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(Circulation. 1996;93:215-222.)
© 1996 American Heart Association, Inc.
Articles |
A Randomized Comparison of Combined Ticlopidine and Aspirin Therapy Versus Aspirin Therapy Alone After Successful Intravascular Ultrasound–Guided Stent Implantation
Presented in part at the 67th Scientific Sessions of the American Heart Association, Dallas, Tex, November 14-17, 1994, and published in abstract form in Circulation (1994;90[pt 2]:I-124).
From Centro Cuore Columbus, Milan, Italy, and Toho University Ohashi Hospital, Third Department of Internal Medicine (S.N.), Tokyo, Japan.
Correspondence to Antonio Colombo, MD, Centro Coure Columbus, Via M Buonarotti 48, Milan 20145, Italy.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Background Previous studies have shown that it is feasible to withhold anticoagulation after a successful intracoronary stent procedure with a low incidence of stent thrombosis. The importance of specific antiplatelet agents when stenting is performed without anticoagulation is unknown.
Methods and Results After successful intravascular ultrasound–guided stenting, 226 patients were randomly assigned to receive either aspirin therapy alone (n=103) or a combination of ticlopidine and short-term aspirin therapy (n=123). Primary angiographic and clinical end points were stent thrombosis, death, myocardial infarction, the need for postprocedure coronary artery bypass surgery or repeated angioplasty, and significant medication side effects requiring termination of the medication within the first month of a successful procedure. At 1 month, the rate of stent thrombosis was 2.9% in the aspirin only group and 0.8% in the ticlopidine-aspirin group (P=.2). Cumulative major clinical events after successful stenting occurred in 3.9% of the patients in the aspirin group and in 0.8% in the ticlopidine-aspirin group (P=.1). There were no medication side effects in the aspirin group; in the combined ticlopidine-aspirin group, medication side effects occurred in 3 patients (P=.2).
Conclusions At 1 month, there was no difference in the incidence of stent thrombosis or other clinical end points between the two poststent antiplatelet regimens. However, the relatively small size of the study and the low incidence of thrombosis events may have contributed to the failure to detect differences in angiographic and clinical end points between the two groups.
Key Words: stents • ultrasonics
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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An era of increasingly widespread use of intracoronary stents for the treatment of coronary artery lesions is just beginning, after a long process of scientific investigation. Even with the proven benefits of intracoronary stent implantation, bleeding complications from a stringent anticoagulation regimen impose significant practical and economic limitations to increased clinical use and have not eliminated stent thrombosis.1 2 3 4 Although it is generally accepted that all metallic stents have thrombogenic potential, the incidence of stent thrombosis has generally decreased as operators have become more experienced and the stent technique has improved.1 2 3 4 5 6 7 8 The use of intravascular ultrasound evaluation after stent implantation provided clear evidence that stent underexpansion was a principal cause of stent thrombosis.9 10 In a subsequent prospective trial of 321 consecutive patients undergoing intravascular ultrasound–guided Palmaz-Schatz stent implantation, the incidence of stent thrombosis within the first month was 0.9% in patients receiving only antiplatelet therapy (ticlopidine 250 mg BID for 1 to 2 months with short-term aspirin 325 mg/d or aspirin 325 mg/d alone) after a successful procedure. Improvement in stent expansion was achieved by use of either higher pressures or larger balloons.9 10 11 12
Using similar techniques for final stent optimization, other European investigators have reported on the safety of stent implantation performed without subsequent warfarin and without intravascular ultrasound guidance.13 14 15 16 17 18 19 20 21 22 Stent thrombosis rates of 0% to 2% have been reported with either ticlopidine alone or ticlopidine-aspirin therapy after a successful stent procedure. The results have stimulated the increasingly common usage of ticlopidine after stent implantation procedures despite the increased risk of leukopenia that occurs in up to 2% to 2.5% of patients treated with ticlopidine. Despite the encouraging results and low thrombosis rates achievable with ticlopidine-based therapy after successful stent implantation, the clinical superiority in efficacy of ticlopidine over aspirin therapy in the prevention of stent thrombosis has never been proved. Therefore, we conducted a randomized study comparing the safety and efficacy of ticlopidine with short-term aspirin and aspirin alone after a successful intravascular ultrasound–guided stent implantation procedure.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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From January 1994 through March 1995, 226 patients with 294 lesions were enrolled in this randomized study. During the study, 541 coronary interventions were performed. Stent deployment was attempted in 358 patients (66%), coronary angioplasty was performed in 176 patients (33%), and 7 patients (1%) underwent either directional atherectomy or rotational ablation procedures. There were 132 patients (37%) who underwent attempted stent implantation who were not enrolled in the study. The reasons for exclusion were an unsuccessful procedure (14 patients), a suboptimal result believed to require anticoagulation (13 patients), treatment with an antiplatelet agent other than aspirin or ticlopidine (4 patients), enrollment in a stent trial that required the use of anticoagulation after stent implantation (5 patients), and the need for treatment with warfarin for other medical reasons (3 patients). During the course of the study, 84 patients (23% of the total stent volume) also had successful intravascular ultrasound–guided stent implantation and were treated with ticlopidine-aspirin or aspirin alone after the procedure who either did not consent to enrollment in the study or were treated according to the preference of the referring physician.
Entry criteria included coronary artery disease manifested by clinical symptoms or objective evidence of myocardial ischemia either on exercise test or by nuclear scintigraphy and angiographic evidence of single-vessel or multivessel coronary disease with target lesion stenosis >70% by visual estimate. Exclusion criteria included small vessels (<2.5 mm by visual estimate) and angiographically diffuse distal disease that might compromise outflow after stent insertion. Patients who were allergic to aspirin, were taking ticlopidine or other nonaspirin antiplatelet agents before the procedure, or required warfarin for other medical reasons also were excluded. The study required completion of a successful intravascular ultrasound–guided stent implantation procedure. Patients with suboptimal results at the end of the stent procedure owing to stent underexpansion, inability to adequately cover dissections, or residual lesions adjacent to the stent were treated with a standard anticoagulation regimen consisting of heparin and warfarin and were excluded from study enrollment.
Stent Implantation Procedure
Patients received aspirin 325 mg
and calcium channel
antagonists before stent deployment. A bolus of 10 000 U
heparin was given after sheath insertion, with an additional bolus of
5000 U given as needed to maintain the activated clotted time
to >250 seconds. Patients were not given dextran or dipyridamole
before, during, or after the stent procedure. Ticlopidine was not
administered before or during the stent procedure. Six different types
of stents were used during this study: the Palmaz-Schatz stent (Johnson
and Johnson Interventional Systems Co), the Gianturco-Roubin stent
(Cook Cardiology, Cook, Inc), the Wiktor stent
(Medtronic, Inc), the Micro stent (Applied Vascular Engineering), the
Wall stent (Schneider Inc), and the Cordis stent (Cordis Corp). After
predilation or balloon angioplasty, stents were delivered with standard
guidelines. The majority of the Palmaz-Schatz stents deployed were bare
stents inserted with previously described
techniques.12 23
After deployment of all stents, further dilations were performed with
noncompliant balloons (for the Palmaz-Schatz and Wall stents) or
minimally compliant balloons (for all coiled stents). After the
angiographic result was considered acceptable, intravascular ultrasound
was performed. All subsequent treatment decisions were based on the
ultrasound results in conjunction with angiographic assessment, as
described later. Further balloon dilation or stent implantation was
performed to achieve an acceptable ultrasound result.
Stent implantation was performed electively, for suboptimal results, for restenosis after previous angioplasty, for the treatment of chronic occlusions, and for threatened or acute closure by standard definitions.12 Emergency stent implantation was considered stent deployment performed for acute or threatened closure. Multiple stents were defined as the use of more than one stent per lesion or patient. For the purpose of counting the number of each type of stent, each stent was counted as one stent. For calculating the mean number of stents per lesion or patient, the short Palmaz-Schatz stents and 4 or 8 mm Micro stents were counted as half stents; all other stents were counted as one stent.
Intravascular Ultrasound Equipment and Measurements
Coronary
arteries were imaged with a 2.9F or 3.2F
monorail system with a 30-MHz transducer-tipped catheter
(Cardiovascular Imaging System). Validation of
quantitative measurements, pathological correlation with ultrasound
measurements, and intraobserver and interobserver reproducibilities
were reported previously.12 24 Images were obtained
with a
manual or an automated pullback system. The position of the catheter on
fluoroscopy was used to correlate the ultrasound image with the
angiogram. Data were stored on 0.5-in super VHS videotape. On-line
quantitative measurements were performed during the procedure. The
ultrasound catheter was advanced distal to the stent, and images were
recorded while the imaging catheter was pulled slowly through the
stented segment. Measurements were made at the proximal or distal
reference sites (generally, within 5 to 10 mm of the stented segment)
of the vessel cross-sectional area (CSA), vessel minor and major
diameters, lumen CSA, and lumen minor and major diameters. The
reference site measurements were made at sites that did not appear
severely diseased on intravascular ultrasound image and that had
minimal balloon trauma from prior balloon dilation. The vessel border
(as distinguished from the lumen) was defined on the ultrasound image
as the outer boundary of the echo-lucent media surrounding the
plaque. Lumen measurements were made at the inner border of the
echo-dense plaque. Intrastent lumen CSA and diameter measurements
were made at the tightest position within the stent. The average of the
proximal and distal vessel CSAs was used to estimate the vessel
dimensions of the stented segment because intense echo reverberations
from the metallic struts frequently prevented measurements of the
vessel boundary beyond the stent. Intravascular ultrasound imaging was
performed in the reference sites and the stented segment at the initial
intravascular ultrasound evaluation and after each series of balloon
dilations. Measurements were made at the tightest point within the
stented segment after each series of balloon dilations. The
measurements at the reference site were done on the initial
intravascular ultrasound evaluation to minimize the potential balloon
dilation effect that might increase the dimensions of the reference
site.
Intravascular Ultrasound Criteria for Optimal Stent
Expansion
The criteria for optimal stent expansion were governed by
the
principles of optimizing stent expansion and covering the full extent
of the lesion to minimize any potential impairment to flow that could
contribute to stent thrombosis. The first criterion was a qualitative
evaluation of the stent site involving the achievement of good stent
apposition to the vessel wall with good plaque compression. The
quantitative criterion for stent expansion used was the achievement of
an intrastent lumen CSA (at the tightest measured point) that was 80%
of the distal reference lumen CSA. In smaller vessels in which the
lesions had a measured CSA of <7.5 mm2, this
quantitative criterion was modified slightly so that it was the
achievement of stent lumen greater than the distal lumen CSA. This was
done to account for the higher risk of partial obstructions in the
stented segments in smaller vessels compared with larger vessels.
Critical lesions in adjacent unstented segments, particularly
dissections extending to the media as identified on ultrasound
evaluation, were treated by additional stent implantation.
Angiographic Analysis
Coronary angiograms were analyzed
without
knowledge of the intravascular ultrasound data by experienced
angiographers not involved in the stenting procedure. Patients received
intracoronary nitroglycerin before baseline
and final angiograms to achieve maximal vasodilation. To optimize
reproducibility, the position of the radiogram gantry was recorded
in all views at the time of the baseline angiograms, and final
angiograms were performed in matching views. Angiographic measurements
were performed during diastole. The lesions were measured
from an optically magnified image in a single, matched "worst"
view with digital calipers (Brown and Sharp). The guiding catheter was
used as the reference object for magnification calibration. Previous
studies have shown that digital calipers correlate closely with
computer-assisted methods with low interobserver and intraobserver
variabilities.25 26 Minimal lumen diameter and
percent
diameter stenosis were obtained on the baseline and final
angiograms. The diameters of the proximal and distal lumen reference
sites were averaged to obtain a mean reference diameter. The average
reference diameter was used to calculate the percent diameter
stenosis at baseline and final angiograms. The average
reference diameter was used for these calculations to have a
correlation with the proximal and distal measurements performed on
intravascular ultrasound and because the average reference vessel was
thought to be a better reflection of the vessel size when multiple
stents were placed in long segments of various diameters. Lesion length
was measured on baseline angiography from the point at which the lumen
was compromised by 50% at the proximal or distal reference vessel
site. Lesions were characterized according to the modified American
College of Cardiology–American Heart Association
score.27 The distance between lesions in the same vessel
was measured. Long lesions were defined as a single continuous
narrowing >15 mm. The presence of thrombus, defined as a filling
defect seen in multiple projections surrounded by contrast in the
absence of calcification, was noted at baseline or during the
procedure. Thrombolysis in Myocardial Infarction (TIMI)
grade flow was recorded at the time of the initial procedure to
characterize the indication for stenting as previously
described.28
Postprocedure Medication Protocol
If the intravascular
ultrasound criteria for optimal stent
expansion were met and the angiographic result was acceptable, no
further heparin was administered, and sheaths were removed in 4 to 6
hours. When procedures were performed in the evening, heparin was
infused overnight, and the sheaths were removed the following morning.
After a successful procedure, patients were randomized to receive
either ticlopidine 250 mg BID for 1 month with short-term aspirin
325 mg for 5 days or aspirin 325 mg/d. After 1 month of treatment by an
assigned antiplatelet regimen, the patients received a
standardized treatment with 325 mg/d indefinitely. Ticlopidine was
given for a single month because this is the time period for assessing
the risk of stent thrombosis and limiting the potential for adverse
side effects. The randomization was performed with a standard list of
random numbers. The administration of the antiplatelet agents
was open label; the physicians and patients were not blinded.
Events and Follow-up
This study was a randomized comparison
of poststent treatment
with two different antiplatelet regimens. Accordingly, a
comparison of clinical events and medication side effects within the
first month after a successful stent procedure between the combined
ticlopidine-aspirin and aspirin only groups was performed. An
assessment of complications at 1 month was performed because this is
the standard time period for evaluating stent thrombosis; it also was
the duration of treatment with ticlopidine. Major clinical events were
death, emergency bypass surgery, elective bypass surgery, myocardial
infarction (Q wave or non–Q wave), emergency repeated intervention
(bailout stenting or repeated angioplasty), and vascular complications.
Specific major event definition was death regardless of cause. A
diagnosis of Q-wave myocardial infarction was made when there was the
documentation of new pathological Q waves (
0.14 seconds) on an ECG in
conjunction with elevation of creatine kinase to more than twice the
upper limit of normal. Non–Q-wave myocardial infarction was defined as
elevation of the cardiac enzymes to more than twice the upper limit of
normal without the development of new pathological Q waves. Emergency
coronary bypass surgery was defined as bypass surgery involving
immediate transfer of the patient from the
catheterization laboratory to the operating room.
Elective coronary bypass surgery was nonemergency bypass
surgery performed >24 hours after a stent procedure for procedural
failure in the absence of ischemia or evolving myocardial
infarction. Acute thrombosis events were defined as angiographically
documented occlusion with TIMI grade 0 flow at the stent site within 24
hours of the stent procedure. Subacute thrombosis events were
angiographically documented occlusions with TIMI grade 0 flow at the
stent site >24 hours after the stent procedure. Unexplained sudden
death in the first month after a stent implantation procedure was
considered a stent thrombosis event. Emergency intervention included
bailout stenting or emergency angioplasty performed for ongoing acute
ischemia or evolving myocardial infarction in the setting of an
angiographically documented stent thrombosis event. Vascular
complications were defined as the occurrence of bleeding or hematoma
formation at the access site that required transfusion, vascular
repair, or external compression. Medication side effects also were
recorded.
After a successful procedure, patients were generally discharged from the hospital within 1 to 2 days. Clinical follow-up was performed by telephone contact of all patients within 1 to 4 months of hospital discharge. The short-term complications (stent thrombosis) continued to be assessed carefully through regular and uniform contact of all patients within 4 weeks of hospital discharge and 2 months later.
Statistical Analysis
The primary clinical analysis consisted
of a comparison
of the major clinical events and medication side effects at 1 month
between the two study groups. Normally distributed data are expressed
as mean±SD. Data that were not normally distributed are expressed as a
median with a range of values. Comparisons between equivalent groups
were performed by a two-tailed t test. Comparisons of
discrete variables were made by 
2
analysis. Differences were considered statistically significant
at P<.05.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Patient Characteristics
After appropriate consent was obtained, a total of 226 patients were randomly assigned to either ticlopidine with short-term aspirin (n=123, 163 lesions) or aspirin alone (n=103, 131 lesions) after successful intravascular ultrasound–guided stent implantation. A higher percentage of patients had prior coronary artery bypass or diabetes in the ticlopidine-aspirin group compared with the aspirin only group. Otherwise, there were no significant differences in the baseline characteristics of the two groups (Table 1
). As Table
2 shows, the baseline angiographic characteristics
between the two groups were similar, except the incidence of total
occlusions at baseline angiography was higher in the aspirin group
(15%) than in the ticlopidine-aspirin group (8%,
P<.05). The indication for stent implantation and the type
and number of stents deployed in the two groups also were similar
(Table 3).
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Postprocedure Clinical Outcome at 1 Month
There were no acute
stent thrombosis events in either of the two
antiplatelet treatment groups (Table 4). At the
1-month clinical follow-up, the subacute stent thrombosis rates
were not significantly different in the two groups (P=.2).
The incidence of angiographically documented stent thrombosis in the
ticlopidine-aspirin group was 0.8%, with the single event
occurring 12 days after stent implantation. Three stent thrombosis
events (2.8%) occurred in the aspirin only group. The stent thrombosis
events were angiographically documented in two patients on days 5 and
10 after the stent implantation procedure; the third was presumed to be
a stent thrombosis event after the patient died suddenly 20 days after
stent implantation. This was a witnessed death that occurred without
prodrome of chest pain in a patient with no antecedent history of
ventricular arrhythmias. There was no difference in
the major clinical events that occurred the first month after stent
implantation between the two groups. Although there was no significant
difference in the mortality rates between the two groups, it is
noteworthy that each of the stent thrombosis events in the aspirin only
group resulted in death (2.8%). In contrast, there were no deaths in
the ticlopidine-aspirin group in the 1-month follow-up
period.
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One vascular complication required surgical repair in the aspirin only group (1%); no vascular complications occurred in the ticlopidine-aspirin group (P=.1). No bleeding complications occurred in either group. There was no difference in side effects between the two groups (P=.2). There were no medication side effects requiring termination of aspirin. The incidence of side effects requiring termination of ticlopidine was 2.4%. The reason for stopping ticlopidine was skin rash in two patients (1.6%), which resolved after the ticlopidine was discontinued, and leukopenia (neutropenia) in one patient (0.8%). The leukopenia was significant, with an absolute white cell count of <500 cells/mm3, and was complicated by sepsis requiring hospitalization and treatment with broad-spectrum intravenous antibiotics for 2 weeks.
Angiographic and Intravascular Ultrasound
Analysis
Angiographic data were obtained for all lesions (Table
5). The quantitative baseline angiographic measurements
illustrate that the two antiplatelet therapy groups were well
matched according to vessel size and lesion length. The final
angiographic data also were similar in the two groups. The cumulative
distributions of the baseline and final minimum lumen diameters and
percent diameter stenoses in the two groups are shown in Figs 1
and 2, respectively.
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Final quantitative intravascular
ultrasound measurements were performed
for all lesions (Table 6). The final CSA, percent plaque
area, diameter measurements, and eccentricity index were not
significantly different in the two groups. Fig 3 shows
the cumulative distribution of the final stent lumen CSAs of the two
groups. At the proximal reference vessel site, the vessel CSA was
significantly larger in the aspirin group (16.2±5.1 mm2)
than in the ticlopidine-aspirin group (14.9±4.3
mm2, P=.04). The lumen, vessel, and
percent plaque area measurements at the distal and proximal reference
vessel sites were otherwise similar in the two groups.
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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The results of this randomized study evaluating the efficacy and safety of two different antiplatelet therapies administered without anticoagulation after successful intravascular ultrasound–guided stent implantation provide further support for the concept that anticoagulation can be safely withheld when adequate stent expansion is achieved and flow is optimized in the stented and adjacent inflow and outflow segments. The incidence of stent thrombosis for the combined 226 patient cohort was 1.8%, a reflection of the relatively infrequent occurrence of this early angiographic complication after optimized stent implantation. We found no difference in stent thrombosis rates between the two groups. It is worth noting that the incidence of stent thrombosis was 2.1% higher in the aspirin only group. Given the infrequent occurrence of stent thrombosis, it could be argued that the study was not sufficiently large to detect a statistically significant difference in the incidence of stent thrombosis between the two groups.
Although the side effect profile between the two groups was similar, significant leukopenia caused by ticlopidine therapy was documented in one patient (0.8%) who required prolonged hospitalization and treatment of a life-threatening infection with intravenous antibiotics. The principal significant side effect of ticlopidine is idiopathic bone marrow suppression, which manifests as leukopenia in up to 2.0% to 2.5% of patients treated with ticlopidine.29 30 Recovery from the leukopenia typically occurs within 4 to 21 days after the medication is stopped.29 30 The incidence of severe leukopenia with absolute neutrophil counts <500 cells/mm3 is 0.8%.29 30 Although the incidence of leukopenia appears diminished with the short duration of therapy necessary after successful stent implantation, the results of the present study and from previous experience without anticoagulation illustrate that the risk is not abolished and should be considered in the risk and benefit assessment.12
Arterial Thrombus Formation and the Mechanisms of
Action of Ticlopidine and Aspirin
Coronary artery thrombosis remains a
platelet-dependent event even after a metallic stent is
implanted. The stimulus for platelet activation and aggregation is
derived from vascular injury or damage to the vessel wall as occurs
during a coronary intervention; an impairment in the normal
rheology of blood flow (such as in the presence of an underexpanded
stent); and activation of the coagulation factors that culminates in
the formation of thrombin, a strong agonist for platelet
activation.31 32 33 Platelet activation
initiates several
metabolic pathways that result in degranulation of the
platelets and release of additional agonists for platelet
activation and recruitment.34 Platelet degranulation
is mediated by the action of platelet agonists such as ADP,
thromboxane A2, thrombin, and collagen
acting through various receptors and secondary
messengers.35 The final common pathway leading to
platelet aggregation and the formation of a platelet plug or
thrombus is induced by the conformational change and externalization of
the glycoprotein IIb/IIIa receptor.36 The
glycoprotein IIb/IIIa molecule serves as a binding site for
adhesive macromolecules such as fibrinogen and von Willebrand
factor that cross-link adjacent platelets together to form the
platelet plug or the occlusive thrombus.36
Aspirin exerts its effect on reducing thrombotic events in this complex milieu by blocking the formation of thromboxane A2, a powerful mediator of platelet degranulation, through permanent inactivation of the cyclooxygenase enzyme. Ticlopidine has effects on platelet activity that give it a theoretical advantage over aspirin. The primary action of ticlopidine is to irreversibly block the binding of fibrinogen to platelets, an effect that appears to be 85% effective against inhibiting platelet aggregation, the final common pathway to the formation of thrombus.37 38 This effect is not associated with a conformational change in the glycoprotein IIa/IIIb receptor or an alteration of the platelet membrane with the specific mechanism not yet elucidated.39 There have been no reports on whether the combination of aspirin and ticlopidine provides a synergistic effect on reducing platelet activation and aggregation. The potential for such a synergistic effect is appealing, given the difference in their principal mechanism of action and the incomplete effects of both agents in preventing platelet aggregation and thrombus formation.
The present study represents the only randomized comparison of efficacy and safety between the two poststent antiplatelet regimens, with results suggesting that there may be only small differences, if any, in efficacy between treatment with aspirin only and with ticlopidine-aspirin. Despite the lack of comparative information on antiplatelet therapy after successful stent implantation, numerous reports seem to confirm the efficacy of ticlopidine-based therapies after successful optimized stent expansion.11 12 13 14 15 16 17 18 19 20 21 22 Morice et al15 reported on the French multicenter trial on coronary stenting without warfarin (phases II and III) with 1-month treatment with ticlopidine 500 mg/d and aspirin 100 mg/d, and after 2 to 4 weeks of treatment with low-molecular-weight heparin, they reported a 0.9% to 1.5% incidence of stent thrombosis with a 3.6% to 3.8% incidence of vascular or bleeding complications in 498 patients.15 Other investigations report stent thrombosis rates of 0.9% to 3.6% in cohorts of patients treated only with ticlopidine and aspirin in conjunction with low-molecular-weight heparin after a successful stent procedure.16 17 18 19 20 Morice et al22 subsequently reported on the French Registry on coronary stenting without warfarin or intravascular ultrasound guidance (phase V) with only ticlopidine and aspirin in 1156 patients and noted a 1.6% incidence of stent thrombosis and a bleeding or vascular complication rate of 0.6%. In an experience that involved treatment with only ticlopidine 500 mg/d started 3 days before stent implantation, Barragan et al21 noted a 1.1% incidence of stent thrombosis and a 1% incidence of bleeding or vascular complications.
Changing Gold Standards
The primary benefits of treatment
with only antiplatelet
therapy and without anticoagulation after stent implantation are a
reduction in vascular complications and the potential to reduce the
duration of hospitalization, both of which improve the economics of
stent implantation. Even when the slightly increased risk profile of
ticlopidine compared with aspirin is considered, ticlopidine therapy
seems more acceptable than treatment with warfarin, which has never
been documented to reduce thrombosis rates after stent implantation
compared with aspirin or any other antiplatelet agent.
Treatment with ticlopidine, however, does require laboratory monitoring
because of the unpredictable and potentially life-threatening
occurrence of idiopathic bone marrow suppression. Incumbent in any
poststenting antiplatelet or medical regimen is the imperative
need to have acceptable stent thrombosis rates of <1%. In the
present study, that goal was achieved in the
ticlopidine-aspirin group but not in the aspirin only group.
Preliminary experience with a stent that has covalently bound heparin
suggests that heparin coating on a stent may provide an additional
security in consistently reducing stent thrombosis to
<1%.40
Study Limitations
This study has several limitations.
Although the study was
randomized, the randomization was open label. A single- or
double-blind randomization protocol may have provided a more
scientific assessment of the efficacy and safety of the two
antiplatelet regimens. There was a slight imbalance in the
number of patients in each group owing to premature termination of the
study before the expected target of 450 patients after the three deaths
in the aspirin group. With the low incidence of stent thrombosis in the
present era of stent implantation and the relatively small
differences in stent thrombosis rates in the two groups, a larger
cohort of patients clearly is necessary to assess for a significant
difference between the antiplatelet regimens. In view of the
important clinical and regulatory ramifications, such a study would
best be performed as a multicenter trial with angiographic core
laboratory. The stent implantation procedures in this study were
performed with intravascular ultrasound guidance. It cannot be
determined from the present study whether the ultrasound guidance
had an equilibrating effect that minimized the differences in efficacy
in the two antiplatelet regimens. Results of the French
registry suggest that intravascular ultrasound may not be necessary in
most patients. Additional randomized clinical trials may be necessary
to clearly demonstrate the benefit of ultrasound as a component of the
stent procedure. This issue is particularly important when the risk of
stent thrombosis is high, as evident in stent implantation performed
for emergency reasons or in patients with small vessels or long
lesions.
Conclusions
The results of the present study provide further
evidence of
the safety of treatment with only antiplatelet therapy after
optimal stent expansion. Although the difference was not significant,
poststent implantation treatment with ticlopidine and short-term
aspirin was associated with a slightly lower absolute stent thrombosis
rate than treatment with aspirin alone. Until further evidence from
larger studies is provided, no definitive recommendations can be made
regarding the superiority of ticlopidine and short-term aspirin
compared with aspirin therapy alone in the prevention of stent
thrombosis.
Received July 31, 1995; revision received September 27, 1995; accepted October 10, 1995.
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References |
|---|
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TopAbstractIntroductionMethods Results Discussion References |
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1. Roubin GS, Cannon AD, Agrawal SK, Macander PJ, Dean LS, Baxley WA, Breland J. Intracoronary stenting for acute or threatened closure complicating percutaneous transluminal coronary angioplasty. Circulation. 1992;85:916-927.
2. George BS, Voorhees WD, Roubin GS, Fearnot NE, Pinkerton CA, Raizner AE, King SB, Holmes DR, Topol ER, Kereiakes DJ, Hartzler GO. Multicenter investigation of coronary stenting to treat acute or threatened closure after percutaneous transluminal coronary angioplasty: clinical and angiographic outcomes. J Am Coll Cardiol. 1993;22:135-143. [Abstract]
3.
Fischman DL, Leon MB, Baim D, Schatz RA, Penn I, Detre
K, Savage MP, Veltri L, Ricci D, Nobuyoshi M, Cleman M, Heuser R,
Almond D, Teirstein P, Fish D, Colombo A, Brinker J, Moses J, Hirshfeld
J, Bailey S, Ellis S, Rake R, Goldberg S. A randomized
comparison of coronary stent placement and balloon angioplasty
in the treatment of coronary artery disease.
N Engl J Med. 1994;331:496-501.
4.
Serruys PW, de Jaegere P, Kiemeneij F, Macaya C,
Rutsch W, Heyndrickx G, Emanuelsson H, Marco J, Legrand V, Materne P,
Belardi J, Sigwart U, Colombo A, Goy J-J, van den Huevel P, Delcan J,
Morel MA, for the BENESTENT Study Group. A comparison of balloon
expandable stent implantation with balloon angioplasty in patients with
coronary artery disease. N Engl J Med. 1994;331:489-495.
5.
Herrman NC, Buchbinder M, Clemen MW, Fischman D,
Goldberg S, Leon M, Schatz RA, Tierstein P, Walker CM, Hirshfield
JW. Emergent use of balloon expandable coronary artery
stenting for failed percutaneous transluminal
coronary angioplasty. Circulation. 1992;86:812-819.
6. Nath FC, Muller DWM, Ellis SG, Rosenschein U, Chapekis A, Quain L, Zimmerman C, Topol EJ. Thrombosis of a flexible coil coronary stent: frequency, predictors, and clinical outcomes. J Am Coll Cardiol. 1993;21:622-627. [Abstract]
7. Kimura T, Nosaka H, Yokoi H, Iwabuchi M, Nobuyoshi M. Serial angiographic follow-up after Palmaz-Schatz stent implantation: comparison with conventional balloon angioplasty. J Am Coll Cardiol. 1993;21:1557-1563. [Abstract]
8. Carrozza JP, Kuntz RE, Levine MJ, Pomerantz RM, Fishman RF, Mansour M, Gibson CM, Senerchia CC, Diver DJ, Safian RD, Baim DS. Angiographic and clinical outcome of intracoronary stenting: immediate and long-term results from a large single center experience. J Am Coll Cardiol. 1992;20:328-337. [Abstract]
9.
Nakamura S, Colombo A, Gaglione S, Almagor Y, Goldberg
SL, Maiello L, Finci L, Tobis JM. Intracoronary
ultrasound observations during stent implantation.
Circulation. 1994;89:2026-2034.
10. Goldberg SL, Colombo A, Nakamura S, Almagor M, Maiello L, Tobis JM. The benefit of intracoronary ultrasound in the deployment of Palmaz-Schatz stents. J Am Coll Cardiol. 1994;24:996-1003. [Abstract]
11. Hall P, Colombo A, Almagor Y, Maiello L, Nakamura S, Martini G, Tobis JM. Preliminary experience with intravascular ultrasound guided Palmaz-Schatz stenting: the acute and short term results on a consecutive series of patients. J Intervent Cardiol. 1994;7:141-159. [Medline] [Order article via Infotrieve]
12.
Colombo A, Hall P, Nakamura S, Almagor Y, Maiello L,
Martini G, Gaglione A, Goldberg SL, Tobis JM.
Intracoronary stenting without anticoagulation accomplished
with intravascular ultrasound guidance.
Circulation. 1995;91:1676-1688.
13. Russo RJ, Schatz RA, Sklar MA, Johnson AD, Tobis JM, Teirstein PS. Ultrasound guided coronary stent placement without prolonged systemic anticoagulation. J Am Coll Cardiol. 1995;25:50A. Abstract.
14. Blasini R, Mudra H, Schulen H, Regar E, Klauss V, Zitzman E, Paloncy R, Neller P, Neumann FJ, Richardt G, Schmitt C, Schomig A. Intravascular ultrasound guided optimized emergency coronary Palmaz-Schatz stent placement without post procedural systemic anticoagulation. J Am Coll Cardiol. 1995;25:197A. Abstract.
15. Morice MC, Bourdonnec C, Biron Y, Fajadet J, Glatt B, Royer T, Descaves C, Gaspard P, Lienhard Y, Marco J. Coronary stenting without Coumadin: phase III. J Am Coll Cardiol. 1994;23:335A. Abstract.
16. Barragan PT, Silvestri MA, Sainsous JB, Bouvier JL, Comet BL, Simeoni JB. Coronary stenting without anticoagulation. J Am Coll Cardiol. 1994;23:336A.
17. Elias J, Monassier JP, Puel J, Grollier G, Khalife K, Hanssen M, Labbe T, Boulenc JM, Laval G. Medronic Wiktor stent implantation without Coumadin: hospital outcome. Circulation. 1994;90(suppl I):I-124. Abstract.
18. Aubry P, Royer T, Spaulding C, Lancelin B, Faivre R, Henry M, Livarek B, Rioux P, Valette B, Masquet C, Morice MC, Zemour G. A lower rate of complications after Gianturco-Roubin coronary stenting using a new antiplatelet and anticoagulant protocol. Circulation. 1994;90(suppl I):I-124. Abstract.
19. Carvalho H, Fajadet J, Jordan C, Cassagneau B, Robert G, Marco J. Reduction of subacute stent thrombosis rate after coronary stenting using a new anticoagulant protocol. Circulation. 1994;90(suppl I):I-125. Abstract.
20. Jordan C, Carvalho H, Fajadet J, Cassagneau B, Robert G, Marco J. Reduction of subacute stent thrombosis rate after coronary stenting using a new anticoagulant protocol. Circulation. 1994;90(suppl I):I-125.
21. Barragan P, Silvestri M, Sainsous J, Simeoni JB, Bayet G, Bouvier JL, Comet B. Prevention of subacute occlusion after coronary stenting with ticlopidine regimen without intravascular ultrasound guided stenting. J Am Coll Cardiol. 1995;25:182A. Abstract.
22. Morice MC, Breton C, Bunouf P, Cattan S, Eltchaninoff H, Henry M, Joly P, Livarek B, Pillere R, Rioux P, Spaulding C, Zemour G. Coronary stenting without anticoagulant, without intravascular ultrasound results of the French registry. Circulation. 1995;92:I-796. Abstract.
23. Colombo A, Hall P, Thomas J, Almagor Y, Finci L. Initial experience with the disarticulated (one-half) Palmaz-Schatz stent: a technical report. Cathet Cardiovasc Diagn. 1992;25:304-308. [Medline] [Order article via Infotrieve]
24.
Nakamura S, Hall P, Blengino S, Maiello L, Itoh A,
Finci L, Colombo A. Reproducibility of intravascular ultrasound
measurements. Eur Heart J. 1995;16:201. Abstract.
25. Scoblianko DP, Brown G, Mitten S. A new digital electronic caliper for measurement of coronary arterial stenosis: a comparison with visual and computer assisted measurements. Am J Cardiol. 1984;53:689-693. [Medline] [Order article via Infotrieve]
26. Theron HT, Lambert CR, Pepine CJ. Video densitometry versus digital calipers for quantitative coronary angiography. Am J Cardiol. 1990;66:1886-1890.
27.
Ryan TJ, Faxon DP, Gunnar RM, Kennedy JW, King SB 3rd,
Loop FD, Peterson KL, Reeves TJ, Williams DO, Winters WL Jr. Guidelines
for percutaneous transluminal coronary
angioplasty: a report of the American College of
Cardiology/American Heart Association Task Force on
assessment of diagnostic and therapeutic
cardiovascular procedures.
Circulation. 1988;78:486-502.
28. The TIMI Study Group. The thrombolysis in acute myocardial infarction trial. N Engl J Med. 1985;312:932-936. [Medline] [Order article via Infotrieve]
29. Hass WK, Easton JD, Adams HP Jr, Pryse-Phillips W, Molony BA, Anderson S, Kamm B, for the Ticlopidine Aspirin Stroke Study Group. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high risk patients. N Engl J Med. 1989;321:501-507. [Abstract]
30. Piscotta V. Drug induced agranulocytosis. Drugs. 1978;15:132-143.[Medline] [Order article via Infotrieve]
31. Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathophysiology of coronary artery disease and the acute coronary syndromes. N Engl J Med. 1992;326:242-250, 310-318. [Medline] [Order article via Infotrieve]
32.
Lefkovits J, Plow EF, Topol EJ. Platelet
glycoprotein IIb/IIIa receptors in
cardiovascular medicine. N Engl
J Med. 1995;332:1553-1559.
33. Couglin SR, Vu THH, Hung DR, Wheaton VI. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. J Clin Invest. 1992;89:351-355.
34. Coller BS. Platelets in cardiovascular thrombosis and thrombolysis. In: Fozard HA, Haber E, Jennings RB, Katz AM, Morgan HE, eds. The Heart and Cardiovascular System: Scientific Foundations. 2nd ed. New York, NY: Raven Press; 1991;1:219-273.
35. Berridge MJ. Inositol triphosphate and diacylglycerol: two interacting second messengers. Annu Rev Biochem. 1987;56:159-193. [Medline] [Order article via Infotrieve]
36. Coller BS, Peerschke EI, Scudder LE, Sullivan CA. A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets produces a thromasthenic-like state in normal platelets and binds to gycoprotein IIb and or IIIa. J Clin Invest. 1983;72:325-338.
37. Bernat A, Vallee E, Maffrand JP, Gordan JL. The role of platelets and ADP in experimental thrombosis induced by venous stasis in the rat. Thromb Res. 1988;52:65-70. [Medline] [Order article via Infotrieve]
38. Maffrand JP, Defreyn G, Bernat A, Delebassee D, Tissinier AM. Reviewed pharmacology of ticlopidine. Angiologie Suppl. 1988;77:6-13.
39. Hardisty RM, Powling MJ, Nokes TJC. The action of ticlopidine on human platelets: studies on aggregation, secretion, calcium mobilization, and membrane glycoproteins. Thromb Haemost. 1990;64:105-115.
40. Serruys PW, Emanuelsson H, Macaya C, Rutsch W, Heydrickx G, Suryapranata H, Legrand V, Guy J-J, Materne P, Bonnier H. BNESTENT-II Pilot Study: in-hospital results of phase 1, 2, 3, 4. Eur Heart J. 1995;290:16.
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 |
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|
|
|
|
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|
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|
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|
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|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 A. Oshima, D. Itchhaporia, and P. Fitzgerald New developments in intravascular ultrasound Vascular Medicine, November 1, 1998; 3(4): 281 - 290. [Abstract] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
A L Calver, K D Dawkins, H H Gray, G A Haywood, J M Morgan, and I A Simpson Intracoronary Multi-link stents: experience in 218 patients using aspirin alone Heart, November 1, 1998; 80(5): 499 - 504. [Abstract] [Full Text]
|
|
|
|
|
|
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|
|
|
|
|
|
M. E. Bertrand, V. Legrand, J. Boland, E. Fleck, J. Bonnier, H. Emmanuelson, M. Vrolix, L. Missault, S. Chierchia, M. Casaccia, et al. Randomized Multicenter Comparison of Conventional Anticoagulation Versus Antiplatelet Therapy in Unplanned and Elective Coronary Stenting : The Full Anticoagulation Versus Aspirin and Ticlopidine (FANTASTIC) Study Circulation, October 20, 1998; 98(16): 1597 - 1603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y Yoshitomi, S Kojima, T Sugi, M Yano, Y Matsumoto, and M Kuramochi Antiplatelet treatment with cilostazol after stent implantation Heart, October 1, 1998; 80(4): 393 - 396. [Abstract] [Full Text]
|
|
|
|
 |
|
 J.-P. Bossavy, C. Thalamas, L. Sagnard, A. Barret, K. Sakariassen, B. Boneu, and Y. Cadroy A Double-Blind Randomized Comparison of Combined Aspirin and Ticlopidine Therapy Versus Aspirin or Ticlopidine Alone on Experimental Arterial Thrombogenesis in Humans Blood, September 1, 1998; 92(5): 1518 - 1525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Schiele, N. Meneveau, A. Vuillemenot, D. D. Zhang, S. Gupta, M. Mercier, N. Danchin, B. Bertrand, J.-P. Bassand, and on behalf of the RESIST Study Group Impact of intravascular ultrasound guidance in stent deployment on 6-month restenosis rate: a multicenter, randomized study comparing two strategies--with and without intravascular ultrasound guidance J. Am. Coll. Cardiol., August 1, 1998; 32(2): 320 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
D. J. Kereiakes, A. M. Lincoff, D. P. Miller, J. E. Tcheng, C. F. Cabot, K. M. Anderson, H. F. Weisman, R. M. Califf, and E. J. Topol Abciximab Therapy and Unplanned Coronary Stent Deployment : Favorable Effects on Stent Use, Clinical Outcomes, and Bleeding Complications Circulation, March 10, 1998; 97(9): 857 - 864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C di Mario, B Reimers, Y Almagor, I Moussa, L Di Francesco, M Ferraro, M B Leon, K Richter, and A Colombo Procedural and follow up results with a new balloon expandable stent in unselected lesions Heart, March 1, 1998; 79(3): 234 - 241. [Abstract] [Full Text]
|
|
|
|
|
|
R. Altman Controversies in Antithrombotic Therapy in Cardiovascular Diseases Clinical and Applied Thrombosis/Hemostasis, January 1, 1998; 4(1): 11 - 24. [Abstract] [PDF]
|
|
|
|
|
|
T. P. Lecompte, C. Lecrubier, C. Bouloux, M.-H. Horellou, J. Galleyrand, J.-P. Maffrand, and M. M. Samama Antiplatelet Effects of the Addition of Acetylsalicylic Acid 40 Mg Daily to Ticlopidine in Human Healthy Volunteers Clinical and Applied Thrombosis/Hemostasis, October 1, 1997; 3(4): 245 - 250. [Abstract] [PDF]
|
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|
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|
D. J. Kereiakes, N. Kleiman, J. J. Ferguson, J. P. Runyon, T. M. Broderick, N. A. Higby, L. H. Martin, G. Hantsbarger, S. McDonald, and R. J. Anders Sustained Platelet Glycoprotein IIb/IIIa Blockade With Oral Xemilofiban in 170 Patients After Coronary Stent Deployment Circulation, August 19, 1997; 96(4): 1117 - 1121. [Abstract] [Full Text]
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D. S. Baim and J. P. Carrozza Jr Stent Thrombosis: Closing in on the Best Preventive Treatment Circulation, March 4, 1997; 95(5): 1098 - 1100. [Full Text]
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R. Albiero, P. Hall, A. Itoh, S. Blengino, S. Nakamura, G. Martini, M. Ferraro, and A. Colombo Results of a Consecutive Series of Patients Receiving Only Antiplatelet Therapy After Optimized Stent Implantation: Comparison of Aspirin Alone Versus Combined Ticlopidine and Aspirin Therapy Circulation, March 4, 1997; 95(5): 1145 - 1156. [Abstract] [Full Text]
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 N. G Uren and N. A. Chronos Intracoronary stents BMJ, October 12, 1996; 313(7062): 892 - 893. [Full Text]
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 Ticlopidine, Aspirin, and Stents Journal Watch Cardiology, April 1, 1996; 1996(401): 5 - 5. [Full Text]
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