- Email: [email protected]
Effectiveness of tirofiban for failed thrombolysis during acute myocardial infarction
Effectiveness of Tirofiban for Failed Thrombolysis During Acute Myocardial Infarction Alfredo Vetrano, MD, Raffaele Carotenuto, MD, Fabrizio Corsini, MD, Margherita Schioppa, MD, Angela Martone, MD, Saverio Melorio, MD, Francesca Sideri, MD, Salvatore Romano, MD, Carmelo Chieffo, MD, and Giancarlo Corsini, MD The clinical outcome of 48 consective patients with myocardial infarction who received tirofiban for unsuccessful thrombolysis was compared with that of 48 patients matched for age, gender, and infarct location who did not receive rescue treatment. Those who received tirofiban had more successful reperfusions, and there were few bleeding complications. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;93:914 –916)
lycoprotein IIb/IIIa inhibitors have been recently proposed as a bridge to rescue percutaneous G transluminal coronary angioplasty in patients with STelevation myocardial infarction in whom thrombolysis fails, but data on their feasibility are still limited. In 48 consecutive patients with acute myocardial infarction in whom thrombolysis failed to achieve 90-minute reperfusion, tirofiban was given at a full dose. Our preliminary data suggest this approach is feasible, safe, and of clinical benefit in this high-risk subgroup of patients. •••
Between December 2001 and February 2003, 205 consecutive patients presenting with ST elevation ⬎1 mm in 2 consecutive limb leads or ⬎2 mm in 2 precordial leads, and with onset of symptoms occurring in ⬍6 hours without contraindications to thrombolytic treatment, were treated with accelerated fulldose alteplase. Adjunctive therapy included nitrates, heparin, and aspirin. Electrocardiograms were obtained before and 90 minutes after the start of thrombolytic therapy. Unsuccessful thrombolysis was defined as the recurrence or persistence of chest pain and intermittent or stable ST-segment elevation or a percent reduction of ⬍50% of the ⌺ ST elevation on a 12-lead electrocardiogram. Forty-eight patients who met the criteria for failed thrombolysis according to 2 independent physicians underwent tirofiban administration (bolus dose of 10 g/kg followed by an infusion of 0.15 g/kg/min for 48 hours). Unfractionated heparin was continued according to a prothrombin time of between 50 and 70 seconds. All enrolled patients underwent clinical monitoring for 30 days after the index acute event. From the Department of Cardiology, ICCU, Azienda Ospedaliera “San Sebastiano,” Caserta, Italy. Dr. Vetrano’s address is: Divisione di Cardiologia, Azienda Ospedaliera San Sebastiano, Via Tescione, traversa Palasciano, 81100 Caserta, Italy. E-mail: alfredovetrano@ virgilio.it. Manuscript received June 27, 2003; revised manuscript received and accepted December 8, 2003.
914
©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 93 April 1, 2004
Major cardiac events included death, reinfarction, congestive heart failure, urgent revascularization, and recurrent ischemia. Cardiac death was considered death due to cardiac causes. Reinfarction was defined as the occurrence of new, significant Q waves in 2 contiguous leads, and reelevation of creatine kinase-MB or troponin I. Congestive heart failure was defined as New York Heart Association class III to IV symptoms at the follow-up visit. Recurrent ischemia was defined as ischemic chest pain at rest associated with ischemic electrocardiographic changes. Major bleeding was defined as intracerebral bleeding, a decrease in hemoglobin of ⬎3.1 g/dl, or bleeding for which surgery was performed. Moderate bleeding was defined by the need for transfusion, and minor bleeding was defined as bleeding that did not require transfusion or cause hemodynamic compromise. Descriptive statistics include mean values and range or median values and 25th and 75th percentiles as appropriate. Categorical data are presented as absolute values and percentages. Normally distributed variables were compared using the unpaired t test. Prevalences were compared using Fisher’s exact test. Confidence intervals for proportions are also given. Clinical characteristics of the study patients are listed in Table 1. Tirofiban infusion began at 120 minutes (range 60 to 180) after the end of thrombolysis, with ⬎50% of the patients starting therapy with tirofiban by 80 minutes. One hundred twenty minutes after the beginning of tirofiban infusion, an electrocardiogram was obtained in all patients, revealing ST-segment elevation resolution in 15 patients (32%). After 240 minutes (range 180 to 300) 20 additional patients (42%) had normalization of ST segments on electrocardiography, whereas 12 (26%) had a reduction of ⌺ ST elevation of ⬎50%. All these patients had resolution of chest pain (90%). Between days 2 and 3, 4 patients (8%) underwent urgent percutaneous revascularization because of recurrent refractory postinfarction angina. During hospitalization, there were no deaths and 1 patient had myocardial reinfarction (2%). Of the 4 patients (8%) who presented with congestive heart failure at the beginning of treatment, 3 recovered within a few hours and 1 recovered after 12-hour treatment with intra-aortic balloon pump and inotropes. All patients were alive at the 30-day followup. One patient developed thrombocytopenia with major bleeding (retroperitoneal hematoma) and underwent transfusion, 1 patient had major bleeding (melena), and 1 patient’s bleeding was minor (gingi0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2003.12.035
unselected control group. Various rescue therapies have been considered in this setting and, in particular, Controls rescue percutaneous coronary inter(n ⫽ 48) vention2,3 and rescue lysis.4,5 Early 60 ⫾ 11 percutaneous intervention after clin37 (77%) ically unsuccessful thrombolysis is 22 (45%) successful in 90% of cases but with a 25 (52%) high risk of reocclusion (up to 30%), 11 (23%) 6 (13%) and if unsuccessful, a high mortality 30 (64%) rate.2,3,6 In addition, this mechanical 155 (41–360) therapy is of limited availability. 44/52/4% Given the importance of the platelet 102 (55–144) component of the thrombus in ex5 plaining thrombus resistance to lysis, 4 rescue therapy with glycoprotein IIb/ 12 IIIa receptor blockers in patients in 27 whom thrombolysis has failed may 45 (94%) be an attractive strategy.7 Few stud40 (83%) ies have assessed the effectiveness of 115 (50–155) glycoprotein IIb/IIIa inhibitors for rescue percutaneous transluminal 88 (0–105) coronary angioplasty. In the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries III (GUSTO-III) trial, a subset analysis of 387 patients with acute myocardial infarction who underwent rescue percutaneous transluminal coronary angioplasty after failed fibrinolytic therapy had a mortality rate at 30 days of 3.7% in 81 patients who received periprocedural abciximab, compared with a rate of 9.8% in the 306 patients who did not receive abciximab at a cost of an increased incidence of severe bleeding.8 A higher bleeding rate in patients receiving glycoprotein IIb/IIIa as an adjunct to rescue therapies for failed thrombolysis was observed in a retrospective study,9 but not in a small, prospective randomized trial.10 However, little is known about the feasibility and safety of glycoprotein IIb/IIIa use over thrombolysis in patients not undergoing immediate rescue revascularization. Preliminary data suggest a substantial clinical benefit, with an acceptable bleeding risk.10,11 Our data agree with this finding. However, the definition of refractory ischemia was not the rule in this study, but rather was left to the discretion of physicians. Therefore, the effect of tirofiban infusion, especially on this subjective end point, should be considered with caution. In our study group, the administration of tirofiban was associated with an overall ST-segment elevation resolution at 240 minutes in 75% of patients, with a good clinical outcome both during hospitalization and up to 30-day follow-up. The early normalization of ST segments and the disappearance of chest pain reflect the adequate reperfusion obtained from dissolution of the platelet components. Furthermore, the reduction in clinical events reflects that, as in experimental data, glycoprotein IIb/IIIa receptor inhibition leads to a more stable residual thrombus and avoids cyclic flow variations and repeat thrombosis.12,13 In our unselected series, bleeding events were infrequent and no major intracranial hemorrhages were observed.
TABLE 1 Demographic and Clinical Characteristics of the Study and Control Groups Study Group (n ⫽ 48)
Characteristics Age (mean ⫾ SD) (yrs) Men Hypertension Smokers Diabetes mellitus Previous acute myocardial infarction Hypercholesterolemia Time from index event (min) (mean) Site of infarction (anterior/inferior/lateral) Heart rate at arrival (beats/min) (range) Killip class IV III II I Incomplete 90-min ST resolution after thrombolytic therapy Persistence of symptoms after thrombolytic therapy Mean systolic blood pressure after thrombolysis (mm Hg) (range) Diastolic blood pressure (mm Hg) (range)
61 ⫾ 12 40 (83%) 28 (60%) 25 (53%) 14 (30%) 7 (15%) 30 (64%) 190 (35–360⬘) 47/45/8% 92 (66–122) 3 4 11 28 39 (85%) 32 (69%) 128 (60–165) 77 (0–100)
TABLE 2 Major Events During Hospitalization in the Two Groups Patients Receiving Rescue Tirofiban Controls p Value Death Death from periprocedural complications Refractory ischemia requiring urgent percutaneous coronary intervention Myocardial reinfarction Congestive heart failure Bleeding events
0 0
9 (19%) 4 (8%)
0.03 0.07
4 (8%)
17 (36%)
0.008
1 (0.5%) 4 (8%) 3 (6%)
8 (17%) 12 (25%) 0
0.02 0.05 0.1
val). The control group consisted of 48 consecutive patients with acute myocardial infarction admitted within 6 hours from symptom onset to our hospital between January 1999 and January 2000; the period at which tirofiban and rescue percutaneous transluminal coronary angioplasty were not available at our center. All patients received the same adjunctive therapy as the study group patients. Table 1 lists their clinical characteristics, which did not differ from the study population. After 120 minutes (the end of thrombolysis), no patient had resolution of ST-segment elevation. During hospitalization 9 patients died (19%), 8 (17%) had reinfarction, 12 (25%) had congestive heart failure, 17 (37%) underwent urgent procedures in other hospitals, and 4 of them (8%) died of periprocedural complications. No bleeding were observed in the control group. All these events were significantly higher than those in the study population (Table 2). •••
Mortality rates are very high when thrombolysis fails.1 This was confirmed by the high event rate in our
BRIEF REPORTS
915
The low incidence of bleeding in our study may be the result of a later tirofiban infusion; infusion was begun ⬎1 hour after the end of the thrombolytic drug, reducing the synergic prohemorrhagic effect of the 2 drugs when used simultaneously. Our uncontrolled data should be regarded as preliminary and highlight the need for randomized clinical trials in this field. 1. Califf RM, Topol EJ, George BS, Boswick JM, Lee KL, Stump D, Dillon J,
Abbottsmith C, Candela RJ, Kereiakes DJ. Characteristics and outcome of patients in whom reperfusion with intravenous tissue-type plasminogen activator fails: results of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I trial. Circulation 1988;77:1090 –1099. 2. The CORAMI Study Group. Outcome of attempted rescue coronary angioplasty after failed thrombolysis for acute myocardial infarction. Cohort of Rescue Angioplasty in Myocardial Infarction. J Am Coll Cardiol 1994;74:172–174. 3. Baim DS, Diver DJ, Knatterud GL, and the TIMI 2A Investigators. Percutaneous transluminal coronary angioplasty salvage for thrombolytic failures: implications from the TIMI 2A (abstr). Circulation 1988;78:II-112. 4. Barbash GI, Hod H, Rath S, Miller HI, Roth A, Har-Zahav Y, Modan M, Rotstein Z, Batler A, Zivelin A. Intermittent, dose-related fluctuations of pain and ST elevation during infusion of recombinant tissue plasminogen activator during acute myocardial infarction. J Am Coll Cardiol 1989;64:225–228. 5. White HD, Cross DB, Williams BF, Norris RM, Woo KS, Hamer AW, Elliott JM, Ormiston JA. Rescue thrombolysis with intracoronary tissue plasminogen activator for failed intravenous thrombolysis with streptokinase for acute myocardial infarction. J Am Coll Cardiol 1995;75:172–174.
6. Ellis SG, da Silva ER, Heyndrickx G, Talley JD, Cernigliaro C, Steg G,
Spaulding C, Nobuyoshi M, Erbel R, Vassanelli C, for the RESCUE Investigators. Randomized comparison of rescue angioplasty with conservative management of patients with early failure of thrombolysis for acute myocardial infarction. Circulation 1994;90:2280 –2284. 7. Muhlestein JB, Gomez MA, Karagounis LA, Anderson L. “Rescue Reopro”: acute utilization of abciximab for the dissolution of coronary thrombus developing as a complication of coronary angioplasty (abstr). Circulation 1995;92-607. 8. Miller JM, Smalling R, Ohman EM, Bode C, Betriu A, Kleiman NS, Schildcrout JS, Bastos E, Topol EJ, Califf RM. Effectiveness of early coronary angioplasty and abciximab for failed thrombolysis (reteplase or alteplase) during acute myocardial infarction. Results from the GUSTO-III trial. J Am Coll Cardiol 1999;84:779 –784. 9. Ronner E, van Domburg RT, van den Brand MJ, de Feyter PJ, Foley DP, van der Giessen WJ, Serruys PW, Simoons ML. Platelet glycoprotein IIb/IIIa receptor blockers for failed thrombolysis in acute myocardial infarction, alone or as adjunct to other rescue therapies. Eur Heart J 2002;23:1529 –1537. 10. Petronio AS, Musumeci G, Limbruno U, De Carlo M, Baglini R, Paterni G, Grazia Delle Donne M, Caravelli P, Nardi C, Mariani M. Abciximab improves 6-month clinical outcome after rescue coronary angioplasty. Am Heart J 2002; 143:334 –341. 11. Di Pasquale P, Sarullo FM, Cannizzaro S, Vitrano MG, Vincenzo B, Giambanco F, Scandurra A, Calcaterra G, Paterna S. Effect of administration of glycoprotein IIb/IIIa receptor antagonists in patients with failed thrombolysis. A pilot study. Clin Drug Invest 2001;21:545–553. 12. Jang IK, Gold HK, Ziskind AA, Fallon JT, Holt RE, Leinbach RC, May JW, Collen D. Differential sensivity of erythrocyte-rich and platelet-rich arterial thrombi to lysis with recombinant tissue-type plasminogen activator. Circulation 1989;79:920 –928. 13. Cigarroa JE, Ferrel MA, Collen DJ, Leinbach RC. Enhanced endogenous coronary thrombolysis during acute myocardial infarction following selective platelet receptor blockade with Reopro (abstr). Circulation 1996;94:I-553.
Comparison of Differences in Outcome After Percutaneous Coronary Intervention in Men Versus Women <40 Years of Age Alexandra J. Lansky, MD, Roxana Mehran, MD, George Dangas, MD, Ecaterina Cristea, MD, Kazuyuki Shirai, MD, Ricardo Costa, MD, Costantino Costantini, MD, Yoshihiro Tsuchiya, MD, Stephane Carlier, MD, Gary Mintz, MD, Yves Cottin, MD, PhD, Gregg Stone, MD, Jeffrey Moses, MD, and Martin B. Leon, MD We evaluated the outcomes of 177 consecutive patients (43 women, 134 men) <40 years of age with premature atherosclerosis who underwent percutaneous coronary intervention. Women were younger, had more diabetes mellitus (37% vs 10%; p <0.001), but less hyperlipidemia (58% vs 75%; p <0.001) compared with men. In-hospital vascular complications and 1-year mortality rate or Q-wave myocardial infarction (7.9% vs 0.08%, p <0.01) were higher in women. By multivariable regression analysis, female gender was the only independent predictor of vascular complications (odds ratio, 14.1; 95% confidence intervals, 1.59 to 125, p ⴝ 0.01) and of 1-year mortality rate or nonfatal myocardial infarction (odds ratio, 12.5; 95% confidence interval, 1.14 to 111, p From the Cardiovascular Research Foundation and the Lenox Hill Heart and Vascular Institute, New York, New York. Dr. Lansky’s address is: Cardiovascular Research Foundation, 55 East 59th Street, 6th Floor, New York, New York 10022. E-mail: [email protected]. Manuscript received September 26, 2003; revised manuscript received and accepted December 15, 2003.
916
©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 93 April 1, 2004
ⴝ 0.03). Women with premature coronary disease had a distinctive risk factor profile relative to men, with a predominance of diabetes and hypercholesterolemia, and were at higher risk of developing vascular and ischemic complications after percutaneous coronary intervention, warranting aggressive risk factor modification and vigilance in this population. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;93:916 –919)
he increasing incidence of cardiovascular disease and the associated mortality burden in United T States women has been attributed in large part to the growing population of older postmenopausal women.1 After percutaneous coronary intervention (PCI), the higher complication rates in women have been attributed largely to advanced age and other unfavorable clinical characteristics.2,3 For instance, after PCI, the hazard of death has been reported to increase by 65% with every 10-year increment in age.3 Although the prevalence of cardiovascular disease is low among young premenopausal women compared with age0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2003.12.046
lycoprotein IIb/IIIa inhibitors have been recently proposed as a bridge to rescue percutaneous G transluminal coronary angioplasty in patients with STelevation myocardial infarction in whom thrombolysis fails, but data on their feasibility are still limited. In 48 consecutive patients with acute myocardial infarction in whom thrombolysis failed to achieve 90-minute reperfusion, tirofiban was given at a full dose. Our preliminary data suggest this approach is feasible, safe, and of clinical benefit in this high-risk subgroup of patients. •••
Between December 2001 and February 2003, 205 consecutive patients presenting with ST elevation ⬎1 mm in 2 consecutive limb leads or ⬎2 mm in 2 precordial leads, and with onset of symptoms occurring in ⬍6 hours without contraindications to thrombolytic treatment, were treated with accelerated fulldose alteplase. Adjunctive therapy included nitrates, heparin, and aspirin. Electrocardiograms were obtained before and 90 minutes after the start of thrombolytic therapy. Unsuccessful thrombolysis was defined as the recurrence or persistence of chest pain and intermittent or stable ST-segment elevation or a percent reduction of ⬍50% of the ⌺ ST elevation on a 12-lead electrocardiogram. Forty-eight patients who met the criteria for failed thrombolysis according to 2 independent physicians underwent tirofiban administration (bolus dose of 10 g/kg followed by an infusion of 0.15 g/kg/min for 48 hours). Unfractionated heparin was continued according to a prothrombin time of between 50 and 70 seconds. All enrolled patients underwent clinical monitoring for 30 days after the index acute event. From the Department of Cardiology, ICCU, Azienda Ospedaliera “San Sebastiano,” Caserta, Italy. Dr. Vetrano’s address is: Divisione di Cardiologia, Azienda Ospedaliera San Sebastiano, Via Tescione, traversa Palasciano, 81100 Caserta, Italy. E-mail: alfredovetrano@ virgilio.it. Manuscript received June 27, 2003; revised manuscript received and accepted December 8, 2003.
914
©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 93 April 1, 2004
Major cardiac events included death, reinfarction, congestive heart failure, urgent revascularization, and recurrent ischemia. Cardiac death was considered death due to cardiac causes. Reinfarction was defined as the occurrence of new, significant Q waves in 2 contiguous leads, and reelevation of creatine kinase-MB or troponin I. Congestive heart failure was defined as New York Heart Association class III to IV symptoms at the follow-up visit. Recurrent ischemia was defined as ischemic chest pain at rest associated with ischemic electrocardiographic changes. Major bleeding was defined as intracerebral bleeding, a decrease in hemoglobin of ⬎3.1 g/dl, or bleeding for which surgery was performed. Moderate bleeding was defined by the need for transfusion, and minor bleeding was defined as bleeding that did not require transfusion or cause hemodynamic compromise. Descriptive statistics include mean values and range or median values and 25th and 75th percentiles as appropriate. Categorical data are presented as absolute values and percentages. Normally distributed variables were compared using the unpaired t test. Prevalences were compared using Fisher’s exact test. Confidence intervals for proportions are also given. Clinical characteristics of the study patients are listed in Table 1. Tirofiban infusion began at 120 minutes (range 60 to 180) after the end of thrombolysis, with ⬎50% of the patients starting therapy with tirofiban by 80 minutes. One hundred twenty minutes after the beginning of tirofiban infusion, an electrocardiogram was obtained in all patients, revealing ST-segment elevation resolution in 15 patients (32%). After 240 minutes (range 180 to 300) 20 additional patients (42%) had normalization of ST segments on electrocardiography, whereas 12 (26%) had a reduction of ⌺ ST elevation of ⬎50%. All these patients had resolution of chest pain (90%). Between days 2 and 3, 4 patients (8%) underwent urgent percutaneous revascularization because of recurrent refractory postinfarction angina. During hospitalization, there were no deaths and 1 patient had myocardial reinfarction (2%). Of the 4 patients (8%) who presented with congestive heart failure at the beginning of treatment, 3 recovered within a few hours and 1 recovered after 12-hour treatment with intra-aortic balloon pump and inotropes. All patients were alive at the 30-day followup. One patient developed thrombocytopenia with major bleeding (retroperitoneal hematoma) and underwent transfusion, 1 patient had major bleeding (melena), and 1 patient’s bleeding was minor (gingi0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2003.12.035
unselected control group. Various rescue therapies have been considered in this setting and, in particular, Controls rescue percutaneous coronary inter(n ⫽ 48) vention2,3 and rescue lysis.4,5 Early 60 ⫾ 11 percutaneous intervention after clin37 (77%) ically unsuccessful thrombolysis is 22 (45%) successful in 90% of cases but with a 25 (52%) high risk of reocclusion (up to 30%), 11 (23%) 6 (13%) and if unsuccessful, a high mortality 30 (64%) rate.2,3,6 In addition, this mechanical 155 (41–360) therapy is of limited availability. 44/52/4% Given the importance of the platelet 102 (55–144) component of the thrombus in ex5 plaining thrombus resistance to lysis, 4 rescue therapy with glycoprotein IIb/ 12 IIIa receptor blockers in patients in 27 whom thrombolysis has failed may 45 (94%) be an attractive strategy.7 Few stud40 (83%) ies have assessed the effectiveness of 115 (50–155) glycoprotein IIb/IIIa inhibitors for rescue percutaneous transluminal 88 (0–105) coronary angioplasty. In the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries III (GUSTO-III) trial, a subset analysis of 387 patients with acute myocardial infarction who underwent rescue percutaneous transluminal coronary angioplasty after failed fibrinolytic therapy had a mortality rate at 30 days of 3.7% in 81 patients who received periprocedural abciximab, compared with a rate of 9.8% in the 306 patients who did not receive abciximab at a cost of an increased incidence of severe bleeding.8 A higher bleeding rate in patients receiving glycoprotein IIb/IIIa as an adjunct to rescue therapies for failed thrombolysis was observed in a retrospective study,9 but not in a small, prospective randomized trial.10 However, little is known about the feasibility and safety of glycoprotein IIb/IIIa use over thrombolysis in patients not undergoing immediate rescue revascularization. Preliminary data suggest a substantial clinical benefit, with an acceptable bleeding risk.10,11 Our data agree with this finding. However, the definition of refractory ischemia was not the rule in this study, but rather was left to the discretion of physicians. Therefore, the effect of tirofiban infusion, especially on this subjective end point, should be considered with caution. In our study group, the administration of tirofiban was associated with an overall ST-segment elevation resolution at 240 minutes in 75% of patients, with a good clinical outcome both during hospitalization and up to 30-day follow-up. The early normalization of ST segments and the disappearance of chest pain reflect the adequate reperfusion obtained from dissolution of the platelet components. Furthermore, the reduction in clinical events reflects that, as in experimental data, glycoprotein IIb/IIIa receptor inhibition leads to a more stable residual thrombus and avoids cyclic flow variations and repeat thrombosis.12,13 In our unselected series, bleeding events were infrequent and no major intracranial hemorrhages were observed.
TABLE 1 Demographic and Clinical Characteristics of the Study and Control Groups Study Group (n ⫽ 48)
Characteristics Age (mean ⫾ SD) (yrs) Men Hypertension Smokers Diabetes mellitus Previous acute myocardial infarction Hypercholesterolemia Time from index event (min) (mean) Site of infarction (anterior/inferior/lateral) Heart rate at arrival (beats/min) (range) Killip class IV III II I Incomplete 90-min ST resolution after thrombolytic therapy Persistence of symptoms after thrombolytic therapy Mean systolic blood pressure after thrombolysis (mm Hg) (range) Diastolic blood pressure (mm Hg) (range)
61 ⫾ 12 40 (83%) 28 (60%) 25 (53%) 14 (30%) 7 (15%) 30 (64%) 190 (35–360⬘) 47/45/8% 92 (66–122) 3 4 11 28 39 (85%) 32 (69%) 128 (60–165) 77 (0–100)
TABLE 2 Major Events During Hospitalization in the Two Groups Patients Receiving Rescue Tirofiban Controls p Value Death Death from periprocedural complications Refractory ischemia requiring urgent percutaneous coronary intervention Myocardial reinfarction Congestive heart failure Bleeding events
0 0
9 (19%) 4 (8%)
0.03 0.07
4 (8%)
17 (36%)
0.008
1 (0.5%) 4 (8%) 3 (6%)
8 (17%) 12 (25%) 0
0.02 0.05 0.1
val). The control group consisted of 48 consecutive patients with acute myocardial infarction admitted within 6 hours from symptom onset to our hospital between January 1999 and January 2000; the period at which tirofiban and rescue percutaneous transluminal coronary angioplasty were not available at our center. All patients received the same adjunctive therapy as the study group patients. Table 1 lists their clinical characteristics, which did not differ from the study population. After 120 minutes (the end of thrombolysis), no patient had resolution of ST-segment elevation. During hospitalization 9 patients died (19%), 8 (17%) had reinfarction, 12 (25%) had congestive heart failure, 17 (37%) underwent urgent procedures in other hospitals, and 4 of them (8%) died of periprocedural complications. No bleeding were observed in the control group. All these events were significantly higher than those in the study population (Table 2). •••
Mortality rates are very high when thrombolysis fails.1 This was confirmed by the high event rate in our
BRIEF REPORTS
915
The low incidence of bleeding in our study may be the result of a later tirofiban infusion; infusion was begun ⬎1 hour after the end of the thrombolytic drug, reducing the synergic prohemorrhagic effect of the 2 drugs when used simultaneously. Our uncontrolled data should be regarded as preliminary and highlight the need for randomized clinical trials in this field. 1. Califf RM, Topol EJ, George BS, Boswick JM, Lee KL, Stump D, Dillon J,
Abbottsmith C, Candela RJ, Kereiakes DJ. Characteristics and outcome of patients in whom reperfusion with intravenous tissue-type plasminogen activator fails: results of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I trial. Circulation 1988;77:1090 –1099. 2. The CORAMI Study Group. Outcome of attempted rescue coronary angioplasty after failed thrombolysis for acute myocardial infarction. Cohort of Rescue Angioplasty in Myocardial Infarction. J Am Coll Cardiol 1994;74:172–174. 3. Baim DS, Diver DJ, Knatterud GL, and the TIMI 2A Investigators. Percutaneous transluminal coronary angioplasty salvage for thrombolytic failures: implications from the TIMI 2A (abstr). Circulation 1988;78:II-112. 4. Barbash GI, Hod H, Rath S, Miller HI, Roth A, Har-Zahav Y, Modan M, Rotstein Z, Batler A, Zivelin A. Intermittent, dose-related fluctuations of pain and ST elevation during infusion of recombinant tissue plasminogen activator during acute myocardial infarction. J Am Coll Cardiol 1989;64:225–228. 5. White HD, Cross DB, Williams BF, Norris RM, Woo KS, Hamer AW, Elliott JM, Ormiston JA. Rescue thrombolysis with intracoronary tissue plasminogen activator for failed intravenous thrombolysis with streptokinase for acute myocardial infarction. J Am Coll Cardiol 1995;75:172–174.
6. Ellis SG, da Silva ER, Heyndrickx G, Talley JD, Cernigliaro C, Steg G,
Spaulding C, Nobuyoshi M, Erbel R, Vassanelli C, for the RESCUE Investigators. Randomized comparison of rescue angioplasty with conservative management of patients with early failure of thrombolysis for acute myocardial infarction. Circulation 1994;90:2280 –2284. 7. Muhlestein JB, Gomez MA, Karagounis LA, Anderson L. “Rescue Reopro”: acute utilization of abciximab for the dissolution of coronary thrombus developing as a complication of coronary angioplasty (abstr). Circulation 1995;92-607. 8. Miller JM, Smalling R, Ohman EM, Bode C, Betriu A, Kleiman NS, Schildcrout JS, Bastos E, Topol EJ, Califf RM. Effectiveness of early coronary angioplasty and abciximab for failed thrombolysis (reteplase or alteplase) during acute myocardial infarction. Results from the GUSTO-III trial. J Am Coll Cardiol 1999;84:779 –784. 9. Ronner E, van Domburg RT, van den Brand MJ, de Feyter PJ, Foley DP, van der Giessen WJ, Serruys PW, Simoons ML. Platelet glycoprotein IIb/IIIa receptor blockers for failed thrombolysis in acute myocardial infarction, alone or as adjunct to other rescue therapies. Eur Heart J 2002;23:1529 –1537. 10. Petronio AS, Musumeci G, Limbruno U, De Carlo M, Baglini R, Paterni G, Grazia Delle Donne M, Caravelli P, Nardi C, Mariani M. Abciximab improves 6-month clinical outcome after rescue coronary angioplasty. Am Heart J 2002; 143:334 –341. 11. Di Pasquale P, Sarullo FM, Cannizzaro S, Vitrano MG, Vincenzo B, Giambanco F, Scandurra A, Calcaterra G, Paterna S. Effect of administration of glycoprotein IIb/IIIa receptor antagonists in patients with failed thrombolysis. A pilot study. Clin Drug Invest 2001;21:545–553. 12. Jang IK, Gold HK, Ziskind AA, Fallon JT, Holt RE, Leinbach RC, May JW, Collen D. Differential sensivity of erythrocyte-rich and platelet-rich arterial thrombi to lysis with recombinant tissue-type plasminogen activator. Circulation 1989;79:920 –928. 13. Cigarroa JE, Ferrel MA, Collen DJ, Leinbach RC. Enhanced endogenous coronary thrombolysis during acute myocardial infarction following selective platelet receptor blockade with Reopro (abstr). Circulation 1996;94:I-553.
Comparison of Differences in Outcome After Percutaneous Coronary Intervention in Men Versus Women <40 Years of Age Alexandra J. Lansky, MD, Roxana Mehran, MD, George Dangas, MD, Ecaterina Cristea, MD, Kazuyuki Shirai, MD, Ricardo Costa, MD, Costantino Costantini, MD, Yoshihiro Tsuchiya, MD, Stephane Carlier, MD, Gary Mintz, MD, Yves Cottin, MD, PhD, Gregg Stone, MD, Jeffrey Moses, MD, and Martin B. Leon, MD We evaluated the outcomes of 177 consecutive patients (43 women, 134 men) <40 years of age with premature atherosclerosis who underwent percutaneous coronary intervention. Women were younger, had more diabetes mellitus (37% vs 10%; p <0.001), but less hyperlipidemia (58% vs 75%; p <0.001) compared with men. In-hospital vascular complications and 1-year mortality rate or Q-wave myocardial infarction (7.9% vs 0.08%, p <0.01) were higher in women. By multivariable regression analysis, female gender was the only independent predictor of vascular complications (odds ratio, 14.1; 95% confidence intervals, 1.59 to 125, p ⴝ 0.01) and of 1-year mortality rate or nonfatal myocardial infarction (odds ratio, 12.5; 95% confidence interval, 1.14 to 111, p From the Cardiovascular Research Foundation and the Lenox Hill Heart and Vascular Institute, New York, New York. Dr. Lansky’s address is: Cardiovascular Research Foundation, 55 East 59th Street, 6th Floor, New York, New York 10022. E-mail: [email protected]. Manuscript received September 26, 2003; revised manuscript received and accepted December 15, 2003.
916
©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 93 April 1, 2004
ⴝ 0.03). Women with premature coronary disease had a distinctive risk factor profile relative to men, with a predominance of diabetes and hypercholesterolemia, and were at higher risk of developing vascular and ischemic complications after percutaneous coronary intervention, warranting aggressive risk factor modification and vigilance in this population. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;93:916 –919)
he increasing incidence of cardiovascular disease and the associated mortality burden in United T States women has been attributed in large part to the growing population of older postmenopausal women.1 After percutaneous coronary intervention (PCI), the higher complication rates in women have been attributed largely to advanced age and other unfavorable clinical characteristics.2,3 For instance, after PCI, the hazard of death has been reported to increase by 65% with every 10-year increment in age.3 Although the prevalence of cardiovascular disease is low among young premenopausal women compared with age0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2003.12.046