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Journal of Cardiology xxx (2015) xxxxxx

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Journal of Cardiology
journal homepage: www.elsevier.com/locate/jjcc

Original article

Treatment with cilostazol improves clinical outcome after


endovascular therapy in hemodialysis patients with peripheral
artery disease
Hideki Ishii (MD, PhD)a,*, Toru Aoyama (MD, PhD)b, Hiroshi Takahashi (BSc)c,
Yoshitaka Kumada (MD, PhD)d, Daisuke Kamoi (MD)b, Takashi Sakakibara (MD)b,
Norio Umemoto (MD)b, Susumu Suzuki (MD)a, Akihito Tanaka (MD)a,
Yasuhiko Ito (MD, PhD)e, Toyoaki Murohara (MD, PhD)a
a
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
b
Cardiolovasucular Center, Nagoya Kyoritsu Hospital, Nagoya, Japan
c
Division of Medical Statistics, Fujita Health University, Toyoake, Japan
d
Department of Cardiovascular Surgery, Matsunami General Hospital, Kasamatsu, Japan
e
Department of Renal Replacement Therapy, Nagoya University Graduate School of Medicine, Nagoya, Japan

A R T I C L E I N F O A B S T R A C T

Article history: Background: Cilostazol has been reported to prevent atherosclerotic events in the general population.
Received 23 October 2014 However, data have been limited whether there are benecial effects of cilostazol use on long-term
Received in revised form 17 April 2015 clinical outcomes after endovascular therapy in hemodialysis (HD) patients with peripheral artery
Accepted 1 May 2015
disease (PAD).
Available online xxx
Methods and results: This study consisted of 595 HD patients undergoing endovascular therapy for a
clinical diagnosis of PAD. They were divided into two groups: patients receiving 100 mg cilostazol twice
Keywords:
daily in conjunction with standard therapy (n = 249 patients, cilostazol group) and those not
Cilostazol
Hemodialysis
administered cilostazol (n = 346 patients, control group). A propensity score analysis was performed
Peripheral artery disease to adjust for baseline differences between the two groups. The propensity score-adjusted 10-year event-
Stroke free survival rate from major adverse cardiovascular events (MACE) was signicantly higher in the
Prognosis cilostazol group than in the control group [58.6% vs. 43.7%, hazard ratio (HR) 0.57; 95% condence
interval (CI) 0.410.79; p = 0.0010]. Notably, the adjusted stroke-free rate was signicantly higher in the
cilostazol group than in the control group (81.6% vs. 74.7%; HR = 0.48; 95% CI, 0.250.92, p = 0.028). Even
after adjusting for other confounders, treatment with cilostazol was an independent predictor for
prevention of MACE and stroke (p = 0.0028 and p = 0.039, respectively).
Conclusions: Cilostazol administration improves long-term clinical outcomes including prevention of
MACE and stroke after endovascular therapy in HD patients with PAD.
2015 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.

Introduction for systemic atherosclerosis [3,4]. High prevalence of traditional


risk factors is greatly associated with higher rates of atheroscle-
Peripheral artery disease (PAD) is related to other vascular rotic disease in patients with advanced renal disease [57]. In such
diseases, and is therefore sometimes referred to as a representation situations, cardiovascular events including stroke are commonly
of systemic atherosclerosis [1]. Patients with both PAD and seen in patients on HD, with the relative risk of stroke in patients
cardiac or cerebrovascular disease have a poor prognosis [2]. On with end-stage renal disease (ESRD) estimated to be 510 times
the other hand, patients receiving hemodialysis (HD) are at a risk that of the age-matched general population [8].
Cilostazol, a selective inhibitor of phosphodiesterase 3, inhibits
smooth muscle cell proliferation [9,10]. Chronic treatment with
cilostazol prevents incidence of cardiovascular events including
* Corresponding author at: Department of Cardiology, Nagoya University
stroke in patients with atherothrombosis and it also prevents
Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8550,
Japan. Tel.: +81 52 744 2147; fax: +81 52 744 2157. secondary stroke in Japanese patients [11,12]. However, data
E-mail address: hkishii@med.nagoya-u.ac.jp (H. Ishii). regarding whether such effects extend to subjects receiving HD,

http://dx.doi.org/10.1016/j.jjcc.2015.05.003
0914-5087/ 2015 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.

Please cite this article in press as: Ishii H, et al. Treatment with cilostazol improves clinical outcome after endovascular therapy in
hemodialysis patients with peripheral artery disease. J Cardiol (2015), http://dx.doi.org/10.1016/j.jjcc.2015.05.003
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2 H. Ishii et al. / Journal of Cardiology xxx (2015) xxxxxx

who are considered to be high-risk individuals for atherosclerotic symptoms followed by conrmation on computed tomography
events, are limited. Therefore, the aim of the present study was to and/or magnetic resonance imaging. Diagnosis of myocardial
compare long-term clinical outcomes in HD patients who received infarction was based on new ST-segment changes with at least two
and those who did not receive cilostazol for clinically diagnosed contiguous electrocardiographic leads, and a more than two-fold
PAD after revascularization with endovascular therapy (EVT). elevation of creatine kinase level above the maximum peak in the
normal range. To evaluate lower limb peripheral arteries, we
Methods performed follow-up examinations, including Doppler sonogra-
phy, ankle brachial pressure index (ABI) measurement, and/or
Study population clinical observations 3 months after EVT and every 6 months
thereafter. An angiographical evaluation was performed in cases of
We performed successful EVT for PAD in 626 HD patients with an abnormal Doppler waveform >2.4 m/s, worsening clinical
end-stage renal failure between January 1999 and December symptoms, depressed ABI, worsening critical limb ischemia, and/or
2010. Eligible patients were retrospectively stratied by status of the need for limb amputation.
cilostazol treatment: 249 patients receiving 100 mg oral cilostazol Diabetes was dened as a fasting plasma glucose concentration
twice daily for more than one month before EVT (cilostazol group) >126 mg/dl, a randomized plasma glucose concentration
and 377 patients who did not receive cilostazol (control group). In >200 mg/dl, glycated hemoglobin A1c levels 6.5% and/or use
advance, 31 patients did not receive cilostazol therapy before EVT, of anti-hyperglycemic treatment. Hypertension was dened as a
but initiated oral cilostazol during the follow-up period. Pre- systolic blood pressure >160 mmHg, diastolic blood pressure
determined exclusion criteria included an age >80 years and >90 mmHg, and/or use of anti-hypertensive treatment. Dyslipi-
cancer. All patients received successful procedure dened as a nal demia was dened as low-density lipoprotein levels 140 mg/dl,
luminal diameter stenosis <30% without angiographically visual triglyceride levels 150 mg/dl, and/or high-density lipoprotein
arterial dissection. They received oral aspirin for at least 7 days cholesterol levels <40 mg/dl and/or anti-dyslipidemic medication
before EVT. The study was conducted in accordance with the use. In this study, we dened high-ex membrane as b2
guidelines of the ethics committee in our institution, and was microglobulin clearance 30 ml/min.
approved by the hospital ethics committee. Written informed
consent was obtained from each patient. Statistical analysis
The primary endpoint was incidence of major adverse
cardiovascular events (MACE), dened as a composite of all-cause Statistical analyses were performed using the SPSS 21 software
death, new onset or recurrent stroke including cerebral infarction, program (SPSS Inc, Chicago, IL, USA). Continuous variables were
cerebral hemorrhage and subarachnoid hemorrhage, and non-fatal expressed as mean  standard deviation. Between-group differences
myocardial infarction after EVT. The secondary endpoint was were evaluated with the Student t-test for continuous variables and
major adverse limb events (MALE), a composite of target lesion the chi-square test for categorical variables. Between-group differ-
revascularization (TLR), and major amputation as dened in a ences in event-free survival were evaluated using the KaplanMeier
previous paper [13]. Data were obtained from hospital charts and method and compared using a log-rank test. Hazard ratios (HR) and
through telephone interviews with patients conducted by trained 95% condence intervals (CI) were calculated with a Cox proportional
reviewers. Stroke was diagnosed according to clinical signs and/or hazards analysis.

Table 1
Clinical characteristics.

All patients (n = 595) Cilostazol (n = 249) Control (n = 346) p-Value

Male (%) 65.7 61.8 68.5 0.10


Age (years) 67  10 67  10 68  10 0.67
Diabetes (%) 65.9 63.9 67.3 0.37
Hypertension (%) 66.6 66.7 66.5 0.96
Dyslipidemia (%) 27.1 24.5 28.9 0.23
Smoking (%) 25.7 25.3 26.0 0.84
Body mass index (kg/m2) 21.2  3.4 21.3  3.6 21.1  3.2 0.45
Coronary artery disease (%) 69.9 66.0 72.8 0.078
Stroke (%) 19.0 16.1 20.8 0.14
Indication for EVT (%) 0.41
Intermittent claudication 58.8 57.0 60.1
Rest pain 15.8 18.1 14.2
Ulcer/gangrene 25.4 24.9 25.7
Preoperative ABI 0.62  0.28 0.63  0.26 0.61  0.30 0.58
ACE inhibitors (%) 23.4 24.1 23.1 0.88
A-II receptor blockers (%) 48.2 50.6 47.1 0.58
Warfarin (%) 18.0 19.3 17.3 0.67
Ticlopidine (%) 59.3 61.4 58.4 0.29
High-ux membrane (%) 89.1 92.0 87.0 0.15
Number of lesions 876 348 528
Mean number of lesions (n) 1.5  0.7 1.4  0.5 1.5  0.7 0.071
Lesion location (%) 0.54
Iliac artery 29.5 30.7 28.6
Femoropopliteal artery 70.5 69.3 71.4
TASC classication (%) 0.97
Type A + B 75.1 75.0 75.2
Type C + D 24.9 25.0 24.8
Stent use (%) 66.1 69.8 63.6 0.12

ABI, ankle brachial pressure index; ACE, angiotensin-converting enzyme; A-II, angiotensin II; EVT, endovascular therapy; TASC, TransAtlantic Inter-Society Consensus.

Please cite this article in press as: Ishii H, et al. Treatment with cilostazol improves clinical outcome after endovascular therapy in
hemodialysis patients with peripheral artery disease. J Cardiol (2015), http://dx.doi.org/10.1016/j.jjcc.2015.05.003
G Model
JJCC-1087; No. of Pages 6

H. Ishii et al. / Journal of Cardiology xxx (2015) xxxxxx 3

To adjust for differences in baseline characteristics between the Table 2


Clinical events.
two groups, a propensity score analysis was performed using a
multivariate logistic regression model including all the following All patients Cilostazol Control
baseline covariates: male sex, age, diabetes, hypertension, MACE 173 (29.1%) 50 (20.1%) 123 (35.6%)
dyslipidemia, smoking status, body mass index, previous coronary All-cause death 149 (25.0%) 42 (16.9%) 107 (30.9%)
artery disease, previous stroke, critical limb ischemia, TransAtlan- MI 19 (3.2%) 6 (2.4%) 13 (3.8%)
tic Inter-Society Consensus (TASC) type C or D, femoropopliteal Stroke 50 (8.4%) 13 (5.2%) 37 (10.7%)
Infarction 41 (6.9%) 9 (3.6%) 32 (9.2%)
lesion, and stent use. The score was then incorporated into the Cox
Hemorrhage 9 (1.5%) 4 (1.6%) 5 (1.5%)
proportional hazards model as a covariate. Propensity score- MALE 167 (28.1%) 55 (22.1%) 112 (32.4%)
adjusted event-free survival curves were also constructed. Finally, Major amputation 32 (5.4%) 7 (2.8%) 25 (7.2%)
to identify independent predictors of the endpoints, we used Cox TLR 152 (25.5%) 52 (20.9%) 100 (28.9%)
multivariable regression models including all covariates with MACE, major adverse cardiovascular events; MALE, major adverse limb events;
p < 0.05 on the univariate analysis with propensity score. MI, myocardial infarction; TLR, target lesion revascularization.
Differences were considered statistically signicant at p < 0.05.

Results
in the cilostazol group than in the control group (58.3% vs. 43.6%,
Table 1 shows the patients baseline clinical characteristics. p = 0.0010, HR = 0.57; 95% CI, 0.410.80 and 59.5% vs. 53.5%,
There were no signicant differences between the two groups. p = 0.0056, HR = 0.63; 95% CI, 0.460.87, respectively) (Fig. 1A and
Although coronary artery disease was more frequent in the control B). The KaplanMeier analysis also showed that the cilostazol
group, this did not reach statistical signicance. No signicant group had a higher all-cause stroke-free rate than the control
differences in medications other than cilostazol were seen group (82.0% vs. 74.3%, p = 0.017, HR = 0.46; 95% CI, 0.240.88)
between the two groups. When these medications were evaluated (Fig. 1C). Interestingly, however, the incidence of hemorrhagic
in the multivariate analysis, no signicant effects in clinical stroke was comparable between the two groups (1.6% vs. 1.3%).
outcomes were seen (data not shown).
Table 2 shows the incidence of the study endpoints during the Propensity score analysis
follow-up period (median 41 months, interquartile range: 2157
months). In the cilostazol group, both MACE and MALE were less The propensity score-adjusted MACE-free rate was 58.6% in the
frequent than in the control group. In the KaplanMeier analysis, cilostazol group and 43.7% in the control group (HR = 0.57; 95% CI,
10-year MACE and MALE event-free rates were signicantly higher 0.410.79, p = 0.0010) (Fig. 2A).

(A) 1.0 (B) 1.0


Event-free survival for MALE
Event-free survival for MACE

0.8 0.8
Cilostazol
Cilostazol
0.6 58.3% 0.6 59.5%
53.5%
0.4 43.6% 0.4
Control
Control

0.2 0.2
Log-rank P = 0.0010 Log-rank P = 0.0056
0.0 0.0
0 20 40 60 80 100 120 0 20 40 60 80 100 120
Follow-up period (months) Follow-up period (months)
Cilostazol 249 145 70 45 23 15 0 Cilostazol 249 111 46 27 15 12 0
Control 346 211 116 58 24 14 0 Control 346 145 74 37 16 11 0

(C) 1.0
Event-free survival for Stroke

0.9
Cilostazol
82.0%
0.8
74.3%
0.7 Control

0.6 Log-rank P = 0.017

0.5
0 20 40 60 80 100 120
Follow-up period (months)
Cilostazol 249 149 69 46 24 16 0
Control 346 212 118 61 24 13 0

Fig. 1. (A) The event-free rate from major adverse cardiovascular events (MACE) during 10-year follow-up period. (B) The event-free rate from major adverse limb events
(MALE) during 10-year follow-up period. (C) The event-free rate from stroke during 10-year follow-up period.

Please cite this article in press as: Ishii H, et al. Treatment with cilostazol improves clinical outcome after endovascular therapy in
hemodialysis patients with peripheral artery disease. J Cardiol (2015), http://dx.doi.org/10.1016/j.jjcc.2015.05.003
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4 H. Ishii et al. / Journal of Cardiology xxx (2015) xxxxxx

(A) 1.0 (B) 1.0

Event-free survival for MALE


Event-free survival for MACE 0.8 0.8
Cilostazol
Cilostazol
0.6 58.6% 0.6 59.5%
53.5%
43.7% Control
0.4 Control 0.4

0.2 P = 0.0010 0.2 P = 0.0058

0.0 0.0
0 20 40 60 80 100 120 0 20 40 60 80 100 120
Follow-up period (months) Follow-up period (months)
Cilostazol 249 145 70 45 23 15 0 Cilostazol 249 111 46 27 15 12 0
Control 346 211 116 58 24 14 0 Control 346 145 74 37 16 11 0

(C) 1.0
Event-free survival for Stroke

0.9
Cilostazol
81.6%
0.8
74.7%
0.7 Control

0.6 P = 0.028

0.5
0 20 40 60 80 100 120
Follow-up period (months)
Cilostazol 249 149 69 46 24 16 0
Control 346 212 118 61 24 13 0

Fig. 2. (A) The propensity score-adjusted event-free rate from major adverse cardiovascular events (MACE) during 10-year follow-up period. (B) The propensity score-
adjusted event-free rate from major adverse limb events (MALE) during 10-year follow-up period. (C) The propensity score-adjusted event-free rate from stroke during 10-
year follow-up period.

In a Cox multivariable analysis including other signicant benet of anticoagulation therapy with warfarin for primary stroke
confounders along with the propensity score, cilostazol treatment prevention in patients with ESRD is unclear [18]. Although the
(HR 0.58; 95% CI 0.410.83; p = 0.0028), ulcer/gangrene prevalence prevention of cerebrovascular events and mortality is of clinical
(HR 1.54; 95% CI 1.082.20; p = 0.019), and previous stroke (HR concern, optimal medical therapies have not been established. The
1.79; 95% CI 1.182.70; p = 0.0057) independently predicted MACE main nding of the present study was that treatment with
(Table 3). In addition, cilostazol treatment was signicantly cilostazol had a benecial effect in terms of preventing adverse
associated with the prevention of stroke (HR 0.50; 95% CI 0.26 events such as stroke and mortality in HD patients with PAD.
0.96; p = 0.039). Although it has been previously reported that cilostazol treatment
Propensity score-adjusted MALE-free survival was signicantly prevents stroke in non-HD subjects with PAD, it does not improve
higher in the cilostazol group than in the control group (59.5% vs. the mortality rate in non-HD patients with PAD [11,19]. From the
53.5%, p = 0.0058) (Fig. 2B). After adjustment for other confounders point of such a view, our ndings regarding HD patients were of
along with the propensity score, cilostazol treatment (HR 0.64, 95% clinical signicance.
CI 0.460.88; p = 0.0068), male (HR 1.44, 95% CI 1.012.07, The unique effects of cilostazol include both vasodilation and
p = 0.044), the prevalence of ulcer/gangrene (HR 1.73, 95% CI inhibition of neointimal proliferation [10,2022]. We previously
1.232.43; p = 0.0016), and stent use (HR 0.63, 95% CI 0.460.86; reported that, compared to controls, HD patients with PAD who were
p = 0.0034) were independent predictors of MALE (Table 3). The treated with cilostazol had a higher rate of cumulative patency after
adjusted stroke-free rate during the 10-year follow-up period was EVT [23]. In that study, treatment with cilostazol not only improved
81.6% in the cilostazol group and 74.7% in the control group the patency of the lower extremities but also prevented stroke and
(HR = 0.48; 95% CI, 0.250.92, p = 0.028) (Fig. 2C). adverse events. One study has reported that HD patients have
As shown in Table 3, compared to the control group, the abnormal platelet function [24,25]. In addition, HD itself may induce
cilostazol group had a higher event-free rate for MACE, all-cause plasma coagulation factors [26]. These mechanisms may cause
death, stroke, MALE, major amputations and TLR. thrombus formation in HD patients. In that study, ischemic stroke
was signicantly prevented in the cilostazol group. By contrast,
Discussion bleeding risk also increases in HD patients [6]. Interestingly, cerebral
hemorrhage events were not increased in the cilostazol group in our
Patients with ESRD have a risk of cardiovascular events that is study. In other words, administration of cilostazol did not affect
2030 times higher than that of the general population [14]. In intracranial hemorrhage, which is consistent with the ndings of
addition, the mortality rate of stroke is also high in patients with previous studies [27]. From such points, our ndings may have
ESRD [15,16]. Renal dysfunction has been shown to independently clinical signicance for the treatment of HD subjects.
predict poor neurological outcomes, and the frequency of stroke Limitations should be considered when interpreting the data of
has been shown to be higher in patients with ESRD [17]. The the study. First, the study had a single-center design with a limited

Please cite this article in press as: Ishii H, et al. Treatment with cilostazol improves clinical outcome after endovascular therapy in
hemodialysis patients with peripheral artery disease. J Cardiol (2015), http://dx.doi.org/10.1016/j.jjcc.2015.05.003
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H. Ishii et al. / Journal of Cardiology xxx (2015) xxxxxx 5

Table 3
Unadjusted and adjusted hazard ratios of cilostazol for clinical events.

Crude Propensity score-adjusted Risk-adjusted with propensity scorea

HR (95% CI) p-Value HR (95% CI) p-Value HR (95% CI) p-Value

MACE
Cilostazol use 0.57 (0.410.80) 0.0011 0.57 (0.410.79) 0.0010 0.58 (0.410.83) 0.0028
Male 1.41 (0.952.09) 0.086
BMI 0.96 (0.911.02) 0.20
Ulcer/gangrene 1.54 (1.082.20) 0.019
Previous stroke 1.79 (1.182.70) 0.0057
All-cause death
Cilostazol use 0.56 (0.390.80) 0.0015 0.55 (0.380.78) 0.0010 0.59 (0.380.92) 0.020
Male 1.26 (0.811.96) 0.29
BMI 0.93 (0.870.99) 0.030
Ulcer/gangrene 1.60 (1.012.55) 0.048
Stroke
Cilostazol use 0.46 (0.240.88) 0.020 0.48 (0.250.92) 0.028 0.50 (0.260.96) 0.039
Previous stroke 8.05 (4.1715.55) <0.0001
MI
Cilostazol use 0.64 (0.241.68) 0.36 0.63 (0.241.66) 0.36 0.79 (0.302.09) 0.64
Male 3.10 (1.088.84) 0.034
Age 1.04 (0.991.08) 0.098
MALE
Cilostazol use 0.63 (0.460.87) 0.0056 0.63 (0.460.87) 0.0058 0.64 (0.460.88) 0.0068
Male 1.44 (1.012.07) 0.044
Ulcer/gangrene 1.73 (1.232.43) 0.0016
Stent use 0.63 (0.460.86) 0.0034
Major amputation
Cilostazol use 0.41 (0.180.96) 0.040 0.41 (0.170.95) 0.039 0.41 (0.180.96) 0.039
Ulcer/gangrene 4.63 (2.279.43) <0.0001
TLR
Cilostazol use 0.67 (0.480.93) 0.018 0.67 (0.480.94) 0.021 0.68 (0.490.95) 0.023
Stent use 0.65 (0.480.89) 0.0075

BMI, body mass index; CI, condence interval; HR, hazard ratio; MACE, major adverse cardiovascular events; MALE, major adverse limb events; MI, myocardial infarction;
TLR, target lesion revascularization.
a
Adjusting for covariates with p < 0.05 by univariate analysis with propensity score.

number of enrolled patients. Second, this was not a prospective, JMS Co., Ltd., Kyowa Hakko Kirin Co., Ltd, MSD K.K., Takeda
randomized, double-blind, controlled study, although a propensity Pharmaceutical Co., Ltd., and Terumo Co., Ltd. T.M. received lecture
score analysis was conducted. The use of propensity-matched fees from Bayel Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd.,
scores may minimize but does not eliminate selection bias. The Dainippon Sumitomo Pharma Co., Ltd., Kowa Co., Ltd., MSD K.K.,
scores indicate that the decision to use or not use cilostazol was not Mitsubishi Tanabe Pharma Co., Nippon Boehringer Ingelheim Co.,
random. Thus, unseen or unmeasured biases in the interpretation Ltd., Novartis Pharma K.K., Pzer Japan Inc., Sano-Aventis K.K.,
of our results could not be ruled out. Third, the effects of other and Takeda Pharmaceutical Co., Ltd. Y.I. received unrestricted
specic drugs and/or drug combinations may have affected the research grant from Daiichi Sankyo Co., Ltd., Kyowa Hakko Kirin
results. Fourth, recent studies have shown that a good clinical Co., Ltd, and MSD K.K. T.M. received unrestricted research grant for
outcome is achieved in patients with residual renal function even if Department of Cardiology, Nagoya University Graduate School of
they are treated with HD [28,29]. In this study, we did not routinely Medicine from Astellas Pharma Inc, Daiichi Sankyo Co., Ltd.,
evaluate residual renal function. Finally, exercise tolerance was not Dainippon Sumitomo Pharma Co., Ltd., Kowa Co., Ltd., MSD K.K.,
assessed in the present study. One report has suggested that Mitsubishi Tanabe Pharma Co., Nippon Boehringer Ingelheim Co.,
exercise has a benecial effect on endothelial function in patients Ltd., Novartis Pharma K.K., Otsuka Pharma Ltd., Pzer Japan Inc.,
with PAD [30]. This effect may prevent atherothrombotic events. Sano-Aventis K.K., Takeda Pharmaceutical Co., Ltd., and Teijin
In HD patients with a clinical diagnosis of PAD, treatment with Pharma Ltd. Department of Renal Replacement therapy is endowed
cilostazol improved long-term clinical outcomes including the by Baxter Co., Ltd.
prevention of both stroke and all-cause mortality. We believe that
administration of cilostazol may have a substantial potential for Acknowledgments
improving outcomes due to its effect in preventing atherosclerotic
events in HD patients. A large, prospective, randomized multi- None.
center study is needed to conrm our ndings.

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Please cite this article in press as: Ishii H, et al. Treatment with cilostazol improves clinical outcome after endovascular therapy in
hemodialysis patients with peripheral artery disease. J Cardiol (2015), http://dx.doi.org/10.1016/j.jjcc.2015.05.003
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Please cite this article in press as: Ishii H, et al. Treatment with cilostazol improves clinical outcome after endovascular therapy in
hemodialysis patients with peripheral artery disease. J Cardiol (2015), http://dx.doi.org/10.1016/j.jjcc.2015.05.003