Clinical
observation of JIPAILIN in treating unstable angina pectoris
ZHANG
Hailei and ZHANG Dawei
Dept.
of Cardiology, People’s Hospital in Putuo, Shanghai
ABSTRACT [Objective] To study the efficacy
and safety of JIPAILIN (a Low Molecular Weight Heparin
sodium Injection) combined with Aspirin in the treatment
of unstable angina pectoris (UAP) [Methods] Forty-five
patients of UAP were randomized into 2 groups. In control
group, traditional therapy and Aspirin were applied whereas
in LMWH group, JIPAILIN was added. Clinical manifestation
of angina attack and other coagulation biochemical indexes
were observed. [Results] Comparing to control group, angina
symptoms were significantly improved (P<0.05) in JIPAILIN
group whereas coagulation biochemical indexes were not
significantly different (P>0.05). Therefore, the combination
of JIPAILIN and Aspirin is safe and effective in treating
UAP, with convenient administration.
Key
words: unstable angina pectoris, Low Molecular Weight
Heparin, Aspirin
The main pathologic and physiologic processes of
UAP include disruption of atherosclerosis plaques, attachment
and aggregation of platelets, releasing of platelet factor,
mural thrombosis induced by activation of coagulation
system, resulting in incomplete vascular occlusion [1].
In recent years, anticoagulation therapy (Aspirin combined
with UFH) in early phase has been recommended in order
to prevent formation and enlargement of thrombus. However,
the application of UFH (unfractionated heparin) is clinically
limited due to its low bioavailability, difficult dose
adjustment, necessity of APTT monitoring, spontaneous
bleeding and high rate of thrombocytopenia. Therefore,
LMWH has been taking the place of UFH. Hereby we report
the efficacy of JIPAILIN in treating UAP in our department.
Objects
and Methods
Objects:
Forty-five patients of UAP hospitalized during October
1999 and November 2000 were enrolled, of which male 24
cases: female 20 cases, age between 45~76 years, by average
55 years. All cases meet the nomination and diagnosis
standards of ischemic heart disease 1979 [2], with no
recent administration of anticoagulant or contraindication
to anticoagulant.
Methods:
Patients were randomized into two groups. Control group:
male 13 cases, female 9 cases; average age 54.3±6 years; regular anti-angina
therapy was administrated including nitroglycerin intravenous
drip, beta-receptor blocker, calcium antagonist and oral
enteric soluble Aspirin 50mg/day. JIPAILIN group: male
13 cases, female 10 cases; average age 53.5±5
years; in addition to regular therapy, JIPAILIN (a LMWH
produced by Hangzhou Jiuyuan Gene Engineering Co., Ltd.)
5000 IU was administered s.c. abdomen twice a day for
consecutively 7 days.
Observation
indexes: Angina attack times and lasting time, change
of ECG and ST-T, platelet counting, prothrombin time,
APTT (Activated partial thrombin time), thrombin time
and fibrinogen were recorded pre and post drug administration.
Statistical
methods: t and x2 tests were applied and P<0.05
was deemed as statistically significant.
Results
No
acute myocardiac infarction occurred in either group.
The clinical improvements of both groups were shown in
table 1:
Table
1. Clinical and ECG changes of UAP patients in both groups
| |
JIPAILIN
group (n=23)
|
Control
group (n=22)
|
|
Pre
treatment
|
Post
treatment
|
Pre
treatment
|
Post
treatment
|
|
Angina
attack times( /day)
|
3.8±2.2
|
1.1±0.5
|
3.8±2.3
|
2.2±1.4
|
|
Nitroglycerin
consumption
|
6.1±2.5
|
3.4±1.5
|
6.2±1.9
|
4.6±1.6
|
|
ST
down shift 0.05~0.1 mV
|
13
|
5
|
12
|
7
|
|
ST
down shift >0.1 mV
|
9
|
2
|
10
|
8
|
|
T
wave reverse
|
15
|
5
|
16
|
11
|
(Comparing
between the two groups, except ST down shift 0.05~0.1
mV, all other indexes showed significant difference with
P<0.05.)
The
laboratory indexes of both groups pre and post treatment
were shown in table 2.
Table
2. Laboratory indexes of UAP patients pre and post treatment
in both groups
| |
JIPAILIN
group (n=23)
|
Control
group (n=22)
|
|
Pre
treatment
|
Post
treatment
|
Pre
treatment
|
Post
treatment
|
|
Platelet
count (x 109/L)
|
177±37.2
|
171±33.3
|
176±34.2
|
173±35.9
|
|
prothrombin
time (s)
|
13.5±1.8
|
14.6±1.6
|
13.4±1.7
|
14.1±1.5
|
|
APTT
(s)
|
37.3±4.3
|
41.2±5.4
|
38.8±4.3
|
40.4±4.5
|
|
Thrombin
time (s)
|
16.4±1.8
|
17.1±1.6
|
15.8±1.2
|
16.3±1.4
|
|
Fibrinogen
(g/L)
|
3.6±1.2
|
3.2±1.4
|
3.5±1.3
|
3.3±0.8
|
(Comparing
between the two groups, all 5 indexes showed no significant
difference pre and post treatment, with P>0.05.)
Side
effects: Three cases and two cases of occult blood in
stool reported in JIPAILIN and control group, respectively.
Both were improved after receiving H2 receptor
blocking agent treatment. One case of gingival bleeding
and seven cases of skin ecchymosis at i.v. abdomen site
reported in JIPAILIN group whereas skin ecchymoses were
gradually absorbed after changing injection site. No severe
thrombocytopenia or organ bleeding was observed.
Discussion
LMWHs
are produced by chemical or enzymic depolymerization of
UFH, with average molecular weight of about 4000~6000
Daltons. LMWHs are featured by their complete absorption
after s.c. injection, long half life time (about 2 times
as that of UFH), high bioavailability (87%~98%), and the
same penta-saccharide fragment as UFH which can be recognized
by anti-thrombin. The binding of LMWH with anti-thrombin
enhanced the affinity between anti-thrombin and anti-Xa
so as to reduce its activity, resulting in inhibition
of thrombin cascade. Due to the lower content of long
molecule which is necessary to inhibit anti-IIa, LMWH
has a lower anti-IIa activity than UFH. Suppose the anti-Xa:
anti-IIa ratio of UFH is 1: 1, the ratio of LMWH is about
2~5 [3]. This is the reason why LMWH has anticoagulation
efficacy without necessity of APTT monitoring clinically.
The possible factors of low thrombocytopenia rate and
low bleeding risk after LMWH administration are: low affinity
to endothelial cells and platelets; less effect in inducing
heparin-dependent IgG genesis; low immune sensitivity;
reduction of platelet activation, PF4 releasing
and its binding to LMWH [4]. In our study, angina symptoms
were improved in both group, nevertheless the addition
of JIPAILIN treatment had better curative effects (statistically
significant, P>0.05), without significant (P>0.05)
effect on BPC, PT, APTT, Fbg etc. JIPAILIN is convenient
to administer, with 1~2 times subcutaneous injection daily
and without necessity of laboratory monitoring. The combination
of JIPAILIN and Aspirin therapy was safe, of low bleeding
risk and could delay coronary thrombosis of UAP patients.
FRISC study [5] showed that the administration of LMWH
to patients of UAP or non-Q wave myocardiac infarction
could significantly reduce mortality and MI rate in the
initial 6 days. In conclusion, the administration of JIPAILIN
in acute phase of UAP for a short period of time is safe,
effective and should be widely practiced.
References
ZHANG
Ningzi and Du Riying: Cardiovascular Disease-theory and
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Nomination
and Diagnosis Standards of Ischemic Heart Disease. Journal
of Chinese Internal Medicine, 1981, 20(4): 254~255.
SUN
Shen et al: Encyclopedia of Clinical Drug Application.
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1994: 275.
FANG
Rongjuan and HE Yiping et al. The clinical application
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1999, 19(9): 564.
FRISC
study group. Low molecular weight heparin during instability
in coronary artery disease. Lancet 1996; 347: 561-8.
