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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 6, November/December 2018
360
AFRICA
clopidogrel group was significantly decreased (both
p
<
0.05).
There was also no significant difference in the risk of thrombosis
between the other two groups. Overall, there was no significant
difference in the total risk of bleeding and thrombosis between
the four groups (
p
>
0.05).
The multivariate logistic regression analysis of MA-ADP
indicated that in the subjects with MA-ADP
<
31 mm, an
increased white blood cell count (OR
=
1.262,
p
<
0.001) was a
risk factor for bleeding, while an increased platelet count (OR
=
0.995,
p
=
0.013) was a protective factor for bleeding. In the
subjects with MA-ADP
>
47 mm, an increased platelet count
(OR
=
1.006,
p
<
0.001), eGFR (OR
=
1.016,
p
=
0.013) and HbA
1c
level (OR
=
1.358,
p
=
0.011) were risk factors for thrombosis.
The other factors, such as the age, APTT and LDL-C were not
risk factors for bleeding or for thrombosis (Table 5).
Discussion
According to the Chinese guidelines,
1
antiplatelet therapy is
essential for patients with coronary artery disease, cerebrovascular
disease or diabetes. This study showed that these retired male
Chinese officers had a high prevalence of cardiovascular and
cerebrovascular diseases, diabetes mellitus and dyslipidaemia.
The use of antiplatelet drug treatments in this population was
approximately 50%.
Currently, aspirin and clopidogrel are the most common
antiplatelet drugs used in clinical practice. The options of
antiplatelet drugs vary depending on different clinical conditions.
In this study, using TEG, we evaluated the efficacy of different
antiplatelet therapies in retired elderly male Chinese officers and
explored the risk factors influencing the efficacy of different
antiplatelet therapies.
The data showed that the inhibition of platelet aggregation
by AA was 48.0
±
19.3% in the aspirin group, and the inhibition
by ADP was 63.0
±
18.2% in the clopidogrel group. The effective
percentage of platelet inhibition in the aspirin and clopidogrel
groups was 45.9 and 76.5%, respectively, which suggests that
clopidogrel might be a more effective antiplatelet therapy than
aspirin. We speculated that this effect might be associated
with the older age of patients in the clopidogrel group. Elderly
patients have a slower metabolic rate (eGFR: 71.69
±
14.48 ml/
min/1.73 m
2
in the aspirin group, and 76.87
±
20.37 ml/min/1.73
m
2
in the clopidogrel group,
p
=
0.0015), which would lead to
an accumulation of antiplatelet drug and therefore enhance the
antiplatelet effect.
Both aspirin and clopidogrel treatments have a risk of bleeding,
and poor antiplatelet effects increase the risk of thrombosis. The
TEG variable MA-ADP is one of the predictors of adverse
cardiovascular events, and the best range of MA-ADP in the
Chinese population is between 31 and 47 mm, according to the
study by Tang
et al
.
8
In our study, patients treated with either
aspirin or clopidogrel monotherapy or a combination of the two
drugs showed average MA-ADP values that were all in the best
range, suggesting that the lowest risk of bleeding and thrombosis
can be achieve with aspirin or clopidogrel alone or in combination.
Compared with aspirin, clopidogrel reduced the risk of
thrombosis and increased the risk of bleeding, which could
be associated with the inhibition of neovascularisation by the
mechanism of action of clopidogrel.
11
The risk of bleeding
and thrombosis in the dual-drug antiplatelet group was not
significantly different from the other three groups. This may
have been related to the small number of subjects in this group.
Overall, there was a low risk of bleeding and thrombosis and
a high safety level for antiplatelet therapy with aspirin and
clopidogrel in combination.
The logistic regression analysis showed that the increased
leukocyte count was a risk factor for bleeding. This is consistent
with the results of other studies. A study showed that leukocyte
overload could result in significant bleeding in patients with
primary thrombocytosis and that a leukocyte count over 1.1
× 10
7
cells/
µ
l was an independent risk factor for acute vascular
events.
12
Another study showed that leukocytes may infiltrate
the endothelial barrier through the G
α
i2 signalling pathway, be
recruited to the inflammatory site, and then cause inflammatory
bleeding.
13
Thirty years ago, the relationship between platelets and TEG
was studied,
14
and it was recently revalidated with the modified
version of TEG. A study from Holland
15
showed that platelets
were significantly and positively associated with MA. When
the platelet count was
<
100 × 10
9
cells/l, the clot formation rate
decreased, and when the platelet count was
<
50 × 10
9
cells/l, the
MA decreased significantly. However, in our study, the platelet
count varied according to the patient’s condition. It was a
protective factor for patients who were prone to bleeding, while it
was a risk factor for the patients who were prone to thrombosis.
The research on TEG in other related diseases is limited.
There are a variety of reasons for renal failure to cause bleeding,
and the most important one may be due to accumulated toxins
that affect the function of platelets, and the interaction between
platelets and the vascular wall.
16
Our study found a slightly
positive association between eGFR and thrombosis in the
patient population with MA-ADP
>
47 mm, but the specific
pathogenesis is not clear and further research is needed.
A study by Yao and co-workers
17
showed that in patients
Table 4. Safety of antiplatelet therapies through different pathways
Risk
Aspirin
group
(
n
=
368)
Clopidogrel
group
(
n
=
115)
Dual-drug
group
(
n
=
43)
No-drug
group
(
n
=
429)
Bleeding risk,
n
, (%)
*
92 (25.0)
41 (35.7)
#
14 (32.6)
94 (21.9)
Safe range,
n
, (%)
†
143 (38.9)
54 (47.0)
17 (39.5) 179 (41.7)
Thrombosis risk,
n
, (%)
‡
133 (36.1)
20 (17.4)* 12 (27.9) 156 (36.4)
*
Bleeding risk refers to MA-ADP
<
31 mm;
†
Safe range refers to MA-ADP 31–47 mm;
‡
Thrombosis risk refers to MA-ADP
>
47 mm.
#
Compared with the aspirin group,
p
<
0.05 (
p
=
0.026).
*Compared with the aspirin group,
p
<
0.05 (
p
=
0.000);
Compared with the no-drug group,
p
<
0.05 (
p
=
0.000).
Table 5. Logistic regression analysis of MA-ADP-related factors
Parameters
MA-ADP
<
31 mm
p
-value
MA-ADP
>
47 mm
p
-value
OR 95% CI
OR 95% CI
Age (years)
0.993 0.98–1.01 0.388 1.006 0.99–1.02 0.717
WBC (× 10
9
cells/l) 1.262 1.12–1.43
<
0.001 0.892 0.79–1.01 0.062
PLT (× 10
9
cells/l)
0.995 0.99–1.00 0.013 1.006 1.00–1.01
<
0.001
APTT (s)
0.985 0.94–1.03 0.522 1.040 1.00–1.08 0.064
LDL-C (mmol/l)
1.033 0.83–1.29 0.770 1.074 0.88–1.32 0.490
eGFR
(ml/(min/1.73 m
2
)
1.003 0.99–1.02 0.013 1.016 1.00–1.03 0.013
HbA
1c
(%)
1.057 0.82–1.37 0.673 1.358 1.07–1.72 0.011
WBC: white blood cell count; PLT: platelet count; APTT: activated partial
thromboplastin time; LDL-C: low-density lipoprotein cholesterol; eGFR: esti-
mated glomerular filtration rate; HbA
1c
: glycated haemoglobin A
1c
.