the other three groups, indicating that increased aspirin doses would increase the risk of hemorrhage. It is true that clopidogrel can also be used for aspirin resistance, but it is expensive. In summary, there are two effective alternatives for aspirin resistance: one is to increase the conventional dose of aspirin, and hemorrhage events increase, and proton pump inhibitors may need to be added to prevent hemorrhage. The other is combined use of aspirin and Compound Danshen Dripping Pills. Compound Danshen Dripping Pills combined with aspirin, as an economical, effective, and more dependent alternative to inhibit platelet in aspirin resistance, can activity further reduce the occurrence of acute coronary events.