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Comparison of aspirin alone versus aspirin plus ticlopidine after coronary artery stenting
Comparison of Aspirin Alone Versus Ticlopidine After Coronary Artery
Aspirin Plus Stenting
Christopher M. Goods, MB, BS, Khaled F. Al-Shaibi, MB, CHB, Ming W. Liu, MD, Jay S. Yadav, MD, Atul Mathur, MD, Suresh P. Jain, MD, Larry S. Dean, MD, Sriram S. lyer, MD, J. Michael Parks, MD, and Gary S. Roubin, MD, PhD
ecent studies have demonstrated that antiplatelet R therapy using a combination of aspirin and ticlopidine without anticoagulation after native coronary artery stenting is associated with a low incidence of stent thrombosis (< 1%) and a low incidence of bleeding and vascular access complications. ‘x2The use of this antiplatelet regimen is rapidly becoming standard practice. Ticlopidine, however, may cause significant adverse reactions, in particular neutropenia3s4;this makes extra physician and laboratory monitoring necessary and increases the cost of the procedure. Currently, it is not known if antiplatelet therapy with aspirin alone would be as effective as the combination of aspirin and ticlopidine in preventing stent thrombosis. The purpose of this prospective comparative study was to determine whether aspirin alone would be as affective as aspirin and ticlopidine in preventing stent thrombosis after stenting of native coronary arteries. ... In‘ September 1994, we began prospectively evaluating patients who had undergone stenting of native coronary arteries, and who received a poststenting protocol of antiplatelet therapy with aspirin + ticlopidine without anticoagulation. Patients were selected for this protocol after satisfying certain angiographic criteria. These criteria included: adequate coverage of intimal dissections, absence of residual filling defects, and normal flow in the stented vessel at the end of the procedure. From September 1994 through October 1995, 338 patients were managed with this protocol. In July 1995, following the success of this protocol and in attempt to further simplify poststenting management, a prospective comparative study of stent patients managed with aspirin alone without anticoagulation was begun. The angiographic selection criteria were equivalent for both antiplatelet protocols. From July through September 1995,46 patients were selected for this protocol. Selection to either protocol was not randomized but was based on physician preference. Patients were selected to either protocol by the same group of angioplasty operators. Recruitment of patients to the aspirin-only group was stopped in September 1995, because of a high incidence of adverse outcomes in this group. Both groups of patients received the flexFrom the Cardiovascular Division, University of Alabama at Birmingham. Birminaham. Alabama. Dr. Roubin’s address is: Division of Cardiovbscular\isedses, University of Alabama at Birmingham, 1808 7th Avenue South, 383 BDB, Birmingham, Alabama 35294. Manuscript received March 25, 1996; revised manuscript received and accepted May 17, 1996.
1042
0 1996 by Excerpto Medica, All rights reserved.
Inc.
ible coil stent (Cook, Inc.). These 2 groups constitute the study population. All patients in the aspirin group received soluble aspirin 325 mg before the procedure. Aspirin was continued at a dose of 325 mg twice daily for 30 days at which time the dose of aspirin was reduced to 325 mg/day. Patients in the aspirin + ticlopidine group received soluble aspirin 325 mg and ticlopidine 250 mg before the procedure. Aspirin 325 mg twice daily and ticlopidine 250 mg twice daily were continued for 30 days after which patients were managed with aspirin 325 mg/day. During the procedure, patients in both groups received heparin administered by intra-arterial injection and the dose was adjusted to achieve an activated clotting time between 250 and 350 seconds. All patients received intravenous nitroglycerin during the procedure. Generally, intravenous heparin was not administered after the procedure. For reasons including recent myocardial infarction, the presence of suspected thrombus after coronary balloon angioplasty, or a bailout indication for stenting, 4 patients (9%) in the aspirin group and 39 (12%) in the aspirin + ticlopidine group (p = 0.2) received intravenous heparin for a period of 12 to 48 hours after the procedure. No patient in either group received warfarin. Patients in the aspirin and ticlopidine group had white blood cell estimations performed after 2 weeks of therapy with ticlopidine. Coronary angioplasty was performed using conventional techniques and 8Fr (ID 0.086 inches) guide catheters via the femoral approach. Coronary lesions were dilated using balloon catheters equivalent to target vessel size. Stent size was selected for a stentto-artery ratio of 1.1: 1.2: 1 according to current recommendations.5 Stents were deployed using stent balloon inflation pressures of 4 to 6 atm. In all patients, high pressure balloon inflations were performed after stenting using a noncompliant balloon equivalent in size to the nominal size of the stent. Adequacy of stent placement was assessed angiographically. The result was considered inadequate if dissection flaps were not completely covered by stent struts, or if residual filling defects were present within the stented segment, or if flow was less than that of the Thrombolysis in Myocardial Infaction (TIMI) trial III in the stented vessel. In these patients, further high pressure balloon inflations were performed and/or additional stents deployed. Intravascular ultrasound was not used in any patient to ascertain adequacy of stent deployment. Patients were allowed to mobilize 10 to 12 hours after arterial sheath removal. If they remained stable they were 0002.9149/96/S 15.00 PI1 50002.9149(96)00532-2
infarction in the distribution of the stented vessel. Non-Q-wave myoAspirin + Ticlopidine Aspirin cardial infarction was defined as [n = 338) [n = 46) p Value creatinine phosphokinase (CK) elevation over twice 250 IU/L with a Age ly4 602 11 63 t 11 0.08 Mole 246 (73) 27 (59) 0.07 positive CK-MB isoenzyme. Recent Previous balloon ongioplosty 128 (38) 16 (35) 0.8 myocardial infarction was defined Previous bypass 56 (17) 7 (15) 0.9 coronary as that occurring
I
Patient
Characteristics
BRIEFREPORTS 1043
aspirin + ticlopidine group had acute or threatened closure after coronary balloon angioplasty as an indication for stenting (p
1044
THE AMERICAN JOURNAL OF CARDIOLOGY@
VOL. 78
Recently, Hall et al” reported the results of a small randomized study comparing aspirin alone with the combination of aspirin and ticlopidine following intravascular ultrasound-guided stenting. The rate of stent thrombosis was higher in the aspirin-only group than in the aspirin and ticlopidine group (2.9% vs 0.8%), although because this study was underpowered, these results did not reach statistical significance (p = 0.2). This evidence along with the results of our study suggest that aspirin alone is not as effective as aspirin and ticlopidine in preventing stent thrombosis.
This prospective nonrandomized study demonstrated an increased incidence of stent thrombosis, Q-wave myocardial infarction, and cardiac death in a group of patients managed with aspirin alone compared with a group of patients managed with the combination of aspirin and ticlopidine following native coronary artery stenting. 1. Colombo A, Hall P, Nakamura S, Ahuagor Y, Maiello L, Martini G, Gaglione A, Goldberg SL, Tobis J, Intracoronaxy stenting without anticoagulation accomplished with intravascular ultrasound guidance. Circulation 1995;91:16761688. 2. Goods CM, Al-Shaibi KF, Yadav SS, Liu MW, Negus BH, Iyer SS, Dean LS, Jain SP, Baxley WA, Parks.JM, Sutor RJ, Roubin GS. Utilization of the coronary balloon-expandable coil stent without anticoagulation or intravascular ultrasound. Circuladon; in press. 3. Gent M. Blakelv JA. EastonJD. Ellis DJ. Hachinski VC. Harbison JW. Panak E, Roberts RS, S&ella J, Turpie AGG. The Canadian kmerican ticlipidine study in thromboembolic stroke. Lancer 1989;1215- 1220. 4. HassWK, EastonJD, Adams HP Jr, Ptyse-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 Eng[ .I Med 1989;321:501-507. 5. Ho DSW, Liu MW, Iyer S, Parks JM, Roubin GS. Sizing the GianturcoRoubin coronary flexible coil stent. C&et Cardiovasc Diagn 1994;32:242248.
6. Morice MC, Amor M, Benveniste E, Bunouf P, Cribier A, Labnmie P, Masquet C, Petiteau. Coronary stenting without coumadin phaseII, III, IV, V. Predictors of major complications (abstr). Circulation 1995;92(supplI):I-795. 7. Nath FC, Muller DWM, Ellis SG, Rosenscbein U, Chapekis A, Quain L, Zimmerman C, Topol EJ. Thrombosis of a flexible coil stent: frequency, predictors and clinical outcome. JAm Co11Cardiol 1993;21:622-627. 8. Sutton JM, Ellis SG, Roubin GS, Pinkerton CA, King SB, Raizner AE, Holmes DR. Kereiakes DJ, Topol ET.Major clinical events after coronary stenting: the multicenter registry of acute and elective Gianturco-Roubin stent placement. Circulation 1994:89:1126-l 137. 9. Herrmann HC, Buchbinder M, Clemen MW, FischmanD, Goldberg S, Leon MB, Schatz RA, Tierstein P, Walker CM, Hirshfeld JW. Emergentuse of balloon-expandable coronary artery stenting for failed percutaneoustransluminal coronary angioplasty. Circulahm 1992;86:812-819. 10. Hall P, Nakamura S, Maiello L, Itob A, Blengino S, Martini G, Ferraro M, Colombo A. A randomized comoarison of combined ticlooidine and asoirin therapy versus aspirin therapy alone after successful intravascular ultrasdundguided stent implantation. Circulation 1996;93:215-222.
NOVEMBER 1, 1996
Aspirin Plus Stenting
Christopher M. Goods, MB, BS, Khaled F. Al-Shaibi, MB, CHB, Ming W. Liu, MD, Jay S. Yadav, MD, Atul Mathur, MD, Suresh P. Jain, MD, Larry S. Dean, MD, Sriram S. lyer, MD, J. Michael Parks, MD, and Gary S. Roubin, MD, PhD
ecent studies have demonstrated that antiplatelet R therapy using a combination of aspirin and ticlopidine without anticoagulation after native coronary artery stenting is associated with a low incidence of stent thrombosis (< 1%) and a low incidence of bleeding and vascular access complications. ‘x2The use of this antiplatelet regimen is rapidly becoming standard practice. Ticlopidine, however, may cause significant adverse reactions, in particular neutropenia3s4;this makes extra physician and laboratory monitoring necessary and increases the cost of the procedure. Currently, it is not known if antiplatelet therapy with aspirin alone would be as effective as the combination of aspirin and ticlopidine in preventing stent thrombosis. The purpose of this prospective comparative study was to determine whether aspirin alone would be as affective as aspirin and ticlopidine in preventing stent thrombosis after stenting of native coronary arteries. ... In‘ September 1994, we began prospectively evaluating patients who had undergone stenting of native coronary arteries, and who received a poststenting protocol of antiplatelet therapy with aspirin + ticlopidine without anticoagulation. Patients were selected for this protocol after satisfying certain angiographic criteria. These criteria included: adequate coverage of intimal dissections, absence of residual filling defects, and normal flow in the stented vessel at the end of the procedure. From September 1994 through October 1995, 338 patients were managed with this protocol. In July 1995, following the success of this protocol and in attempt to further simplify poststenting management, a prospective comparative study of stent patients managed with aspirin alone without anticoagulation was begun. The angiographic selection criteria were equivalent for both antiplatelet protocols. From July through September 1995,46 patients were selected for this protocol. Selection to either protocol was not randomized but was based on physician preference. Patients were selected to either protocol by the same group of angioplasty operators. Recruitment of patients to the aspirin-only group was stopped in September 1995, because of a high incidence of adverse outcomes in this group. Both groups of patients received the flexFrom the Cardiovascular Division, University of Alabama at Birmingham. Birminaham. Alabama. Dr. Roubin’s address is: Division of Cardiovbscular\isedses, University of Alabama at Birmingham, 1808 7th Avenue South, 383 BDB, Birmingham, Alabama 35294. Manuscript received March 25, 1996; revised manuscript received and accepted May 17, 1996.
1042
0 1996 by Excerpto Medica, All rights reserved.
Inc.
ible coil stent (Cook, Inc.). These 2 groups constitute the study population. All patients in the aspirin group received soluble aspirin 325 mg before the procedure. Aspirin was continued at a dose of 325 mg twice daily for 30 days at which time the dose of aspirin was reduced to 325 mg/day. Patients in the aspirin + ticlopidine group received soluble aspirin 325 mg and ticlopidine 250 mg before the procedure. Aspirin 325 mg twice daily and ticlopidine 250 mg twice daily were continued for 30 days after which patients were managed with aspirin 325 mg/day. During the procedure, patients in both groups received heparin administered by intra-arterial injection and the dose was adjusted to achieve an activated clotting time between 250 and 350 seconds. All patients received intravenous nitroglycerin during the procedure. Generally, intravenous heparin was not administered after the procedure. For reasons including recent myocardial infarction, the presence of suspected thrombus after coronary balloon angioplasty, or a bailout indication for stenting, 4 patients (9%) in the aspirin group and 39 (12%) in the aspirin + ticlopidine group (p = 0.2) received intravenous heparin for a period of 12 to 48 hours after the procedure. No patient in either group received warfarin. Patients in the aspirin and ticlopidine group had white blood cell estimations performed after 2 weeks of therapy with ticlopidine. Coronary angioplasty was performed using conventional techniques and 8Fr (ID 0.086 inches) guide catheters via the femoral approach. Coronary lesions were dilated using balloon catheters equivalent to target vessel size. Stent size was selected for a stentto-artery ratio of 1.1: 1.2: 1 according to current recommendations.5 Stents were deployed using stent balloon inflation pressures of 4 to 6 atm. In all patients, high pressure balloon inflations were performed after stenting using a noncompliant balloon equivalent in size to the nominal size of the stent. Adequacy of stent placement was assessed angiographically. The result was considered inadequate if dissection flaps were not completely covered by stent struts, or if residual filling defects were present within the stented segment, or if flow was less than that of the Thrombolysis in Myocardial Infaction (TIMI) trial III in the stented vessel. In these patients, further high pressure balloon inflations were performed and/or additional stents deployed. Intravascular ultrasound was not used in any patient to ascertain adequacy of stent deployment. Patients were allowed to mobilize 10 to 12 hours after arterial sheath removal. If they remained stable they were 0002.9149/96/S 15.00 PI1 50002.9149(96)00532-2
infarction in the distribution of the stented vessel. Non-Q-wave myoAspirin + Ticlopidine Aspirin cardial infarction was defined as [n = 338) [n = 46) p Value creatinine phosphokinase (CK) elevation over twice 250 IU/L with a Age ly4 602 11 63 t 11 0.08 Mole 246 (73) 27 (59) 0.07 positive CK-MB isoenzyme. Recent Previous balloon ongioplosty 128 (38) 16 (35) 0.8 myocardial infarction was defined Previous bypass 56 (17) 7 (15) 0.9 coronary as that occurring
I
Patient
Characteristics
BRIEFREPORTS 1043
aspirin + ticlopidine group had acute or threatened closure after coronary balloon angioplasty as an indication for stenting (p
1044
THE AMERICAN JOURNAL OF CARDIOLOGY@
VOL. 78
Recently, Hall et al” reported the results of a small randomized study comparing aspirin alone with the combination of aspirin and ticlopidine following intravascular ultrasound-guided stenting. The rate of stent thrombosis was higher in the aspirin-only group than in the aspirin and ticlopidine group (2.9% vs 0.8%), although because this study was underpowered, these results did not reach statistical significance (p = 0.2). This evidence along with the results of our study suggest that aspirin alone is not as effective as aspirin and ticlopidine in preventing stent thrombosis.
This prospective nonrandomized study demonstrated an increased incidence of stent thrombosis, Q-wave myocardial infarction, and cardiac death in a group of patients managed with aspirin alone compared with a group of patients managed with the combination of aspirin and ticlopidine following native coronary artery stenting. 1. Colombo A, Hall P, Nakamura S, Ahuagor Y, Maiello L, Martini G, Gaglione A, Goldberg SL, Tobis J, Intracoronaxy stenting without anticoagulation accomplished with intravascular ultrasound guidance. Circulation 1995;91:16761688. 2. Goods CM, Al-Shaibi KF, Yadav SS, Liu MW, Negus BH, Iyer SS, Dean LS, Jain SP, Baxley WA, Parks.JM, Sutor RJ, Roubin GS. Utilization of the coronary balloon-expandable coil stent without anticoagulation or intravascular ultrasound. Circuladon; in press. 3. Gent M. Blakelv JA. EastonJD. Ellis DJ. Hachinski VC. Harbison JW. Panak E, Roberts RS, S&ella J, Turpie AGG. The Canadian kmerican ticlipidine study in thromboembolic stroke. Lancer 1989;1215- 1220. 4. HassWK, EastonJD, Adams HP Jr, Ptyse-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 Eng[ .I Med 1989;321:501-507. 5. Ho DSW, Liu MW, Iyer S, Parks JM, Roubin GS. Sizing the GianturcoRoubin coronary flexible coil stent. C&et Cardiovasc Diagn 1994;32:242248.
6. Morice MC, Amor M, Benveniste E, Bunouf P, Cribier A, Labnmie P, Masquet C, Petiteau. Coronary stenting without coumadin phaseII, III, IV, V. Predictors of major complications (abstr). Circulation 1995;92(supplI):I-795. 7. Nath FC, Muller DWM, Ellis SG, Rosenscbein U, Chapekis A, Quain L, Zimmerman C, Topol EJ. Thrombosis of a flexible coil stent: frequency, predictors and clinical outcome. JAm Co11Cardiol 1993;21:622-627. 8. Sutton JM, Ellis SG, Roubin GS, Pinkerton CA, King SB, Raizner AE, Holmes DR. Kereiakes DJ, Topol ET.Major clinical events after coronary stenting: the multicenter registry of acute and elective Gianturco-Roubin stent placement. Circulation 1994:89:1126-l 137. 9. Herrmann HC, Buchbinder M, Clemen MW, FischmanD, Goldberg S, Leon MB, Schatz RA, Tierstein P, Walker CM, Hirshfeld JW. Emergentuse of balloon-expandable coronary artery stenting for failed percutaneoustransluminal coronary angioplasty. Circulahm 1992;86:812-819. 10. Hall P, Nakamura S, Maiello L, Itob A, Blengino S, Martini G, Ferraro M, Colombo A. A randomized comoarison of combined ticlooidine and asoirin therapy versus aspirin therapy alone after successful intravascular ultrasdundguided stent implantation. Circulation 1996;93:215-222.
NOVEMBER 1, 1996