J Cardiol 2003 Jul; 42（1）: 13 – 22

Preventive Effect of an Antiallergic
Drug, Pemirolast Potassium, on
Restenosis After Stent Placement:
Quantitative Coronary Angiography and Intravascular UltrasoundStudies
Hidefumi

OHSAWA, MD, FJCC

Hirofumi

NOIKE, MD

Masahito KANAI, MD
Takashi

HITSUMOTO, MD

Kaneyuki

AOYAGI, MD

Takeshi

SAKURAI, MD

YuhkohSUGIYAMA, MD

Kunio

YOSHINAGA, MD

Michihisa
Jun
Takuo

KAKU, MD
MATSUMOTO, MD
IIZUKA, MD

Kazuhiro SHIMIZU, MD
Mao

TAKAHASHI, MD

Takanobu

TOMARU, MD

Hiroshi

SAKURAGAWA,

MD
Abstract ─────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────
Objectives. The preventive effect of pemirolast against restenosis after coronary stent placement wasevaluated.
Methods. Eighty-four patients with 89 de novo lesions who underwent successful coronary stenting
were assigned to the pemirolast group（40 patients, 45 lesions）and the control group（44 patients, 44
lesions）. Administration of pemirolast（20 mg/day）was initiated from the next morning after stenting andcontinued for 6 months of follow-up. Quantitative coronary angiography was performed immediately after
stenting and at follow-up. Angiographic restenosis was defined as diameter stenosis ＞− 50% at follow-up.
Intravascular ultrasound study conducted at follow-up angiography was used to measure vessel cross-sectional area（CSA）, stent CSA, lumen CSA, neointima CSA（stent CSA − lumen CSA）, and percentage
neointima CSA（neointima CSA/stent CSA × 100%）at the minimal lumen site.
Results. There were no significant differences in baseline characteristics between the two groups.
Restenosis rate was significantly lower in the pemirolast group than in the control group（15.0% vs 34.1%
of patients, 13.3% vs 34.1% of lesions, p ＜ 0.05, respectively）. The intravascular ultrasound study at follow-up（36 lesions in the pemirolast group, 33 in the control group）found no significant differences in vessel CSA and stent CSA between the two groups（17.3 ± 2.2 vs 16.8 ± 2.4 mm2, 8.6 ± 1.9 vs 8.4 ±──────────────────────────────────────────────
東邦大学医学部付属佐倉病院 循環器センター : 〒 285−0841 千葉県佐倉市下志津 564−1
Cardiovascular Center, Sakura Hospital, Toho University School of Medicine, Chiba
Address for correspondence : OHSAWA H, MD, FJCC, Cardiovascular Center, Sakura Hospital, Toho University School of Medicine,
Shimoshizu 564−1, Sakura, Chiba 285−0841
Manuscript received November 15, 2002 ; revised January 8 and March 31, 2003 ; accepted March 31, 2003

13

14

Ohsawa, Noike, Kanai et al

1.7 mm2, respectively）. However, lumen CSA was significantly larger in the pemirolast group than in thecontrol group（5.5 ± 1.3 vs 4.4 ± 1.1 mm2, p ＜ 0.05）. Moreover, neointima CSA and percentage neointima
CSA were significantly smaller in the pemirolast group（3.1 ± 1.1 vs 4.0 ± 1.2 mm2, p ＜ 0.05 and 36.2 ±
15.9% vs 47.4 ± 15.6%, p ＜ 0.01）.
Conclusions. Pemirolast has a preventive effect against restenosis after stent placement, possibly byinhibiting neointimal hyperplasia.
───────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────J Cardiol 2003 Jul ; 42（1）
: 13−22

Key Words
Intravascular ultrasoundCoronary artery disease
Drug therapy pemirolast potassium
Stent

INTRODUCTION
Coronary restenosis remains a major limitationof percutaneous coronary intervention（PCI）and
has become a major complication in developed
countries. Stenting has reduced restenosis by preventing pathologic vascular remodeling1,2）, but the
proliferation of vascular smooth muscle cells, oneof the causes of restenosis, is commonly observed
after stent placement3）. Almost 80% of contemporary PCI procedures are performed with the use ofcoronary stents, so strategies aimed at eradicating
neointimal hyperplasia are a current focus ofresearch.
We previously found that pemirolast
potassium 4−8）, an antiallergic agent, markedly
inhibits migration and proliferation of vascularsmooth muscle cells9）. Pemirolast inhibits intimal
hyperplasia in animal experiments10）. Furthermore,
we recently confirmed that pemirolast prevents
coronary restenosis after plain old balloon angio11）
by the mechanism of inhibiting
plasty（POBA）
neointimal hyperplasia rather than pathologicalremodeling, as shown by angiographic andintravascular ultrasound（IVUS）studies12）.
The present clinical prospective randomized
study investigated the preventive effect of pemirolast on restenosis after coronary stent placement.
SUBJECTS AND METHODS
Study population
This study included 88 patients with symptomatic ischemic heart disease due to de novo lesionsof the native coronary artery treated between
January 1998 and March 1999. Patients with acute
myocardial ischemia, left ventricular ejection fraction of ＜− 40% or renal failure were excluded. The
angiographic criteria for exclusion were the presence of type C lesions13）such as chronic total occlusions（＞− 3 months old）, ostial lesions, left main

Prevention restenosis

trunk lesions, lesions in coronary vessels of＜ 2.5 mm caliber and diffuse lesions requiring 2 ormore stents. Coronary stenting was performed inpatients with suboptimal results such as dissection
or elastic recoil immediately after balloon angioplasty. The general exclusion criteria for stenting
were contraindications for anticoagulant andantiplatelet therapies.
Before the study, a through explanation wasgiven to patients and their families about the potential risks and benefits involved in this study, andwritten informed consent was obtained. The
patients were assigned to the group receiving
pemirolast（pemirolast group）, or the group notreceiving pemirolast（control group）by the prospective randomization technique.
Drug treatments
The pemirolast group received pemirolast（20 mg/day）, the standard dose as an antiallergic
drug, from the morning after stenting until followup angiography at 6 months. All patients in bothgroups received aspirin（162 mg/day）and ticlopidine（200 mg/day）from 1 week before the procedure until the time of follow-up angiography. Drugs
for treating complications such as hypertension,
hyperlipidemia, and diabetes mellitus were used at
the discretion of attending physicians, but the useof other antiallergic drugs was prohibited.
Stent implantation
Immediately before PCI, patients received an initial bolus injection of heparin（8,000 to 10,000 U）
and intracoronary administration of 200μg nitroglycerin. PCI was performed by POBA, followed
by implantation of stents. Either a slotted tube stent（Palmaz-Schatz）
or a coil stent（Wiktor or gfx）was
selected according to the lesion characteristics andcoronary vessel morphology. The Palmaz-Schatz
stent was placed either by the stent delivery system
J Cardiol 2003 Jul; 42（1）: 13 – 22

Effect of Pemirolast on In-Stent Restenosis

or was mounted on the balloon used for pre-dilation. After successful stent delivery, balloon dilation at high pressure was added to achieve the optimal result, which was defined as residual stenosisof less than 10% of the luminal diameter withoutcomplications（death, myocardial infarction, coronary artery bypass surgery）. Heparin and nitroglycerin infusions were continued for 24 hours after
stenting.
Follow-up
All treated patients were monitored for at least 6months. Adverse effects attributable to pemirolast
were monitored at fixed periods（1 day, 2 weeks, 1month, 3 months and 6 months after the procedure）
by interview as well as laboratory examinations.
IVUS measurements and follow-up coronary
angiography were conducted 6 months after stenting. If ischemic symptoms recurred within 6months after stenting, coronary angiography was
performed earlier. If no definite restenosis wasfound, follow-up angiography was repeated 6
months later.
Quantitative coronary angiography
Coronary angiograms obtained before, immediately after, and at 6 months after stenting, werereviewed by an unbiased angiographer without
knowledge of group randomization. For quantitative analysis, end-diastolic cine-frames were selected from the angiographic views demonstrating the
maximal degree of stenosis and were matched
before, immediately after and at follow-up. The
selected cine-frames were digitalized with a cinevideo converter, and were analyzed using a quantitative coronary angiography system（Heart analysis
database system, Medical Soft Support Center
Corp.）. The guiding and diagnostic catheters wereused as the calibration standard to measure the reference diameter, minimal lumen diameter and percentage diameter stenosis. Acute gain was definedas the increase in minimal lumen diameter immediately after stenting, late loss as the decrease in minimal lumen diameter at follow-up（post-procedureminimal lumen diameter minus follow-up minimal
lumen diameter）, and net gain as the difference
between acute gain and late loss. The loss index
was the ratio of late loss to acute gain.
Angiographic restenosis was defined as stenosis
of ＞− 50% diameter at the end of follow-up.

J Cardiol 2003 Jul; 42（1）: 13 – 22

15

Quantitative intravascular ultrasound
IVUS study was performed at follow-up angiography. IVUS examinations were performed with a30-MHz, 3.2 F mechanical ultrasound catheter（Boston Scientific, UltraCross）and were always
preceded by intracoronary administration of nitroglycerin（ 0.1 mg）. The IVUS catheter wasadvanced distal to the stenting site and then was
manually pulled back. The ultrasound images wererecorded onto super-VHS videotape for off-line
analysis, with a detailed running audio commentary
describing the location of the ongoing IVUS interrogation. Moreover, some angiographic images
were recorded during pullback so that the locationof the IVUS transducer was known.
Angiographic and IVUS data were analyzed side
by side. First, stent cross-sectional area（ CSA）,
lumen CSA, neointima CSA（stent CSA − lumen
CSA）and percentage neointima CSA（neointima
CSA/stent CSA × 100%）were measured on across-sectional image with the minimal lumen（Fig.
1）. Second, the mean data of these parameters were
calculated and were compared between the pemirolast group and the control group.
Statistical analysis
Student s t-test was used to assess differences incontinuous variables between the two groups. The
results are expressed as mean ± SD. Categoricalvariables, which are presented as rates, were compared by the chi-square test. Statistical significancewas defined as p ＜ 0.05.
RESULTS
Four of the 88 patients were excluded because ofdeviation from the protocol（2 patients in thepemirolast group）, or lack of follow-up angiography（1 patient in each group）. During follow-up,
neither symptoms nor significant aggravation oflaboratory findings attributable to pemirolast wereobserved in the pemirolast group. Thus, the final
angiographic study group contained 84 patients（89
lesions）, with 40 patients（ 45 lesions）in thepemirolast group and 44 patients（44 lesions）in thecontrol group. Baseline clinical characteristics areshown in Table 1, and baseline angiographic andprocedure-related characteristics are shown in
Table 2. There were no significant differences inbaseline characteristics between the two groups.

16

Ohsawa, Noike, Kanai et al

acute gain between the two groups. At follow-up,
the pemirolast group had a smaller mean reduction
in minimal lumen diameter（ late loss : 0.75 ±0.74 vs 1.17 ± 0.92 mm, loss index : 0.33 ± 0.29 vs0.52 ± 0.36, p ＜ 0.05, respectively）and larger net
gain（1.50 ± 0.72 vs 1.03 ± 0.83 mm, p ＜ 0.05）,
resulting in a larger minimal lumen diameter（ 2.11 ± 0.72 vs 1.68 ± 0.90 mm, p ＜ 0.05）.
Restenosis rates were significantly lower in thepemirolast group than in the control group（patients : 15.0% vs 34.1%, lesions : 13.3% vs34.1%, p ＜ 0.05, respectively）. In patients,
restenosis of the Palmaz-Schatz stent in the pemirolast group was as low as 9.1%. There were no significant differences in the incidence of target lesion
revascularization between the two groups（11.1% vs27.3%）.

Fig. 1 Quantitative intravascular ultrasound measurements at follow-up
Case A（46-year-old, male, pemirolast group）: PalmazSchatz stent φ 3.0 mm.
A-1 : Mild neointimal hyperplasia（no restenosis）.
A-2 : Stent CSA : 7.3 mm2, lumen CSA : 5.7 mm2,
percentage neointima CSA : 21.9%.
Case B（53-year-old, male, control group）: PalmazSchatz stent φ 3.5 mm.
B-1 : Moderate neointimal hyperplasia（no restenosis）.
B-2 : Stent CSA : 9.3 mm2, lumen CSA : 5.3 mm2,
percentage neointima CSA : 43.0%.
Case C（61-year-old, female, control group）: PalmazSchatz stent φ 3.5 mm.
C-1 : Severe neointimal hyperplasia（restenosis）.
C-2 : Stent CSA : 9.5 mm2, lumen CSA : 1.6 mm2,
percentage neointima CSA : 83.2%.
CSA ＝ cross-sectional area.

Intravascular ultrasound results
Twenty of the lesions investigated by follow-up
angiography were not investigated by IVUS for thefollowing reasons : The IVUS catheter failed tocross either at proximal or stenting sites because ofproximal bend point or severe restenosis in 17
lesions（pemirolast group : 8, control group : 9）,and the risk of IVUS study was too great in 3
lesions（pemirolast group : 1, control group : 2）.
Thus the IVUS study group contained 69 lesions,
36 lesions（restenosis in 4）
in the pemirolast groupand 33 lesions（restenosis in 9）in the control group.
Vessel CSA（pemirolast group : 17.3 ± 2.2 vscontrol group : 16.8 ± 2.4 mm 2）and stent CSA（8.6 ± 1.9 vs 8.4 ± 1.7 mm 2）showed no differences between the two groups. Lumen CSA wassignificantly larger in the pemirolast group than in
the control group（5.5 ± 1.3 vs 4.4 ± 1.1 mm2, p ＜0.05）. Moreover, neointima CSA and percentage
neointima CSA were significantly smaller in thepemirolast group（ neointima CSA : 3.1 ± 1.1 vs
4.0 ± 1.2 mm 2, p ＜ 0.05, percentage neointima
CSA : 36.2 ± 15.9% vs 47.4 ± 15.6%, p ＜ 0.01 ;Fig. 2）.
DISCUSSION

Angiographic results
Luminal dimensions at baseline, immediately
after stenting, and at follow-up are shown in Table
3. There were no differences between the twogroups in baseline reference diameter and minimal
lumen diameter. Immediately after stenting, there
were no differences in minimal lumen diameter and

The techniques of PCI have changed from early
POBA to more recent stenting, which can eliminate
acute coronary occlusion and negative vascularremodeling. However, in-stent restenosis remains
unresolved. In recent years, IVUS studies to examine the restenosis process following stent placement
have determined that neointimal hyperplasia is
J Cardiol 2003 Jul; 42（1）: 13 – 22

Effect of Pemirolast on In-Stent Restenosis

Table 1 Patient characteristics
Pemirolast group

Control group

Number of patients

40

44

Male sex
（%）

65.0

72.7

NS

Age（yr, mean±SD）65.4±9.0

63.9±10.0

NS

Hyperlipidemia（%）

55.0

56.8

Hypertension
（%）

60.0

52.3

Current smoker（%）

37.5

43.2

（%）
Obesity（body mass index＞24）

17.5

22.7

Diabetes mellitus（%）

32.5

22.7

Hyperuricemia（%）

17.5

20.5

Prior myocardial infarction
（%）

20.0

22.7

NS

Unstable angina（%）

32.5

27.3

NS

−

p valueNS

Concomitant drugs（%）
Aspirin and ticlopidine

100

100

Nitrates

92.5

93.2

Calcium antagonists

82.5

88.6

Beta blockers

42.5

50.0

Angiotensin converting enzyme inhibitors

27.5

20.5

Lipid lowering drugs（simvastatin or pravastain）

25.0

20.5

NS

Table 2 Angiographic and procedure-related characteristics
p value

Pemirolast group

Control group

45

44

Left anterior descending artery

53.3

50.0

Left circumflex artery

17.8

20.5

Right coronary artery

28.9

29.5

Type A

22.2

18.2

Type B1

44.5

54.5

Type B2

33.3

27.3

Lesion length（mm）

11.3±4.2

10.9±4.2

Palmaz-Schatz

48.9

59.2

Wiktor

28.8

20.4

gfx

22.2

20.4

Single stent

87.5

100

Multiple stents

12.5

0

Final balloon/artery ratio

1.10±0.1

1.07±0.1

NS

Final balloon pressure（atm）

12.9±2.513.4±2.8

NS

Number of lesions
Target vessel（%）

NS

Modified ACC/AHA class（%）
NS
NS

Type of stents（%）
NS

Number of stents per patient（%）

Continuous values are mean±SD.
ACC/AHA＝American College Cardiology/American Heart Association.

J Cardiol 2003 Jul; 42（1）: 13 – 22

NS

17

18

Ohsawa, Noike, Kanai et al

Table 3 Quantitative coronary angiographic analysis
Pemirolast group
Number of lesions

Control groupp value45443.01±0.42

3.03±0.25

NSPre stent

0.61±0.28

0.65±0.34

NS

Post stent2.86±0.28

2.93±0.25

NS
＜0.05

Reference diameter（mm）
Minimal luminal diameter（mm）

Follow-up

2.11±0.72

1.68±0.90

Acute gain（mm）

2.25±0.38

2.28±0.39

NS

Late loss（mm）

0.75±0.74

1.17±0.92＜0.05

Net gain（mm）

1.50±0.72

1.03±0.83＜0.05

Loss index

0.33±0.29

0.52±0.36＜0.05

Patient restenosis（% of patients）

6/40（15.0）

15/44（34.1）＜0.05

Lesion restenosis（% of lesions）

6/45（13.3）

15/44（34.1）＜0.05

Tube stent（Palmaz-Schatz）

2/22（ 9.1）

8/26（30.8）

0.06

Coil stent（Wiktor or gfx）

4/23
（17.4）

7/18（38.9）

NS

5/45（11.1）

12/44（27.3）NS

Target lesion revascularization（% of lesions）
Continuous values are mean±SD.（）: %.

Fig. 2 Quantitative intravascular ultrasound analysis of a cross-sectional image with the minimal
lumen area at follow-up
Abbreviation as in Fig. 1.

solely responsible for in-stent restenosis 3,14）.
Moreover, intimal hyperplasia is more common
after stenting than POBA. Therefore, neointimal
hyperplasia, or proliferation of vascular smoothmuscle cells, must be prevented to avoid in-stentrestenosis.
Previously, we confirmed by molecular biology
study that the antiallergic agent, pemirolast,markedly inhibits vascular smooth muscle cell proliferation induced by platelet-derived growth factor,
angiotensin Ⅱ or endothelin Ⅰ. In addition, we
found that pemirolast suppresses membrane inositol
phospholipid turnover at an early stage of the intracellular signal-transduction system, suggesting that
this is one of the mechanisms by which the agent
inhibits vascular smooth muscle cell proliferation9）.
J Cardiol 2003 Jul; 42（1）: 13 – 22

Effect of Pemirolast on In-Stent Restenosis

Furthermore, our prospective randomized comparative study found that pemirolast reduces not only
the angiographic restenosis rate but also late cardiac events after POBA11）. In addition, our IVUS
study showed that pemirolast does not prevent vascular remodeling but does prevent neointimal
hyperplasia in patients treated with POBA12）. These
results suggest that pemirolast has pharmacologicalproperties useful in preventing restenosis following
PCI. Consequently, concomitant therapy by stenting with pemirolast may be more useful for preventing restenosis.
In the present study, the in-stent restenosis rate in
the control group was 34.1%（Palmaz-Schatz stent :30.8%, coil stent : 38.9%）, which was slightly
higher compared with the results of the BENESTENT1）and STRESS2）（22% and 31.6%）. In ourstudy, 41% of lesions were treated with coil stents,
whereas only the Palmaz-Schatz stent was used in
the BENESTENT and STRESS. On the other hand,
the in-stent restenosis rate of the pemirolast groupwas 13.3%（Palmaz-Schatz stent : 9.1%, coil stent :17.4%）, which was significantly lower than that ofcontrol group（ 13.3% vs 34.1%）. These angiographic results strongly suggested the preventive
effect of pemirolast against restenosis. Moreover,the IVUS study found no difference in vessel areaor stent area at the follow-up stage between the twogroups. However, the lumen area was significantly
larger, and the neointima area and percentage
neointima area were significantly smaller in thepemirolast group. These results suggest thatpemirolast has clinical effectiveness to inhibit the
proliferation of vascular smooth muscle cells.
The exact mechanisms by which pemirolast
inhibits vascular smooth muscle cell proliferation
after stenting are not known. In-stent restenoses
result from excessive fibroproliferative and inflammatory responses to insults to the arterial wall15,16）.
Growth factors, cytokines and vasoregulatory molecules trigger the proliferation of vascular smoothmuscle cells 17） . In-stent lesions containmacrophages, histiocytes, eosinophils and T lymphocytes15,16）. Immunocomponent cells are predominantly detected around stent struts, which suggests
a local immune response and inflammatory reaction
to foreign material15）. Therefore, the inflammatory
response and development of restenosis may be
increased by a contact-allergic reaction to metalcompounds released from stainless-steel stents.
Recently, a delayed hypersensitivity reaction to
J Cardiol 2003 Jul; 42（1）: 13 – 22

19

nickel and molybdenum was proposed as a triggering factor in in-stent restenosis 18）. Therefore,
pemirolast may inhibit this contact-allergic reaction
to metal compounds released from stainless-steel
stents. However, the mechanism still remains unexplained, since the association between allergic reactions to stent components and the occurrence of instent restenosis was not investigated in our study. If
this hypothesis is correct, preprocedural administration of pemirolast may be likely to be more effective than postprocedural administration. Anotherpossibility is that pemirolast may inhibit the activity of mast cells which secrete an angiotensin Ⅱforming enzyme, namely chymase 19− 21） .
Experimental studies have shown that angiotensin
Ⅱ promotes the proliferation of vascular smoothmuscle cells and extracellular matrix22,23）. Injury to
the intima of the carotid artery in dogs leads to anincrease in the number of mast cells in the adventitia and fibrotic outgrowth as well as intimal hyperplasia. Moreover, an increase in angiotensin Ⅱ level
and a chymase level exceeding the angiotensinconverting enzyme level were demonstrated in the
injured vascular wall21）. Accordingly, further studies should be performed to elucidate the effects of
pemirolast on the chymase-dependent angiotensin
Ⅱ-forming pathway.
Before our study, the results of small placebocontrolled angiographic trials showed a statisticallyand clinically significant reduction in restenosis
after POBA with tranilast24,25）, which is an antiallergic and antikeloid drug. In a concurrent controlled study, patients who were treated with only
stent placement were compared with those who
received concomitant therapy by stenting and tranilast, showing a reduction in angiographic restenosis
26）
from 45% to 26%（p ＜ 0.05）. These trials werelimited in scope and could not demonstrate statistical differences in clinical outcomes. Therefore, thePrevention of REStenosis with Tranilast and its
Outcomes（PRESTO）trial was conducted to evaluate the effects of tranilast on major adverse cardiovascular events as well as quantitative angiographic
and IVUS end points. However, this multicenter,large, randomized clinical trial, found that administration of tranilast in 2 different doses for 2 different durations was associated with no improvementin either angiographic or clinical restenosis compared with administration of placebo27）. Although
we found that pemirolast more strongly inhibits theproliferation of vascular smooth muscle cells com-20

Ohsawa, Noike, Kanai et al

pared with tranilast（unpublished data）, the differences in mechanisms or potential for preventing instent restenosis between pemirolast and tranilast
still remain unknown.
In recent years, many studies have examined theprevention of restenosis by using drugs. The polymer coated stent has been developed as a stentbased pharmacologic strategy which could be
effective to increase the biocompatibility of metal
stents to human body as well as enable local delivery of drugs. Drug-eluting stents, which could
maintain an effective drug concentration in the target tissue over a certain period of time, were also
developed and are currently under investigation.
Clinical studies of stents eluting sirolimus（rapamycin）or paclitaxel are already underway inEurope and U.S., and the effectiveness will soon be
known28,29）. The pemirolast-eluting stent will also
be investigated in more detail.

lesions which were subjected to angiographic
analysis at follow-up could not be included in the
IVUS study, so the patients with the worst results
such as severe restenosis at follow-up were excluded, and the effects of pemirolast might not be completely assessed. This IVUS study was recorded bymanual pullback method of IVUS catheter, and was
a comparative study of the neointima area at only
the minimal lumen with two-dimensional IVUS, so
the neointima hyperplasia measurement might not
be accurate. Therefore, a comparative study to
examine in-stent neointima volume using the auto
pullback method and three-dimensional IVUS isnecessary. All of the stents used in this study werefrom the first generation, so further study to examine whether pemirolast can lower the risk ofrestenosis in patients treated by current stents is
expected.

Study limitations
This study has a few important limitations. The
major limitations are the small number of patientsin each group and the open-label study design.
Therefore, a double-blind study with a large number of patients is needed. Twenty（22%）of all 89

The results of the present randomized comparative study suggest that the administration of
pemirolast inhibits vascular smooth muscle cellproliferation after coronary stenting, and is usefulin the clinical setting to prevent in-stent restenosis.

要

CONCLUSIONS

約

抗アレルギー薬であるペミロラストのステント再狭窄に及ぼす予防効果:
定量的冠動脈造影と血管内エコー法による検討

背

大澤

秀文

野池

博文

金井

正仁

櫃本

孝志

青柳

兼之

櫻井

岳史

杉山

祐公

吉永

国士

賀来美千久

松 本

淳

飯塚

卓夫

清水

一寛

高橋

東丸

貴信

櫻 川

浩

徳弘

圭一

真生

景 : 我々は抗アレルギー薬であるペミロラストカリウムが内膜増殖抑制作用により経皮的冠動脈拡張術後の再狭窄を減少させることを報告したが，ステント再狭窄に関する有効性についてはいまだ不明である．
目的 : ペミロラストがステント再狭窄を予防するか否かを明らかにする．

方法 : 初回待機的ステント留置術の成功 84 例を無作為にペミロラスト投与群（ペミロラスト群 :40 例，45 病変）と対照群（44 例，44 病変）に振り分け，ペミロラスト群には術翌朝よりペミロラス
ト 20 mg/day の経口投与した．定量的冠動脈造影はステント直後および 6 ヵ月後に行い，再狭窄の
定義は 6 ヵ月後の定量的冠動脈造影で狭窄度が 50% 以上とした．血管内エコー法は 6 ヵ月後に行い，ステント内の最小血管内腔部における血管断面積（VA），血管内腔面積（LA），ステント面積（SA），
新生内膜面積（NA ＝ SA − LA），%NA［（SA − LA）/SA × 100］を計測・算出し，これらの指標の平均値を 2 群間（ペミロラスト群 : 38 病変，対照群 : 33 病変）で比較検討した．
結果 : 両群間に患者，病変，手技背景に差異はなかった．患者および病変再狭窄率はペミロラ
J Cardiol 2003 Jul; 42（1）: 13 – 22

Effect of Pemirolast on In-Stent Restenosis

21

スト群が対照群に比べて有意に低率であった（15.0% vs 34.1%，13.3% vs 34.1%，各 p ＜ 0.05）．血管内エコー法では，遠隔期の VA および SA はともに両群間で差異を認めなかったが（17.3 ± 2.2 vs16.8 ± 2.4 mm2，8.6 ± 1.9 vs 8.4 ± 1.7 mm2），NA および %NA はペミロラスト群が対照群に比べて有，意に小さく（NA : 3.1 ± 1.1 vs 4.0 ± 1.2 mm2，p ＜ 0.05 ; %NA : 36.2 ± 15.9% vs 47.4 ± 15.6%，p ＜ 0.01）
それに伴い遠隔期の LA はペミロラスト群で有意に大であった（5.5 ± 1.3 vs 4.4 ± 1.1 mm 2，p ＜0.05）．
結語 : ペミロラストは新生内膜増殖を抑制することによりステント後再狭窄を予防することが示唆された．

J Cardiol 2003 Jul; 42（1）: 13−22

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