A clinical study of JIPAILIN on treating unstable angina pectoris

HE Yong, LIAO Yuhua, WANG Zhaohui, FANG Yuzhen, WANG Qiufen, PANG Hong
Dept. of Cardiology, Union Hospital, Central China University of Science and Technology (430022)

ABSTRACT [Objective] To study the efficacy and safety of JIPAILIN (Low Molecular Weight Heparin sodium Injection) on treating unstable angina pectoris (UAP) [Methods] Fifty-nine patients of UAP were randomized into control group (traditional therapy group) and JIPAILIN group. Daily angina attack times, nitroglycerin consumption, ΣST, PLT, APTT, PT, CK & CK-MB, TNI, myocardiac infarction, sudden death and bleeding complications were observed and compared before and after treatment. [Results] Comparing to control group, there were less angina attack times, less consumption of nitroglycerin as well as abatement of myocardial ischemia (by regular ECG) observed in JIPAILIN group. No myocardiac infarction or sudden death reported during hospitalization. There was no significant difference in PLT, CK & CK-MB, TNI between the two groups whereas slight prolongation of APTT and PT were observed. [Conclusion] The combination of JIPAILIN and Aspirin has better efficacy, safety and less side effects than Aspirin alone in the treatment of UAP.

Clinically, UAP is an acute coronary syndrome commonly encountered. The pathologic and physiologic bases of UAP include disruption of atherosis plaques, attachment and aggregation of platelets and thrombosis etc. UAP can easily develop into myocardiac infraction if without timely and effective treatment. Anticoagulation therapy is effective. The results of JIPAILIN in treating 30 cases of UAP patients are reported in this paper.

Materials and methods

Patients enrollment: Totally 59 cases of hospitalized UAP patients were enrolled, of which incipienty 20 cases, exacerbation tiredness 18 cases, mixed angina 16 cases, post-myocardiac infarction angina 5 cases; male 40 cases, female 19 cases; age between 57~82 years. All patients were judged as UAP according to the diagnosis standards set up by WHO in 1979, without contraindication to anticoagulants. Patients were randomized into JIPAILIN group (30 cases) and control group (29 cases). Age, sex and general conditions were similar between the two groups so as to afford comparability.

Methods: All enrolled patients received Aspirin 100mg (enteric soluble) once daily as well as standard anti-angina therapies. In JIPAILIN group, JIPAILIN (manufactured by Hangzhou Jiuyuan Gene Engineering Co., Ltd.) 0.5ml (5000 IU) was injected s.c. abdomen once per 12 hours, for consecutively 7 days.

Observation indexes: Angina attack times (/day) and nitroglycerin consumption, ΣST, PLT, APTT, PT, CK & CK-MB, TNI, occurrence of myocardiac infarction and sudden death, bleeding complications were observed before and after treatments.

Statistical methods: All data were expressed with Mean±SD and t tests were applied between groups.

Results

1. Curative effects: The angina and myocardiac ischemia conditions before and after treatment in control and JIPAILIN group were shown in Table 1.

Table 1. Clinical symptoms comparison between two groups pre and after treatments

	Control group		JIPAILIN group
	Pre treatment	After treatment	Pre treatment	After treatment
Angina attack times (/day)	2.3±0.9	0.7±0.2	2.4±0.9	0.5±0.1 *,**
Consumption of nitroglyerin	1.3±0.3	0.3±0.05	1.3±0.3	0.1±0.02 *,**
Regular ECG ΣST down shift (mm)	2.6±0.7	1.5±0.51	2.7±0.7	1.3±0.44 **

*: Comparing to control group, P<0.01; **: comparing to pre-treatment, P<0.01

2. Laboratory indexes: PLT, CK, CK-MB, TNI were of no significant difference before and after treatment in both groups, whereas PT and APTT were slightly extended (P<0.05).

Table 2. Laboratory indexes comparison between two groups pre and after treatments

	Control group		JIPAILIN group
	Pre-treatment	After treatment	Pre-treatment	After treatment
PLT (x109/L)	171.4±46.7	168.5±44.3	166.6±42.4	169.8±41.8
PT (S)	11.82±0.84	11.71±0.82	11.74±0.81	13.38±1.11 *,**
APTT (S)	25.66±3.72	26.31±3.83	24.97±4.01	29.81±6.03 *,**
INR	0.94±0.15	0.98±0.17	0.93±0.15	1.06±0.18
CK (u/L)	78.5±12.2	72.6±1.18	79.2±12.3	73.5±10.1
CK-MB (U/L)	26.3±8.31	24.85±8.81	25.44±7.9	23.82±8.13
TNI (ng/L)	0.24±0.09	0.23±0.08	0.25±0.07	0.20±0.08 **

*: Comparing to control group, P<0.05; **: comparing to pre-treatment, P<0.05

3. Side effects: In JIPAILIN group, one case reported relatively large skin ecchymosis at i.v. site at day 5, which disappeared spontaneously after drug withdrawal without any other complications. In control group, one case reported acute myocardiac infarction at day 4.

Discussion

As the pathologic and physiologic mechanisms of UAP are disruption of atherosis plaques, attachment and aggregation of platelets, releasing of platelet factor, activation of coagulation system and induction of intracavitary formation of incomplete obstructive thrombus, the application of anti-platelet and anti-coagulation agents in treating UAP have their theoretical bases [1]. Current standard anticoagulation therapy in treating UAP is i.v. UFH (unfractionated heparin) plus oral Aspirin, which can reduce and prevent thrombosis so as to improve UAP prognosis.

LMWHs are produced by depolymerization and separation of UFH. Comparing to UFH, LMWHs have higher anti-Xa: anti-II ratio, resulting in less bleeding risk. In addition, LMWHs have lower protein affinity, higher bioavailability and half life time, as well as more predictable anti-thrombosis and anticoagulation function, and more convenient for administration [2, 3].

In ESSENCE [4] study, 3171 patients of UAP and non-Q wave myocardiac infarction were randomized into LMWH group and UFH group to receive said treatment for 2~8 days. The results showed, in LMWH group, mortality, number of MI and recurrent angina rate significantly decreased after 48 hours, as well as on day 14 and day 30. The effect even existed after one year follow-up. In our study, the results of JIPAILIN and Aspirin combination therapy in treating UAP were investigated. Comparing to pre-treatment and control group, angina attack frequency was reduced, myocardiac ischemia was improved, and no significant side effect was observed except one case reported skin ecchymosis at i.v. site which spontaneously disappeared after drug withdrawal, demonstrating the good efficacy and safety of JIPAILIN in treating UAP.

References

Kirkeboen KA. Unstable angina pectoris pathogenesis treatment and prognosis. Tidsskr Nor Lageaforen, 1995 (27); 115k: 3376-3381

Hirsh J, Levine MN. Low molecular heparin. Blood, 1992, 79: 1~17

Faceed J, Hoppensteadt DA. Pharmacology of low molecular weight heparins. Semin Thromb Hemost, 1996, 22(suppl 2): 13~18.

Cohen M, Demers C, Gurfinke EP, et al. A comparison of Low-Molecular-Weight Heparin with Unfractionated Heparin for Unstable Coronary Artery Disease. New England Journal of Medicine. 1997; 337: 447~452.