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Low Molecular Weight Heparin vs. Regular Heparin or Aspirin
in the Treatment of Unstable Angina Pectoris
Fu
Guosheng, Zhang Xuehua, Shan Jiang
Department of internal cardiology, 2nd affiliated hospital
of Zhejiang Medical University, Hangzhou, China 310003
Abstract:
(1) Aim: Comparing
the curative effect and safety of aspirin alone or combined
with regular heparin of Jipailin (low molecular weight heparin
sodium injection) in treatment of unstable angina pectoris.
Method: 156 unstable angina patients, randomized into: 1)
aspirin (ASP) group; 2) aspirin + regular heparin (ASP + H)
group; 3) aspirin + Jipailin (ASP+JPL) group. Treated for
7 days and followed up for 3-6 months.(2).Results: the remission
rate of ASP + JPL group was significantly higher than that
of ASP group (91.8% VS 58.2%, P<0.001) but not( ASP + H)
group (91.8% VS 80.8%, P>0.05). During the period of follow
up, recurrence rate of angina in ASP + JPL group was significantly
lower than ASP group and (ASP +H) group (12.0% VS 40.6%, 40.5%).
In ASP group, acute myocardial infarct occurred in 7 patients
suffered sudden death; bleeding tendency occurred in 2 patients
of (ASP + H) group. APTT and CT in the 3 groups showed no
significant changes (P>0.05) (3).Conclusion: the use of
Aspirin plus Jipailin is more effective and safer than Aspirin
alone and Aspirin plus regular heparin in the treatment of
unstable angina pectoris.
Unstable angina
is a series of syndromes between stable angina pectoris and
acute myocardial infarction. Its etiology relates with platelet
aggregation, thrombosis and plaque rupture. The present study
investigated the efficacy of Aspirin alone or with regular
heparin or Low Molecular Weight Heparin (LMWH), plus routine
treatment, in treatment of 156 unstable angina pectoris patients.
1 Material and methods
1.1 Patients and
drugs
156 unstable angina pectoris patients, 110 males and 46 females,
averaged age 61.8 (38-78). Diagnosis in accordance with the
nomination and diagnosis standard suggested by 1st National
Academic Symposium of Internal Medicine held in 1980 and WHO[1].
Angina types: 46 of novel fatigue angina, 59 of worsen fatigue
angina, 31 of spontaneous angina (including 5 of variant angina
pectoris) and 23 of post-infarct angina pectoris. 20 patients
underwent coronary angiography, among which 12 were uni-branched
lesion, 5 were bi-branched lesion and 3 were tri-branched
lesion.
Low Molecular Weight Heparin Sodium injection (LMWH, commercial
name: Jipailin (JPL)) was provided by Hangzhou Jiuyuan Gene
Engineering Co., Ltd, specification: 5000IU/2ml.
1.2 The period
and method of treatment
All patients were routinely treated by nitroglycerin and Ca2+
antagonist when hospitalized and plusβ-receptor blocker when
necessary. They were randomized into: 1) Aspirin (ASP) group:
55 patients, each received Aspirin 100 mg/d; 2) Aspirin plus
regular heparin (ASP+H) group: 52 patients, each received
Aspirin 100 mg/d, plus regular heparin 120 IU/kg/d, added
in N.S, 1500 IU/h micropump injected twice daily for 7 days;
3) Aspirin plus Jipailin (ASP+JPL) group: 49 patients, besides
Aspirin, each received Jipailin 120 IU/kg/d, added in N.S,
1500 IU/h micropump injected twice daily for 7 days. Routine
treatments were continued for all patients, by 3-6 month of
follow-up.
1.3 Observation
indexes
Comparing the following indexes in 3 groups: 1) recovery rate
of angina pectoris; 2) recurrence rate of angina pectoris;
3) incidence of myocardial infarction and sudden death(SD);
4) ST-T changes of EKG and dynamic EKG; 5) changes of blood
coagulating state; 6) side effects.
1.4 Evaluation
of curative effect
Excellent: no subsequent
angina pectoris, physical action tolerance increased, drop
of ST segment and turn over of T wave of EKG recovered to
normal or ST-T changes obviously improved, consumption of
nitroglycerin reduced for 50-80%;
Effective: attacks of angina pectoris decreased for 50-80%,
24 hour Holter monitoring showed incidence of myocardial ischemia
reduced over 50% or drop of ST segment decreased for 0.1mv,
consumption of nitroglycerin reduced 30-50%;
Invalid: the incidence of angina pectoris and consumption
of nitroglycerin decreased less than 30%.
1.5 Statistics
All data were expressed
with Mean±SD and were analyzed by t-test and c2 test.
2 Results
2.1 Comparison
of curative effect and side effect (see table 1)
Table 1 Comparison of curative effects and side effects of
the 3 groups
Group
|
Case number |
Excellent
rate(%) |
Effective
rate(%) |
Recurrence
rate(%) |
AMI(case)
|
SD(case)
|
Bleeding(case)
|
| ASP |
55
|
58.2 |
29.1 |
40.6 |
7
|
6
|
0
|
| ASP+H |
52 |
80.8** |
19.2 |
40.5 |
0
|
0
|
2
|
| ASP+JPL |
49 |
91.8## |
8.2 |
12.0*# |
0
|
0
|
0
|
Notes: excellent
rate refered to recovery rate of angina pectoris, ** P<0.01
## P<0.001 compared with ASP group; *P<0.05 compared
with ASP group; # P<0.05compared with ASP+H group.
Recovery rates of angina pectoris were significantly increased
in ASP+H group and ASP+JPL group, and recurrence rate decreased
in ASP+JPL group.
2.2 Changes of
EKG and dynamic EKG
The percentages
of EKG recovered to normal or ST-T changes improved significantly
in the 3 groups were: ASP group 63.6%, ASP+H group 90.4%,
ASP+JPL group 95.9%. Percentage of 24 hour monitoring showing
incidence of myocardial ischemia reduced over 50% or drop
of ST segment reduced over 0.1mv in the 3 groups were: ASP
group 67.3%, ASP+H group 94.2%, ASP+JPL group 98.0%.
2.3 Changes of
blood coagulating state
APTT, CT (tube
method) and changes of platelet aggregation is tabulated in
table2.
Table 2 Comparison
of APTT, CT and platelet aggregation (PA) in 3 groups.
|
|
Before treatment
|
|
After treatment
|
|
ASP group
|
ASP+H group
|
ASP+JPL group
|
ASP group
|
ASP+H group
|
ASP+JPL group
|
|
APTT(s)
|
12.2±0.7
|
11.8±0.7
|
11.6±0.6
|
12.5±0.9
|
12.3±0.8
|
12.4±0.7
|
|
CT(s)
|
7.4±3.8
|
7.6±3.5
|
7.8±3.7
|
8.2±3.9
|
8.5±3.4
|
8.4±3.6
|
|
PA(%)
|
70.4±4.9
|
71.2±5.6
|
70.9±5.1
|
50.8±3.7*
|
50.2±4.1*
|
49.8±4.2*
|
Note: * P<0.001
compared with corresponding items before treatment
3 Discussion
Present study showed
regular heparin and Jipailin exhibit a high effective rate
in the
treatment of unstable angina pectoris, and decreased cardiac
affairs of the patients as well. LMWH could reduce recurrence
rate of angina pectoris, was safer and caused less hemorrhagic
complications, the results were similar with other reports
[2].
The etiological mechanism of unstable angina relates with
platelet aggregation, thrombosis and instability of plaques,
the process is usually mediated by thrombin and depending
on the action of platelet, and does not react completely to
the traditional aspirin and heparin treatment [3]. However,
clinical pharmacological researches demonstrated that unstable
angina pectoris reacts well to anti-thrombosis treatment [4].
Present study suggested that anti-platelet treatment by aspirin
did not give any satisfactory curative efficacy in treatment
of unstable angina, with still high near stage recurrence
rate of angina pectoris and incidence of cardiac affairs.
With additional use of regular heparin or LMWH, the effective
rate was improved significantly, meanwhile cardiac affairs
decreased.
LMWH is fragments
of regular heparin, Jipailin was obtained by cleaving regular
heparin into small segments with its averaged molecular weight
about 4000 dalton. It exhibits strong anti-Xa activity and
much weaker anti-IIa activity, with its anti-Xa/anti-IIa ratio
3-4:1. Administration of prophylactic or treatment dose of
LMWH has rapid and sustained anti-thrombosis effect, with
slight influence on blood coagulation and platelet function,
and need no monitoring of hemocoagulating status [5]. Therefore
LMWH has stronger anti-thrombosis effect and less risk of
hemorrhagic complications. Present study found JPL group has
lower recurrence rate of angina and with no hemorrhagic complication,
could be taken as manifestations of its basic pharmacological
characteristics.
Reference
1. Cardiovascular
disease group of 1st National Academic Symposium of Internal
Medicine. Suggestions for nomination and diagnosis standard
of coronary heart diseases. Chinese Journal of Cardiovascular
Disease 1981, 9(1): 75
2. Gurfinkel EP, Manos EJ, Mejail RL, et al. Low molecular
weight heparin versus regular heparin or aspirin in the treatment
of unstable angina and sident ischemia. J Am Coll Cardial
1995, 26(2):313
3. Harker LA, Maraganore JM, Hirsh J. Novel anti-trhombotic
agents. In Colman RW, Hirsh J, Marder VJ, editors. Hemostasis
and thrombosis: Basic principles and clinical practice. Philadelphia:
JB Lippincott, 1994, 1638-60
4. The RISC group. Risk of myocardial infarction and death
during treatment with low dose aspirin and intravenous heparin
in men with unstable coronary disease. Lancet 1990, 336:827
5. Hirsh J. Low molecular weight heparin. Thromb Haemost 1993,
70: 204
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