Excimer Laser-Assisted Angioplasty CME Applications of the Power Pulse Spray Technique for The CIS “LACI Equivalent” Experience Page xx Acute Venous and Arterial Thrombosis Page xx

INSIGHT INTO THE DIAGNOSIS AND TREATMENT OF VASCULAR DISEASE MANAGEMENT OCTOBER 2004

Intracranial Middle Cerebral Artery Percutaneous Intervention Using a Drug-Eluting Stent

Jacqueline Saw, MD, Jay S. Yadav, MD, Cypher™ sirolimus-eluting stent (Cordis Cameron Haery, MD, Derk W. Krieger, MD, Corporation, Miami, Florida) on April 24, Alex Abou-Chebl, MD. 2003, it has rapidly become the dominant coro- Department of Cardiovascular Medicine and nary stent in use today in the United States. By Interventional Neurology, the Cleveland Clinic the end of 2003, approximately 350,000 Foundation, Cleveland, Ohio. patients in the US had received a Cypher stent, at th representing about half of all coronary stents tion ABSTRACT: The use of bare-metal stents for used.2 Its popularity is due to its marked reduc- pati intracranial vessels is associated with relatively tion of restenosis. The only reported use of advi high restenosis rates. We report the first human drug-eluting stents in intracranial vessels was in use of a sirolimus-eluting stent for a sympto- canine models.1 We report the first human use of matic proximal middle cerebral artery stenosis. a Cypher™ stent during percutaneous interven- This stent was successfully delivered and tion of an intracranial stenosis in the middle deployed without complications, with excellent cerebral artery (MCA). one month angiographic results. CASE REPORT Multidetector Computerized Tomography for Intracranial angioplasty and stenting are A 43 year-old Caucasian female with hyper- the Evaluation of Cerebrovascular Disease increasingly being used to treat patients with lipidemia, hypertension, and a twenty pack-year A Case Study recurrent cerebral ischemia due to intracranial history of smoking presented seven months ear- atherosclerosis, which is a cause of 8-10% of all lier with an infarct involving the right parietal Corey Goldman, MD, PhD ischemic strokes. Since there are no commer- lobe. Noninvasive imaging with transcranial Director of Vascular Medicine, Ochsner Heart cially available stents designed specifically for Doppler (TCD) ultrasound showed elevated and Vascular Institute, New Orleans, Louisiana the cerebral vasculature, all such procedures velocities in the right MCA (192 cm/s). Cerebral have utilized conventional coronary stenting angiography showed a diffuse diffuse 80% dis- The patient is a 59 yo hypertensive diabetic white male systems. However, the incidence of stent tal right internal carotid artery (RICA) stenosis ex-smoker with a history of CABG in 1994. In 1997, he restenosis in the intracranial circulation can be continued on page xx underwent insertion of a pacemaker for bradycardia. In up to 40%.1 Since the FDA approval of the ap 1999, he presented with hoarseness and was diagnosed pr with squamous cell laryngeal cancer by biopsy. He under- to went laryngeal irradiation from 3/99 to 5/99 and required Bivalirudin in Peripheral Vascular insertion of a PEG tube relating to his irradiation. He m stopped smoking at that time. He did well until 5/03, at Interventions: A Single Center Experience Ca which time he complained of some worsening dysphonia, Nicolas W. Shammas, MS, MD, *Jon H. Lemke, PhD, Eric J. Dippel, MD, *Dawn E. McKinney, dizziness and diplopia. Workup at that time revealed MA, Vickie S. Takes, RN, Monica Youngblut, RN, Melodee Harris, RN hypothyroidism that was successfully treated with levothy- roxin by 7/03/03. Despite that, he continued to have visu- ABSTRACT: Unfractionated received bivalirudin as the pri- limb loss, emergent need for al disturbance and changes in his voice. Interestingly, he is a widely utilized mary during revascularization of the same M complained of double vision only in his left visual field. An anticoagulant during peripher- PTA (0.75 mg/kg bolus, 1.75 vessel, embolic strokes, and tem ophthalmologic exam failed to explain his visual symptoms al angioplasty procedures mg/kg/h during the procedure). vascular complications (exact Ge and a neurological evaluation was suggested. (PTA). In contrast to heparin, Thirty-four (70.8%) had clau- 95% confidence intervals: continued on page xx bivalirudin is a direct dication and 6 (12.5%) had [0.0%,6.1%]). This compared inhibitor with predictable anti- ulceration. Thrombus was favorably to previously report- coagulation, does not activate angiographically seen in 3 ed data using unfractionated platelets, and inhibits both sol- (6.3%) patients. In-hospital heparin and the same serious uble and bound thrombin. serious procedural complica- procedural complications end- The experience with tions were limited to 2 (4.2%) points from our group at the bivalirudin during PTA (exact 95% confidence inter- same institution (9.2%). We remains limited. In this single- val: (0.5%,14.3%]) patients conclude that the use of center prospective study, 48 with major bleeding; none bivalirudin during PTA consecutive patients (60.4% (0.0%) of the other following continued on page xx males, mean age 70.0 ± 12.1) endpoints occurred: death, 18 V ASCULAR INTERVENTIONS OCTOBER 2004

Continued from page 1 2002 through August 6, 2002 at our Vascular Interventions institution, using bivalirudin as a pri- mary anticoagulant (0.75 mg/kg bolus, 1.75 mg/kg/hour during the appears feasible and safe. Large procedure) and did not meet one of the prospective registries are needed to following exclusion criteria: 1) confirm these findings. planned staged two or more peripher- This article is reprinted with permis- al procedures during the same hospital sion from the Journal of Invasive stay; 2) acute myocardial infarction Cardiology 2003;15:401-404. (MI) preceding the PTA; 3) the use of elective adjunctive intravenous glyco- Unfractionated heparin (UFH) is protein (GP) IIb/IIIa inhibitors during the current agent uti- the procedure; 4) concomitant coro- lized during peripheral angioplasty nary procedures; or 5) being on con- procedures (PTA). UFH has an unpre- tinuous intravenous heparin drip prior dictable anticoagulation response, is to the procedure. Clinical, angio- an indirect thrombin inhibitor, does graphic, and serious event rates were not inhibit bound thrombin and acti- collected prospectively. An interven- 1 vates platelets. We have recently tional cardiologist not involved in the Figure 1. Histogram for the overall age distribution and the current smokers' age distribution. reported our procedural complica- procedure adjudicated the in-hospital tions rate (9.2%) during PTA with the serious procedural complications use of UFH as a primary anticoagu- (SPC). SPC were defined as follows: The primary analysis of the study was Intraprocedural thrombus occurred lant.2 Our experience was in concor- • Major bleed: defined as requir- to estimate the rate of SPCs. in 6.3% of patients. Even though the dance with multiple published reports ing ≥ 2 units of PRBC transfu- Kruskal-Wallis tests were used to previous smokers were older than cur- showing a complication rate of sion, retroperitoneal bleed, or a compare age and body mass indices rent smokers, their durations of sur- 3.5–32.7%.3-9 drop of hemoglobin (Hb) after across pre-existing conditions. gery were similar. Any smoking (past Bivalirudin, a direct thrombin the procedure by more than 3 Kaplan-Meier plots and exact log- and current) had longer procedure inhibitor, has been recently shown to g/dL; rank tests were used to contrast proce- times (Figure 3). The difference in reduce both ischemic and bleeding •Vascular complications: defined dure times and lengths of stay. Fisher’s median procedure times was only 8 complications during coronary inter- as an AV fistula or pseudoa- exact tests were performed for com- minutes, but the difference is over an ventions when compared to UFH.10,11 neurysm after the procedure parisons of dichotomous and hour in the last quartiles of completed In contrast to UFH, bivalirudin has a when suspected clinically and unordered categorical variables. SPC procedures for the “never” versus short half-life, provides predictable confirmed by duplex ultra- rates are estimated with exact 95% “ever” smokers. The mean time of the anticoagulation response, and sound; confidence intervals. procedure was 82.4 minutes for inhibits free and bound thrombin. • Death due to procedural com- “never” smokers, but 108.1 minutes These properties provide potential plications; Results for the “ever” smokers. benefits over UFH during PTA where • Limb loss; Demographic and health history A total of 80 vessels were treated in thrombin activation is expected to •Need for in-hospital salvage characteristics of the population stud- 48 patients (mean of 1.7 vessels per be significant given the extent of ath- revascularization (angioplasty ied are shown in Table 1. Twenty nine patient). The 80 primary vessels treat- erosclerotic burden and large vessel or surgery) of the same treated (60.4%) patients were males. The ed were categorized as follows: size dilated with balloon angioplas- vessel; mean age was 70.0 ± 12.1 years; how- suprainguinal (n = 33), superficial ty. The short half-life of bivalirudin • Embolic stroke. ever, the age distribution is skewed femoral arteries and popliteal (n = 36), might also allow early sheath The following clinical variables with ages ranging from 41-89 and a and tibials (n = 11). The mean Ankle- removal, less bleeding complications were collected: age, gender, history of median age of 73 (Figure 1). There Brachial index was 0.7 ± 0.2. Closure than UFH, and a more reliable anti- diabetes, MI, angina, hypertension, were 32 (66.7%) patients with a doc- devices were used in 41 patients coagulation with no need for fre- hyperlipidemia, smoking (never, prior umented history of smoking (17 (85.4%). There were 90.2% of them quent activated clotting time (ACT) to the past year and within the past [35.4%]) current smokers, that is, who received the Perclose suturing measurements during long proce- year), prior cerebrovascular events, smoked within the past year). device and 9.8% who received dures. Early experience with body mass index, blood pressure at Embedded in the histogram is the age Angioseal. Forty-seven patients had an bivalirudin in the periphery has been onset of procedure, the presence of distribution of recent smokers. All ACT measured 10 minutes after the recently presented at scientific meet- peripheral vascular disease with patients below the age of 59 are cur- bivalirudin bolus. The ACTs were dis- ings.12-14 The data appear favorable ulceration, recent onset of claudica- rent smokers. In Figure 2, the boxplots tributed as follows: 38 (80.8%) > 400 showing low major bleeding rate tion (≤ 1 month), claudication ≤ 200 demonstrate how the age distribution seconds and 9 (19.2%) between 300- and adverse events compared to his- feet of walking, and pre-procedure for previous smokers is the same as the 399 seconds. toric data with UFH. In this single- ankle-brachial indices (ABI). The fol- never smokers and significantly differ- Overall, there were 2 (4.2% with a center experience, we report on our lowing angiographic criteria were ent from the current smokers. 95% confidence interval of in-hospital complication rate during collected: presence or absence of visi- Of these 48 patients, 35.4% (17) (0.5%,16.4%) of the patients with at PTA in 48 consecutive patients who ble thrombus during the intervention, had a history of heart disease (either least one SPCs, both of which were received bivalirudin as their primary ACT (10 minutes after bivalirudin MI, angina, or previous percutaneous major bleeding (Table 2). There were anticoagulant, and compare this rate bolus using the Hemochron coronary intervention) and 43.8% no deaths, amputations, urgent limb to a published historic control from machine), vessels treated and proce- (21) had diabetes. There were 12.5% salvage revascularization, vascular the same institution using the same dure time. The Institutional Review (6) of patients with lower leg ulcera- complications or embolic strokes. adverse events endpoints. Board of the Genesis Health System tion, 4.2% (2) of patients with a recent With bivalirudin, we are 95% confi- approved the protocol. onset of claudication (≤ 1 month), and dent that the true underlying SPC rate Methods Statistical analysis. Descriptive sta- 70.8% (34) of patients with sympto- for each of these none-occurring Forty-eight consecutive patients tistics on all variables are initially sum- matic claudication. Baseline pre-proce- underwent PTA from February 5, marized as proportions or mean ± SD. dure creatinine was 1.2 ± 0.6. continued on page xx 19

Figure 3. Kaplan-Meier plots of duration of procedure by the “ever” versus “never” Figure 2. Boxplot of the age distribution by smoking cohort. smoking status.

Continued from page 1 have ranged from 3.5-32.7% in sever- Vascular Interventions al published series.3-9 TABLE 1 The differences between smoking PATIENTS’ DEMOGRAPHICS AND HEALTH HISTORY events and these two physicians is less history cohorts make it difficult to ON PRESENTATION than 6.1%. make global claims across all patients, as well as difficult to simply estimate Age (mean ± SD) 70.0 ± 12.1 Discussion the effect of accepted risk factors on Body mass index (mean ± SD) 27.8 ± 4.1 In this single-center experience SPCs. It is likely that the much older Highest heart rate prior to procedure (mean + SD) 72.2 ± 11.4 from February 5, 2002 through previous smokers quit a long time ago. Male (%) 60.4 August 6, 2002, we had two experi- This is one of many survivorship Peripheral vascular disease with ulceration (%) 12.5 enced peripheral interventionalists effects; older patients continue to have Claudication < 1 month of presentation (%) 4.2 (each of the 2 experienced operators fewer co-morbid conditions, especially Claudication < 200 feet 70.8 has performed a minimum of 200 histories of cardiovascular diseases. New York Class (%) peripheral procedures) who used The safer profile of bivalirudin over I 93.7 bivalirudin exclusively during PTA. heparin during percutaneous proce- II 6.3 The overall complication rate with dures has been shown in several stud- III & IV 0.0 bivalirudin in this series was 4.2% (2 ies. In the Bivalirudin Angioplasty History of MI (%) 18.8 Prior history of angina (%) 33.3 patients out of 48 met at least one of Trial (BAT),10 bivalirudin reduced the Previous PCI (%) 26.7 the endpoints). Previously, we have risk of bleeding by 62% when com- History of hypertension requiring treatment (%) 85.4 reported that peripheral vascular com- pared to UFH (p < 0.001). The History of smoking (%) 11 plications are not trivial with unfrac- recently published Replace-2 trial Never smoked 33.3 tionated heparin as the base anticoag- also showed a major bleeding rate of Smoked > 1 year ago 31.3 ulant (SPCs were 9.2% using the same 2.4% in the bivalirudin arm versus Smoked < 1 year ago 35.4 definitions as in this study).2 Our in- 4.1% in the heparin plus GP IIb/IIIa Family history of CAD (%) 27.7 hospital outcomes with bivalirudin arm (p < 0.001). A recent meta-analy- Hypercholesterolemia requiring treatment (%) 83.0 during PTA compare favorably with sis by Yusuf et al.15 has shown that History of diabetes (%) 43.8 UFH. The complication rate appeared bivalirudin has a significant advan- Baseline creatinine value (mean ± SD) 1.2 ± 0.6 doubled with UFH when compared to tage over UFH in reducing major Prior cerebrovascular disease (%) 23.4 bivalirudin. This is also in concor- bleeding during percutaneous proce- dance with data recently reported in dures. Our preliminary experience scientific meetings.12-14 Grubbs and col- and others seem to support the safety TABLE 2 leagues12 reported their experience of bivalirudin during PTA proce- DESCRIPTIVE STATISTICS FOR SERIOUS with 69 PTA patients receiving dures. A large registry or a random- PROCEDURAL COMPLICATIONS bivalirudin as a primary anticoagu- ized trial against UFH during PTA is lant. In their series, there were no now needed to confirm these small Serious Procedural % (N) Exact 95% CI* adverse events reported, including no observations. Complications major bleeding, acute thrombosis, or Limitations of this study. This is a Death 0.0% (0) [0.0%,6.1%] death. Knopf et al.13 also reported on single center experience and might not Limb loss 0.0% (0) [0.0%,6.1%] 72 patients receiving bivalirudin dur- be shared by other operators. The data Bleeding (major) 4.2% (2) [0.5%,14.3%] ing PTA. There were no deaths, major is preliminary and needs to be validat- Revascularization needed 0.0% (0) [0.0%,6.1%] bleeding, strokes, or distal emboliza- ed in a large, multi-center prospective Embolic Stroke 0.0% (0) [0.0%,6.1%] tion in their series. Furthermore, Allie study. Nevertheless, this study was Vascular complications 0.0% (0) [0.0%,6.1%] et al.14 have used bivalirudin in 180 prospective and data collection was Patients who had any renals and 75 iliac interventions with timely and accurate. Although the of the above complications 4.2% (2) [0.5%,14.3%] no major complications reported. In * CI = confidence interval contrast, complication rates with UFH continued on page xx 20 V ASCULAR INTERVENTIONS OCTOBER 2004

Continued from page 1 References patient age. Br J Radiol 1991;64:5-9. peripheral vascular interventions: Vascular Interventions 1. Marmur JD. Direct versus indirect 7. Hasson JE, Acher CW, Wojtowycz M, et Possible benefits over unfractionated thrombin inhibition in percutaneous al. Lower extremity percutaneous trans- heparin. Poster presented at coronary intervention. J Invas Cardiol luminal angioplasty: Multifactorial Cardiovascular Revascularization 2002;14(Suppl B):8B-18B. analysis of morbidity and mortality. Therapy conference; January 26-29, sample size is small, this manuscript 2. Shammas NW, Lemke JH, Dippel EJ, et Surgery 1990;108:748-752. 2003, Washington, D.C. adds to the current limited experience al. In-hospital complications of periph- 8. Boyer L, Therre T, Garcier JM, et al. 13. Knopf W. Joseph’s Hospital experience: with bivalirudin during PTA. eral vascular interventions using unfrac- Infrapopliteal percutaneous translumi- Direct thrombin inhibitors in ACS and tionated heparin as the primary antico- nal angioplasty for limb salvage. Acta PCI: The case for bivalirudin replacing Radiol 2000;41:73-77. unfractionated heparin in PCI. Paper pre- Acknowledgment. The authors agulant. J Invas Cardiol 2003;15:242- 246. 9. Greenfield AJ. Femoral, popliteal, and sented at Transcatheter Cardiovascular wish to thank Peter Teuber, PhD, for 3. Matsi PJ, Manninen HI. Complications tibial arteries: Percutaneous translumi- Therapeutics 14th Annual Scientific his valuable input in this study and the of lower-limb percutaneous translumi- nal angioplasty. Am J Roentgenol Symposium; September 24-28, 2002; manuscript. nal angioplasty: A prospective analysis 1980;135:927-935. Washington, D.C. ■ of 410 procedures on 295 consecutive 10. Bittl JA, Chaitman BR, Feit F, et al. 14. Allie D. Bivalirudin as sole anticoagu- patients. Cardiovasc Intervent Radiol Bivalirudin versus heparin during coro- lant in peripheral vascular disease: A nary angioplasty for unstable or postin- safe and feasible alternative in renal and Reprinted with permission from The 1998;21:361-366. 4. Gutteridge W, Torrie EP, Galland RB. farction angina: Final report reanalysis iliac interventions. Presented at Journal of Invasive Cardiology. Cumulative risk of bypass, amputation of the Bivalirudin Angioplasty Study. American College of Cardiology 52nd or death following percutaneous translu- Am Heart J 2001;142:952-959. Annual Scientific Session; March 30- Authors’ affiliation: Genesis Heart minal angioplasty. Eur J Vasc Endovasc 11. Lincoff AM, Bittl JA, Harrington RA, et April 2, 2003, Chicago, IL. Institute, Cardiovascular Medicine, Surg 1997;14:134-139. al. Bivalirudin and provisional glyco- 15. Direct Thrombin Inhibitor Trialists' P.C., and the *Genesis Health System, 5. Axisa B, Fishwick G, Bolia A, et al. protein IIb/IIIa blockade compared with Collaborative Group. Direct thrombin Davenport, Iowa. Complications following peripheral heparin and planned glycoprotein inhibitors in acute coronary syndromes: angioplasty. Ann R Coll Surg Engl IIb/IIIa during percutaneous coronary principal results of a meta-analysis *Supported in part by a grant from the 2002;84:39-42. intervention; The REPLACE-2 random- based on individual patients' data. Genesis Foundation 6. Morse MH, Jeans WD, Cole SE, et al. ized trial. JAMA 2003;289:853-863. Lancet 2002;359:294-302. Complications in percutaneous translu- 12. Grubbs G. Single center experience minal angioplasty: Relationships with with bivalirudin anticoagulation in

Commentary In this pooled analysis, complications with UFH were as follows: early occlusion (3.1%), emboliza- Bivalirudin in Peripheral tion (2.3%), vascular complications (0.7%), major bleed (2.1%), renal failure (1.7%), death (1.6%), Vascular Intervention limb loss (1.9%), in-situ thrombosis (2.6%), stroke (0.4%), and myocardial infarction (0.7%). The 30- Nicolas W. Shammas, MS, MD day limb loss and mortality for limb ischemia Genesis Heart Institute, Cardiovascular Medicine, P.C., Davenport, Iowa patients were higher than claudicants (9.1% versus 0.2 % and 2.3% versus 0.1% respectively). This ercutaneous peripheral vascular procedures prospective and 23 retrospective) published in the analysis indicates the wide and significant range of Phave increased exponentially over the past 10 literature from 1980 to 2000 in order to better complications seen during PVI in patients receiving years. Anderson et al.1 reported a 979% growth in define the various complication rates during PVI UFH as a primary anticoagulant and warrants a peripheral vascular interventions since 1995, with with UFH as a primary anticoagulant.5 All compli- search for a better and safer replacement. a simultaneous drop in the number of surgical vas- cations within 30 days of PVI were recorded. Only cular procedures. Despite the sharp rise in periph- lower extremity and renal procedures were includ- Bivalirudin in PVI eral vascular interventions (PVI), complication ed. Patients who received a primary anticoagulant Bivalirudin, a direct thrombin inhibitor, is a rates have continued to be significant and, in fact, other than UFH were excluded. Death, stroke, 20-amino acid synthetic peptide that inhibits limb loss has trended upwards.1 myocardial infarction, major bleed (> 3 gm/dl loss thrombin directly by binding to both its catalytic of hemoglobin, retroperitoneal bleed and bleed site and anion-binding exocite. It produces a There are many potential predictors of compli- requiring > 2 units of packed RBC transfusion), dose-dependent prolongation of the ACT with an cations in PVI. These predictors potentially include renal failure, and limb loss were calculated with almost immediate anticoagulant activity follow- the state of the limb (rest ischemia versus claudica- the patient number as the denominator. Distal ing an intravenous injection. The elimination tion), distal runoff, lesion characteristics (length, embolization, early occlusion, in-situ thrombosis, half-life of bivalirudin is approximately 25 min- occlusion vs. stenosis, location), intraprocedural vascular complications (pseudoaneurysms and AV utes in patients with normal renal function. thrombus, renal insufficiency, age, gender, smoking fistula) were calculated with the number of vessels history, procedure length, number of lesions and angioplastied as the denominator. In contrast to UFH, bivalirudin has a short vascular beds treated in one setting, and the pres- half-life, provides predictable anticoagulation ence of various comorbidities (diabetes and coro- The total number of patients reported in this response, and inhibits free and bound thrombin nary artery disease). Until recently,2,3 the choice of study was 7545 (64.5% males), and the number as well as thrombin-induced platelet activation, the anticoagulant has not been considered as a of vessels angioplastied was 9489. Infrainguinal aggregation and granule release.6 These properties potential predictor of complications in PVI. treatment and total occlusions accounted for might provide potential benefits over UFH during 60.9% and 30.8% of all vessels, respectively. PTA where thrombin activation is expected to be Unfractionated Heparin in PVI There was a high proportion of rest limb ischemia significant, given the extent of atherosclerotic Despite changes in techniques and equipment in (58.1%), diabetics (38.4%), and coexisting coro- burden and large vessel size dilated with balloon the angiographic suite, the use of unfractionated nary artery disease (41.9%) in these peripheral angioplasty. Furthermore, the short half-life of heparin (UFH) has remained the most widely uti- vascular patients. The overall reported success bivalirudin might also allow early sheath lized and unchallenged during PTA.4 rate was 89.2% (93.2% for stenosis and 71.7% removal, less bleeding complications than UFH, We have recently pooled data from 39 studies (15 for occlusions). continued on page xx 21

Continued from page xx unfractionated heparin in PCI. Paper presented at Transcatheter Cardiovascular Therapeutics 14th Annual Scientific Commentary Given the heterogeneous patient populations in Symposium; September 24-28, 2002;Washington D.C. 10. Shammas NW, Lemke JH, Dippel EJ, McKinney DE, Takes VS, both the bivalirudin and UFH groups, and the Youngblut M, Harris M. Bivalirudin in peripheral vascular inter- and a more reliable anticoagulation, with no need potential selection bias, a randomized, double- ventions: a single center experience. J Invasive Cardiol. 2003;15:401-404 for frequent ACT measurements during long pro- blind trial of bivalirudin versus UFH is warranted. cedures.7, 8 Early data with bivalirudin is promising, but ran- Several small studies have evaluated domized studies are needed to determine whether bivalirudin in PVI with encouraging findings.3, 8-10 this pharmacologic agent is superior to UFH. Recently, data from the APPROVE (Angiomax Peripheral Procedure Registry of Vascular Events) The author can be contacted at: multi-center registry (25 US centers, 505 patients) [email protected] was presented by Dr. David Allie, primary inves- tigator, at a recent scientific meeting. In this reg- Dr. Shammas discloses that he is a member of istry, bivalirudin was utilized as the primary anti- the speakers bureau and has received a research coagulant in PVI of renal, iliac and femorals. The grant from The Medicines Company. REPLACE-2 dose was utilized, and consisted of ■ an 0.75 mg/kg intravenous bolus, followed by 1.75 mg/kg/hour infusion during the length of the References 1. Anderson PL, Gelijns A, Moskowitz A, Arons R, Gupta L, procedure. The data from APPROVE appears Weinberg A, Faries PL, Nowygrod R, Kent KG. Understanding consistent with previously published bivalirudin trends in inpatient surgical volume: vascular interventions, 1980-2000. J Vasc Surg 2004;39:1200-8 data in the periphery where the composite inci- 2. Shammas NW, Lemke JH, Dippel EJ, McKinney D, Takes VS, dence of death, limb loss, unplanned urgent revas- Youngblut M, Harris M, Harb C, Kapalis MJ, Holden J. In-hos- pital complications of peripheral vascular interventions using cularization, and major bleeding appears favor- unfractionated heparin as the primary anticoagulant. J Invasive able compared to the historic control UFH. A Cardiol. 2003;15(5):242-6 3. Allie DE, Lirtzman MD, Wyatt CH, Keller VA, Khan MH, Khan pooled analysis of published and presented data MA, Fail PS, Hebert CJ, Ellis SD, Mitran E, Chaisson G, Stagg on bivalirudin in PVI is shown in Table 1. S Jr, Allie AA, Walker CM. Bivalirudin as a foundation antico- agulant in peripheral vascular disease: a safe and feasible alter- native for renal and iliac interventions. J Invasive Cardiol. 2003 Jun;15(6):334-42. The bivalirudin group (n= denominator of 4. Shammas NW. An overview of in peripheral vas- patients’ number with available data) consisted cular interventions. J Invasive Cardiol. 2004;16(8):440-3. 5. Shammas NW, Dippel EJ, Lemke JH. Complications of periph- of 38.2% diabetics (n=808 patients), 36.4% with eral interventions with unfractionated heparin. Presented as an history of coronary artery disease (n=807), abstract at Cardiovascular Interventions and Practice Guidelines Scientific Sessions 2004, Lincolnshire, Illinois, August 5-6, 72.2% suprainguinal vessels (n=832) with 2004. In Shammas NW; Cardiovascular Interventions and 46.4% renals (n=760). Unfortunately, a clear dis- Practice Guidelines 2004 proceedings handbook, Midwest Cardiovascular Research Foundation, page 300. tinction between claudicants and limb ischemia 6. Marmur JD. Direct versus indirect thrombin inhibition in percu- patients was available only on a small number of taneous coronary intervention. J Invasive Cardiol 2002;14 (Suppl B):8B-18B patients (n=123, excluding renals) and was 7. Direct Thrombin Inhibitor Trialists' Collaborative Group. Direct thrombin inhibitors in acute coronary syndromes: principal 4.9%. It is clear, however, that the early experi- results of a meta-analysis based on individual patients' data. ence with bivalirudin seems to be in a low risk Lancet 2002;359:294-302 8. Grubbs G. Single center experience with bivalirudin anticoagu- population (mostly suprainguinal with a low per- lation in peripheral vascular interventions: possible benefits centage of limb ischemia patients), which could over unfractionated heparin. Poster presented at Cardiovascular Revascularization Therapy conference;January 26-29, 2003, explain some of the complication differences Washington , D.C. between it and UFH. 9. Knopf W. Joseph’s Hospital experience: Direct thrombin inhibitors in ACS and PCI: the case for bivalirudin replacing

TABLE 1 IN-HOSPITAL COMPLICATIONS OF PVI USING BIVALIRUDIN AS A PRIMARY ANTICOAGULANT

Author Patients Vessels Success Death Limb Major Acute loss Bleeding Thrombosis

Grubbs * 28 28 27 0 0 0 0 Knopf† 72 88 88 0 0 0 0 Allie# 255 255 255 0 0 4 0 Shammas^ 48 80 80 0 0 2 0 APPROVE trial 505 505 475 0 1 12 2

Total 908 956 925 0 1 18 2 Percent - - 96.76 0 0.11 1.98 0.21

* only non-AAA, non--carotid arterial interventions included ; number of vessels and patients presumed the same † no distinction between lesions and vessels # Major bleed in all 4 patients was a hematoma>5 cm with no apparent transfusions needed. ^ Major bleeding defined as >3 gm/dl Hb drop, 2 or more units of PRBC transfusion, Intracranial bleed or retroperiteoneal bleed, similar to protocol definition of APPROVE AAA=Abdominal Aortic Aneurysm