throbber
JACC Vol. 29, No. 1
`January 1997;21–7
`
`21
`
`High Pressure Assisted Coronary Stent Implantation
`Accomplished Without Intravascular Ultrasound Guidance and
`Subsequent Anticoagulation
`
`SHIGERU NAKAMURA, MD, PATRICK HALL, MD, FACC,* ANTONIO GAGLIONE, MD,†
`FABIO TIECCO, MD,† MARINELLA DI MAGGIO, MD,† LUIGI MAIELLO, MD,*
`GIOVANNI MARTINI, CCP,* ANTONIO COLOMBO, MD, FACC*
`Ohta, Japan and Milan and Bari, Italy
`
`Objectives. The purpose of this study was to determine the
`efficacy of treatment with antiplatelet therapy and no anticoagu-
`lation after high pressure assisted coronary stent implantation
`performed without intravascular ultrasound (IVUS) guidance.
`Background. Previous studies have shown that during IVUS-
`guided Palmaz-Schatz coronary stenting, it is safe to withhold
`anticoagulation when stent expansion has been optimized by high
`pressure balloon dilation.
`Methods. Patients that had successful coronary stenting with-
`out IVUS guidance were treated with ticlopidine, 500 mg/day, and
`aspirin, 325 mg/day, for 1 month and then received only aspirin,
`325 mg/day, indefinitely. Patients were not treated with warfarin
`(Coumadin) or heparin after successful stenting. Clinical and
`angiographic events were assessed at 1 month.
`Results. A total of 201 intracoronary stents were implanted in
`127 patients with 137 lesions. The average number of stents per
`
`lesion was 1.4 ⴞ 0.8, and the average number of stents per patient
`was 1.6 ⴞ 1.1. Stent deployment was performed for elective
`indications in 79% of procedures and for emergency indications in
`21%. There were four stent thrombosis events for a per patient
`event rate of 3.1% and a per lesion event rate of 2.9%.
`Conclusions. After high pressure assisted stenting performed
`without IVUS guidance, there was an acceptable incidence of 3.1%
`of stent thrombosis with the combination of short-term ticlopidine
`and aspirin therapy and no anticoagulation. Although the study
`involved only 127 patients, the results support the relative safety
`of stenting without IVUS guidance and with antiplatelet therapy
`only in comparison to historical trials on stenting performed with
`postprocedure anticoagulation.
`
`(J Am Coll Cardiol 1977;29:21–7)
`䉷1997 by the American College of Cardiology
`
`Coronary stent implantation has been shown to reduce the
`morbidity of acute or threatened vessel closure after coronary
`angioplasty (1,2). The Belgian Netherlands Stent study
`(BENESTENT) and Stent and Restenosis Study (STRESS)
`randomized trials comparing stents to angioplasty in the
`treatment of de novo coronary lesions demonstrated a signif-
`icant reduction in the angiographic restenosis and late isch-
`emia driven clinical events in the group treated with stents
`(3,4). The BENESTENT trial also demonstrated a reduction in
`major clinical events after coronary stent implantation in
`comparison with coronary angioplasty (3). These contributed
`to a marked increase in the use of intracoronary stents for the
`treatment of symptomatic coronary artery disease. The utility
`of stent implantation, however, continues to be limited by a
`
`From the Ohta General Hospital, Division of Cardiology, Ohta, Japan;
`*Centro Cuore Columbus, Milan, Italy; and †Villa Bianca Hospital, University of
`Bari School of Medicine, Bari, Italy. This work was presented at the 67th Annual
`Scientific Sessions of the American Heart Association, Dallas, Texas, November
`1994.
`Manuscript received July 13, 1995; revised manuscript received July 11, 1996,
`accepted September 16, 1996.
`Address for correspondence: Dr. Antonio Colombo, Centro Cuore Colum-
`bus, Via M. Buonarotti, 48, 20145 Milan, Italy.
`
`in-
`stringent postprocedure anticoagulation regimen that
`creases vascular and bleeding complications without providing
`sufficient protection against stent thrombosis (5–8).
`A cause of stent thrombosis was proposed to be stent
`underexpansion after a study of
`intravascular ultrasound
`(IVUS) evaluation after stent deployment demonstrated that
`80% of stents were underexpanded when the final result was
`judged only with angiographic assessment (9,10). In a subse-
`quent prospective study on IVUS-guided coronary stent im-
`plantation in which stent expansion was optimized with the use
`of high pressure balloon dilations, there was a 1.1% stent
`thrombosis rate in 321 patients treated only with antiplatelet
`therapy after a successful procedure (11,12).
`The strategy of stent implantation with IVUS guidance and
`elimination of postprocedure anticoagulation therapy also
`resulted in a reduction in hospital stay (12). However, this
`strategy adds to the expense and increases procedure time of
`the stent implantation procedure. Thus, the purpose of the
`present study was to evaluate the safety and efficacy of
`treatment with combination ticlopidine and aspirin after a
`successful stent implantation procedure guided by an angio-
`graphic assessment only, without IVUS evaluation.
`
`䉷1997 by the American College of Cardiology
`Published by Elsevier Science Inc.
`
`0735-1097/97/$17.00
`PII S0735-1097(96)00431-7
`
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`

`

`22
`
`NAKAMURA ET AL.
`HIGH PRESSURE STENTING WITHOUT INTRAVASCULAR ULTRASOUND
`
`JACC Vol. 29, No. 1
`January 1997;21–7
`
`Abbreviations and Acronyms
`⫽ activated clotting time
`ACT
`BENESTENT ⫽ Belgian Netherlands Stent study
`⫽ electrocardiographic, electrocardiogram
`ECG
`⫽ intravascular ultrasound
`IVUS
`⫽ Stent Restenosis Study
`STRESS
`⫽ Thrombolysis in Myocardial Infarction
`TIMI
`
`Methods
`From October 26, 1993 to October 25, 1994, 132 patients
`underwent successful high pressure assisted intracoronary
`stent implantation without IVUS guidance. A total of 127
`patients (91 consecutive patients in Villa Bianca Hospital,
`Bari, Italy, and 36 selected patients in Columbus Clinic, Milan,
`Italy) had a successful coronary stent implantation and did not
`receive anticoagulation after the stent procedure. The patients
`from the Columbus Clinic were not a consecutive series of
`patients because of the general policy of performing stent
`implantation with IVUS guidance. These patients, however,
`were not specifically or exclusively low risk patients. In this last
`group of patients IVUS was not performed because of severe
`proximal tortuosity in 12 patients (33%) or because of signif-
`icant angulation (⬎45⬚) at the lesion site after placement of a
`stent with a coil design (Gianturco-Roubin, Wiktor, Cordis
`stents) in 10 patients (28%).
`In these patients the indication for stent implantation was
`emergent (acute or threatened closure) in eight lesions (22%)
`and nonemergent (chronic occlusions) in five lesions (14%).
`These indications are comparable to the ones reported for the
`entire group.
`The entry criteria for the study were evidence of coronary
`artery disease manifested by clinical symptoms or objective
`evidence of myocardial ischemia or exercise testing, nuclear
`scintigraphy or pharmacologic stress echocardiogram, and
`angiographic evidence of single- or multiple-vessel disease with
`a target lesion stenosis of ⬎70% by visual assessment. Specific
`exclusion criteria included 1) small vessels ⬍2.5 mm by visual
`estimate; 2) angiographically diffuse distal disease that might
`compromise outflow after stent insertion; 3) patients who were
`taking Coumadin before the stent procedure and who required
`anticoagulation with Coumadin for other medical reasons; and
`4) suboptimal angiographic results due to residual dissection
`or suboptimal expansion at the end of the stent procedure that
`was thought to require continued short-term anticoagulation
`therapy with Coumadin for 1 month. During the course of this
`investigation five patients had successful stent implantation
`without IVUS guidance and received Coumadin therapy after
`the stent procedure for poor distal run off (n ⫽ 2), compro-
`mised side branch (n ⫽ 2) or residual dissection (n ⫽ 1). There
`were no complications of stent thrombosis in these five pa-
`tients.
`Stent implantation procedure. Patients received aspirin,
`325 mg, and calcium antagonists before the stent procedure.
`
`All coronary tent implantation procedures were performed
`from the standard femoral artery approach using an 8F or 9F
`guiding catheter. A bolus of 10,000 U of heparin was admin-
`istered after insertion of the femoral sheath. A repeat bolus of
`5,000 U of heparin was given to maintain an activated clotting
`time (ACT) ⬎250 s or if the procedure was longer than 3 h.
`Patients did not receive dextran or dipyridamole (Persantine)
`before, during or after the stent procedure. After appropriate
`baseline angiograms were obtained,
`lesion predilation was
`performed. There were five different types of stents deployed
`during this study: the Palmaz-Schatz stent (Johnson and John-
`son Interventional Systems Co.), the Gianturco-Roubin stent
`(Cook Cardiology), the Wiktor stent (Medtronic), the Micro
`stent (Applied Vascular Engineering) and the Cordis stent
`(Cordis Corp.). Palmaz-Schatz stents were hand-crimped on
`balloons and delivered bare as previously described (12).
`There was no balloon size selection protocol for the stent
`optimization. Each operator selected an appropriate balloon
`size based on his or her visual assessment of the angiographic
`reference diameter. Typically, noncompliant balloons (NC
`Shadow, SCIMED Life Systems, or High Energy, Mansfield)
`were used for final high pressure dilations.
`The indications for stent deployment were defined as
`follows. Acute occlusion stent implantation was performed to
`relieve ischemia associated with complete vessel closure
`(100%) after angioplasty with Thrombolysis in Myocardial
`Infarction (TIMI) flow grade 0 or 1. Threatened closure stent
`implantation was performed when the angioplasty was compli-
`cated by a longitudinal or spiral dissection associated with
`⬎50% lumen encroachment (with or without compromised
`flow) and symptomatic or electrocardiographic (ECG) evi-
`dence of ischemia. Suboptimal result stent placement was
`defined as insertion of a stent for a focal dissection or sig-
`nificant vascular recoil after angioplasty that resulted in ⬎50%
`lumen narrowing not associated with ischemia. Restenosis stent
`implantation was performed for lesions with a history of
`restenosis after one or more previous angioplasty procedures.
`Chronic occlusion stent insertion was performed after reopen-
`ing a vessel that had been occluded for longer than 2 months.
`Elective stenting was performed as the intention to stent de
`novo lesions before the procedure. Emergency stent implanta-
`tion was considered stent implantation performed for acute or
`threatened closure and acute myocardial infarction.
`Postprocedure medication protocol. A decision to treat
`with only antiplatelet therapy at the completion of the stent
`procedure required angiographic success, defined as the
`achievement of ⬍20% residual stenosis and no evidence of
`untreated residual dissection by visual assessment at the time
`of the stent implantation procedure. After a successful stent
`implantation procedure, no further heparin was infused. Fem-
`oral sheaths were removed when the ACT dropped below
`150 s. When a stent procedure was completed in the evening,
`intravenous heparin was infused until the following morning
`before being discontinued with subsequent sheath removal.
`Ticlopidine was not administered before or during the stent
`procedure but was initiated after a successful procedure.
`
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`

`

`JACC Vol. 29, No. 1
`January 1997;21–7
`
`NAKAMURA ET AL.
`HIGH PRESSURE STENTING WITHOUT INTRAVASCULAR ULTRASOUND
`
`23
`
`Antiplatelet therapy with ticlopidine, 500 mg in two equal
`doses per day, and aspirin, 325 mg/day, was initiated after a
`successful stent procedure and continued for 1 month. After 1
`month, ticlopidine was discontinued and patients were treated
`with aspirin, 325 mg/day, indefinitely.
`Quantitative angiographic measurements. Quantitative
`coronary angiographic analysis was performed using digital
`calipers by experienced angiographers not involved in the stent
`procedure. Angiographic measurements were obtained during
`diastole. The lesions were measured from an optically magni-
`fied image in a single, matched “worst” view using digital
`calipers (Brown and Sharp) using the guiding catheter as the
`reference object for magnification calibration. Previous studies
`have shown that digital calipers correlate closely with
`computer-assisted methods with a low interobserver and in-
`traobserver variability (13,14). Measurements of the reference
`vessel diameters, minimal lumen diameter and diameter ste-
`nosis were obtained on the baseline and final angiograms. The
`average of the proximal and distal reference vessel diameters
`was used as the index reference vessel diameter for percent
`diameter stenosis calculations. When the lesions were total
`occlusions or at an ostial location, only one reference vessel
`measurement was possible on the baseline angiogram, and this
`measurement site was used for the index reference diameters.
`Lesion length was measured on the baseline angiogram as the
`distance from the proximal to distal lesion shoulder. Lesions
`were characterized according to the modified American Col-
`lege of Cardiology/American Heart Association (ACC/AHA)
`score (15). Thrombus was defined as a filling defect seen in
`multiple projections surrounded by contrast agent in the
`absence of calcification. TIMI flow grade was recorded at the
`time of the initial procedure to characterize the indication for
`stenting, as previously described (16).
`Study end points and events. The study end points were
`angiographic and clinical events that occurred within the first
`month of a successful stent procedure. The short-term events
`were carefully assessed through regular and uniform telephone
`contact with all patients between 1 and 5 months after the stent
`procedure. Any stent thrombosis occurring within the first
`month of the stent procedure was considered an angiographic
`event. Acute thrombotic events were defined as angiographically
`documented occlusion with TIMI grade flow 0 at the stent site
`occurring within 24 h of the stent procedure. Subacute throm-
`botic events were angiographically documented occlusions with
`TIMI flow grade 0 at the stent site occurring beyond 24 h of the
`stent procedure. Major clinical events were considered death,
`aortocoronary bypass surgery, myocardial infarction (Q wave
`or non–Q wave) and emergency repeat intervention (bail-out
`stenting or repeat angioplasty). Specific major event definitions
`were as follows: death—any death irrespective of cause. A
`diagnosis of myocardial infarction was made when new patho-
`logic Q waves were documented (ⱖ0.14 s) on an ECG in
`conjunction with elevation of creatine kinase to greater than
`twice the upper limit of normal (Q wave myocardial infarction)
`or if there was elevation of the cardiac enzymes to greater than
`twice the upper limit of normal without the development of
`
`Table 1. Clinical Characteristics (n ⫽ 127)
`
`Lesions
`Age (yr)*
`Ejection fraction (%)*
`Male
`Previous myocardial infarction
`Previous PTCA
`Previous CABG
`Multivessel disease
`Unstable angina
`Smoking
`Hypercholesterolemia
`Hypertension
`Family history
`Diabetes
`
`No. (%)
`
`137
`58 ⫾ 10
`53 ⫾ 11
`117 (82)
`40 (62)
`27 (21)
`10 (8)
`58 (45)
`56 (44)
`84 (66)
`66 (52)
`54 (43)
`46 (36)
`21 (17)
`
`*Mean value ⫾ SD. CABG ⫽ coronary artery bypass grafting; PTCA ⫽
`percutaneous transluminal coronary angioplasty.
`
`new pathologic Q waves (non–Q wave myocardial infarction).
`Emergency coronary artery bypass graft surgery involved imme-
`diate transfer of the patient from the catheterization labora-
`tory to the operating room. Nonemergent elective coronary
`bypass surgery was performed more than 24 h after a stent
`procedure had failed in the absence of ischemia or evolving
`myocardial
`infarction. Emergency intervention was bail-out
`stent implantation or emergency angioplasty performed for
`ongoing acute ischemia or evolving myocardial infarction in
`the setting of an angiographically documented stent thrombo-
`sis event.
`Statistics. Continuous variables were expressed as mean
`value ⫾ SD. Angiographic measurements of baseline and
`poststent implantation were compared using the paired two-
`tailed t test. Comparisons between the stent thrombosis and
`nonstent thrombosis groups were performed using the Fisher
`exact probability test and the Mann-Whitney U test. Differ-
`ences were considered statistically significant at p ⬍ 0.05.
`
`Results
`Clinical, angiographic and procedural characteristics. A
`total of 127 patients with 137 stented lesions were treated only
`with antiplatelet therapy after successful high pressure assisted
`coronary stent implantation. Intravascular ultrasound evalua-
`tion was not performed in any of the lesions. Baseline patient
`and angiographic characteristics are shown in Tables 1 and 2.
`Procedural characteristics of stent implantations are pre-
`sented in Table 3. Elective stent placement was performed in
`108 lesions (79%). Emergency stent deployment was done in
`29 lesions (21%). A total of 201 stents were implanted with five
`different types of stents being used. The average number of
`stents per lesion was 1.4 ⫾ 0.8 (range 0.5 to 6.0). The average
`number of stents per patient was 1.6 ⫾ 1.1 (range 0.5 to 6.0).
`The short Palmaz-Schatz stent and 1- or 2-unit Micro Stents
`(each unit is 4 mm) were considered half (0.5) stents for
`calculating the mean number of stents per lesion or patient.
`
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`

`24
`
`NAKAMURA ET AL.
`HIGH PRESSURE STENTING WITHOUT INTRAVASCULAR ULTRASOUND
`
`JACC Vol. 29, No. 1
`January 1997;21–7
`
`Table 2. Baseline Angiographic Characteristics (n ⫽ 137)
`
`Table 4. Quantitative Angiographic Measurements (n ⫽137)
`Baseline
`
`Final
`
`No. (%)
`
`Vessel distribution
`LAD
`RCA
`LCx
`SVG
`LMCA
`Lesion site
`Ostial
`Proximal
`Mid
`Distal
`Lesion type*
`A
`B1
`B2
`C
`Small vessels (⬍3.0 mm)
`Bifurcations
`Long lesions (⬎20 mm)
`Chronic occlusions
`Thrombus
`Bend lesions (⬎45)
`
`75 (55)
`32 (23)
`19 (14)
`9 (7)
`2 (1)
`
`7 (5)
`78 (58)
`46 (33)
`6 (4)
`
`20 (15)
`47 (34)
`39 (28)
`31 (23)
`47 (34)
`24 (18)
`21 (15)
`16 (12)
`11 (8)
`8 (6)
`
`*Modified American Heart Association/American College of Cardiology
`criteria. LCx ⫽ left circumflex coronary artery; LAD ⫽ left anterior descending
`coronary artery; LMCA ⫽ left main coronary artery; RCA ⫽ right coronary
`artery; SVG ⫽ saphenous vein graft.
`
`More than one stent (multiple stents) were implanted in 34
`lesions (25%) and 42 patients (33%).
`Quantitative angiographic measurements and procedural
`data are presented in Table 4. The baseline minimal lumen
`
`Table 3. Stent Implantation Procedure Characteristics (n ⫽ 137)
`No. (%)
`
`Emergency stent implantation
`Threatened closure
`Acute closure
`Acute myocardial infarction
`Nonemergent stent implantation
`Elective
`Suboptimal PTCA
`Chronic occlusion
`Total stents
`Stent type and number
`Palmaz-Schatz (15 mm)
`Short Palmaz-Schatz (7 mm)
`Gianturco-Roubin
`Wiktor
`Micro
`Cordis
`Number of stents/lesion
`1 stent/lesion
`2 stents/lesion
`3 stents or more/lesion
`Average number of stents/lesion*
`Average number of stents/patient*
`
`*Mean value ⫾ SD.
`
`29 (21)
`23 (17)
`5 (4)
`1 (1)
`108 (79)
`89 (65)
`7 (5)
`16 (12)
`201
`
`126 (63)
`24 (12)
`29 (14)
`16 (8)
`4 (2)
`2 (1)
`
`103 (75)
`19 (14)
`15 (11)
`1.4 ⫾ 0.8
`1.6 ⫾ 1.1
`
`Reference vessel (mm)
`Minimal lumen diameter (mm)
`Diameter stenosis (%)
`Lesion length (mm)
`Final balloon size (mm)
`Balloon/artery ratio
`Maximal inflation pressure (atm)
`Residual dissection [no. (%)]†
`
`3.12 ⫾ 0.41
`0.87 ⫾ 0.50
`71 ⫾ 18
`12.22 ⫾ 7.72
`
`3.13 ⫾ 0.40
`2.94 ⫾ 0.89*
`8 ⫾ 15*
`
`3.32 ⫾ 0.38
`1.03 ⫾ 0.14
`17.4 ⫾ 2.4
`6 (4.4%)
`
`*p ⬍ 0.0001 (comparison between baseline and post-stent implantation).
`†Dissection noted at the time of core laboratory angiographic measurements
`were performed. Data are presented as mean value ⫾ SD, unless otherwise
`indicated.
`
`diameter of 0.87 ⫾ 0.50 mm was significantly improved to a
`final stent diameter of 2.94 ⫾ 0.89 mm. The percent diameter
`stenosis was improved from 71 ⫾ 18% to 8 ⫾ 14%. The results
`were achieved using a final balloon size of 3.3 ⫾ 0.4 mm (range
`2.5 to 4.5). The maximal inflation pressure at final balloon
`dilation was 17.4 ⫾ 2.4 atm (range 8 to 20). Pressure ⱕ10 atm
`was used for the final balloon dilation in four lesions (3%). In
`these lesions, final dilations were performed with an oversized
`balloon to further improve the angiographic result, and low
`pressure was used in an attempt to limit the risk of vessel
`rupture. In all of these lesions, high pressure dilations with a
`smaller, appropriately sized balloon by angiographic variables
`preceded the final low pressure inflation. The final balloon/
`artery ratio (proximal reference site) was 1.03 ⫾ 0.14. At the
`time of postprocedure angiographic measurements, residual
`dissection was noted at the stent site in six lesions (4.4%). The
`dissection was proximal to the stent in two lesions (1.5%) and
`distal to the stent in four lesions (2.9%).
`Short-term angiographic and clinical events. The mean
`hospital stay after stent implantation was 2.1 ⫾ 1.8 days.
`Follow-up was obtained in all patients between 1 and 5 months
`after the stent implantation procedure at a mean of 4.9 ⫾ 2.3
`months. There were four stent thrombosis events, giving a per
`lesion stent thrombosis event rate of 2.9% and a per patient
`event rate of 3.1%. Acute stent thrombosis occurred in one
`patient (0.8%) 3 h after the procedure. Subacute stent throm-
`bosis occurred in three patients (2.4%) with one lesion each
`(2.2%) at 3 days (n ⫽ 1) and 5 days (n ⫽ 2) after the stent
`implantation procedure. The stent thrombosis events occurred
`during the hospital stay in three patients (2.4%) and after the
`hospital stay in one patient (0.8%). An emergency intervention
`was performed in all four patients, with additional rescue stent
`implantation being necessary in two of the patients (1.6%).
`One of these patients underwent emergency bypass surgery
`owing to extensive thrombus even after the intervention. One
`patient developed Q wave myocardial infarction and three
`patients had non–Q wave infarction.
`No major clinical event occurred in the other patients
`within the 1-month follow-up period. There was no vascular or
`bleeding complications after the stent implantation procedure.
`Leukopenia was noted in one patient (1%) due to ticlopidine
`
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`

`JACC Vol. 29, No. 1
`January 1997;21–7
`
`NAKAMURA ET AL.
`HIGH PRESSURE STENTING WITHOUT INTRAVASCULAR ULTRASOUND
`
`25
`
`Table 5. Factors Associated With Stent Thrombosis
`
`Factors
`
`Unstable angina
`Prior myocardial infarction
`Emergency indication
`Occlusion on baseline angiogram
`Mean reference vessel (mm)
`Baseline MLD (mm)
`Baseline diameter stenosis (%)
`Final stent MLD (mm)
`Final diameter stenosis (%)
`Lesion length (mm)
`Inflation pressure (atm)
`Balloon/artery ratio
`
`No Stent
`Thrombosis
`(n ⫽ 133)
`
`58 (44)
`78 (59)
`28 (26)
`18 (14)
`3.10 ⫾ 0.40
`0.89 ⫾ 0.49
`70 ⫾ 17
`2.96 ⫾ 0.89
`7 ⫾ 15
`12.2 ⫾ 7.7
`17.4 ⫾ 2.4
`1.04 ⫾ 0.15
`
`Stent
`Thrombosis
`(n ⫽ 4)
`
`2 (50)
`4 (100)
`0 (0)
`2 (50)
`3.55 ⫾ 0.50
`0.28 ⫾ 0.33*
`93 ⫾ 8*
`2.26 ⫾ 0.29*
`34 ⫾ 3*
`12.4 ⫾ 9.3
`18.0 ⫾ 1.3
`0.90 ⫾ 0.06*
`
`*p ⬍ 0.05. Data are presented as mean value ⫾ SD or number (%). MLD ⫽
`Minimal lumen diameter.
`
`within the first month of the stent procedure. This patient was
`observed in the hospital for 5 days and leukopenia resolved
`after discontinuation of ticlopidine.
`Comparison between the stent thrombosis and no stent
`thrombosis groups. The clinical and procedural factors in the
`group with stent thrombosis (4 lesions) and the group with no
`stent thrombosis (133 lesions) were analyzed (Table 5), al-
`though statistical comparison between the two groups suffers
`from the low number of overall patients and the low number of
`stent
`thrombosis events. Stent
`thrombosis occurred more
`frequently in lesions with occlusions at baseline angiography.
`Dilation strategies also played a role in stent thrombosis. Stent
`thrombosis occurred more frequently with a low final balloon/
`artery (proximal reference) ratio and high residual stenosis
`(⬎30%), which may be a reflection of the low final balloon/
`artery ratio. The frequency distribution of the final percent
`diameter stenosis, the balloon/artery ratio and final stent
`minimal lumen diameter and the relation to stent thrombosis
`are shown in Figure 1. There was no difference at the maximal
`inflation pressure between two groups. None of the lesions
`with stent thrombosis had angiographically evident calcifica-
`tion or evidence of residual dissection at the time of the stent
`implantation or at the time the final angiographic measure-
`ments were performed.
`
`Discussion
`Previous IVUS-guided stent implantation studies demon-
`strated the benefit of final high pressure balloon dilations to
`appropriately and safely expand stents and emphasized the
`clinical importance of achieving good stent expansion in pa-
`tients treated only with antiplatelet agents and no postproce-
`dure anticoagulation (10–12). The present study evaluated a
`strategy of high pressure optimization without IVUS guidance
`or postprocedure anticoagulation. In a mixed population of
`127 patients who underwent both elective and emergency stent
`implantation, there was a stent thrombosis event rate of 3.1%
`
`Figure 1. A, Frequency distribution of final percent diameter stenosis.
`B, Frequency distribution of balloon/artery (proximal reference) ratio.
`C, Frequency distribution of final stent minimal lumen diameter.
`
`per patient and there were no vascular or bleeding complica-
`tions due to the absence of postprocedure anticoagulation.
`Comparison with other studies. The stent thrombosis rate
`in the present study was similar to the stent thrombosis rates of
`3.5% for elective stent implantation in both the BENESTENT
`and the STRESS trials, and slightly less than the stent throm-
`bosis rate of 4.7% for both elective and emergency stent
`implantation in the STRESS trial despite treatment without
`
`Downloaded From: http://content.onlinejacc.org/ on 12/16/2014
`
`ORTHOPHOENIX, LLC EXHIBIT 2001
`STRYKER CORPORATION V. ORTHOPHOENIX, LLC
`IPR2014-01519 Page 5 of 7
`
`

`

`26
`
`NAKAMURA ET AL.
`HIGH PRESSURE STENTING WITHOUT INTRAVASCULAR ULTRASOUND
`
`JACC Vol. 29, No. 1
`January 1997;21–7
`
`anticoagulation (3,4). The absence of vascular or bleeding
`complications in the present study is in distinct contrast to the
`7.1% and 13.5% vascular complication rates reported for these
`multicenter trials. More recently, other investigators have
`reported on the treatment with antiplatelet therapy and no
`Coumadin after stent implantation performed with angio-
`graphic evaluation only (17–21). Barragan et al. (17) reported
`a stent thrombosis rate of 4.2% and an incidence of vascular
`complications of 4.6% in 238 patients who were treated with
`ticlopidine (started 3 days before stent implantation) and a
`continuous heparin infusion for 24 h followed by low molecular
`weight heparin after the stent implantation procedure. The
`study was performed in an era when stent optimization with
`high pressure balloon inflation was not a standard practice. A
`strategy for treating only the ingress or the worst part of a
`dissection may also have partially contributed to the relatively
`high stent thrombosis rates. In contrast to the report of
`Barragan et al. (17), more recent reports on stent implantation
`performed without IVUS guidance and without anticoagula-
`tion appear to be more favorable (18–21). In these reports,
`poststent optimization was a standard practice, and patients
`received a combination of ticlopidine and aspirin (18–20).
`Morice, Cavalho and Jordan and their coauthors (18–20)
`separately report a stent thrombosis rate of 0% to 1.5% with
`a combination of
`ticlopidine (500 mg/day) and aspirin
`(325 mg/day) therapy for at least 1 month with low molecular
`weight heparin for 2 to 4 weeks. These studies were associated
`with vascular or bleeding complications up to 4.8%. Use of
`only ticlopidine and aspirin without low molecular weight
`heparin after a successful stent procedure reduces vascular
`complications without precipitating an increase in the inci-
`dence of stent thrombosis.
`As reported by Lablanche et al. (21), combination therapy
`for 3 months with only ticlopidine (500 mg daily) and aspirin
`(200 mg daily) in 98 patients after stent implantation resulted
`in 0% stent thrombosis events, a 1.0% incidence of vascular
`complications and a 1% rate of bleeding complications. Dif-
`ferences in absolute stent
`thrombosis rates between the
`present study and the more recent reports on treatment with
`ticlopidine and aspirin after stent implantation may be the
`result of differences in patient selection or other technical or
`procedure-related factors.
`Technical factors associated with stent thrombosis. The
`importance of technical factors during the stent implantation
`procedure in achieving both a high procedure success and low
`postprocedure stent thrombosis rates, irrespective of the post-
`stent implantation medical regimen, cannot be underesti-
`mated. Although the use of large or angiographically oversized
`balloons can also improve stent expansion, the consistent use
`of this strategy is associated with increased procedural compli-
`cations, including dissections and vessel rupture (10,12,22). A
`reduction in procedural complications during stent optimiza-
`tion was achieved when a strategy of using more appropriately
`sized balloons (balloon/artery ratio 1.0 to 1.1) for final stent
`optimization was used. In the present study, the importance of
`technical factors during the stent implantation procedure is
`
`revisited from a different perspective. Although the final stent
`percent diameter stenosis of 8 ⫾ 14% is similar to or better
`than most studies that employed only angiographic evaluation
`during the stent implantation procedure, it is less than the
`negative final percent diameter stenosis that was obtained
`when stent implantation was performed with IVUS guidance,
`which may have an impact on late angiographic or clinical
`results (3,4,9,12). The analysis of the factors associated with
`stent thrombosis illustrates that high pressure balloon dilations
`are not a panacea, particularly when undersized balloons are
`used for final poststent deployment optimization as demon-
`strated by the frequency distribution histograms of the final
`stent percent diameter stenosis, the final stent minimal lumen
`diameter and the balloon/artery ratio (Fig. 1). The use of an
`undersized balloon for final poststent deployment optimization
`resulted in a high residual final stent percent diameter stenosis
`and a significantly higher incidence of stent thrombosis. An
`undersized balloon was used for final stent optimization in all
`lesions with stent thrombosis. The association between a high
`residual final stent diameter stenosis and subsequent stent
`thrombosis is also consistent with previously published reports
`on stent implantation (23,24).
`Implications. It is important to put the results of the
`present study on stent implantation without IVUS guidance or
`subsequent anticoagulation therapy into a proper perspective
`in the present era of intracoronary stent implantation. Even
`with the reduction in vascular and bleeding complications, a
`stent thrombosis rate of 3.1% per patient remains relatively
`high, despite being comparable to the 3.5% incidence of stent
`thrombosis in several large multicenter trials on stent implan-
`tation (3,4). A decrease in the stent thrombosis rate will
`require more vigorous attention to optimizing stent expansion
`and covering flow-limiting dissections during the stent proce-
`dure. On-line quantitative coronary angiography may offer an
`improvement over visual angiographic estimation in the pre-
`cise assessment of the final angiographic percent diameter
`stenosis and may provide one means to further reduce stent
`thrombosis. In an unselected cohort of patients, routine IVUS
`after stent implantation may also help to reduce the stent
`thrombosis rates to a more acceptable rate. Alternatively, the
`selected use of IVUS may also benefit the resistant or complex
`lesions, long lesions and multiple stents, cohorts that histori-
`cally had a higher incidence of stent thrombosis. This strategy
`may be of help without prohibitively increasing procedural
`costs in all patients who undergo stent implantation. In addi-
`tion to the use of good stent technique, preliminary reports
`with heparin-coated stents appear to offer promise to reduce
`stent thrombosis rates to below 1%, which should be consid-
`ered the standard for an acceptable incide

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