- Email: [email protected]
Comparison of results of coronary angioplasty for acute myocardial infarction in patients ≥75 years of age versus patients <75 years of age
Comparison of Results of Coronary Angioplasty for Acute Myocardial Infarction in Patients >75 Years of Age Versus Patients <75 Years of Age Koyu Sakai, MD, Yoshihisa Nakagawa, MD, Takeshi Kimura, MD, Takahiro Doi, Hiroyoshi Yokoi, MD, Masashi Iwabuchi, MD, Naoya Hamasaki, MD, Katsumi Inoue, MD, Hideyuki Nosaka, MD, and Masakiyo Nobuyoshi, MD
MD,
We reviewed 1,063 consecutive patients treated with direct coronary angioplasty for acute myocardial infarction (AMI): 261 were >75 and 802 were <75 years of age. Compared with the younger group, the older group had a higher percentage of women (48% vs 22%, p <0.0001), multivessel coronary disease (50% vs 39%, p <0.01), overall in-hospital mortality (8.4% vs 3.7%, p <0.01), cardiac mortality rate (6.1% vs 3.1%, p <0.05), and noncardiac mortality rate (2.3% vs 0.6%, p <0.05). Successful reperfusion was achieved in both groups at a
similarly high rate (93% and 95%, p ⴝ NS). Hospital mortality was similar whether reperfusion was successful or failed. Successful compared with unsuccessful angioplasty decreased mortality rates in the older (6.6% vs 33%, p <0.0001) and younger (3.0% vs 18%, p <0.0001) groups. When reperfusion was successful, the cardiac mortality rate in older patients was not significantly higher than in younger patients: 4.1% vs 2.4%, p ⴝ NS. 䊚2002 by Excerpta Medica, Inc. (Am J Cardiol 2002;89:797– 800)
irect coronary angioplasty expands the reperfusion population to include many patients that D would be considered ineligible for thrombolysis be-
injected into the infarct-related artery to rule out possible coronary spasm involvement; 162 mg of chewable aspirin was given before angioplasty. The balloon was inflated 2 or 3 times for 60 seconds at a pressure ranging from 6 to 10 atm routinely. Adjunctive stent implantation was performed if (1) the residual diameter stenosis was ⱖ30%, (2) there was complex coronary dissection, and (3) the anatomy was suitable for stenting (adequate vessel size and suitable focal lesion). The stents were routinely deployed at a pressure ranging from 6 to 16 atm, and for angiographic optimization, adjunctive high-pressure balloon dilation was performed if necessary. After angioplasty, all patients were admitted to the coronary care unit where 500 IU/hour of intravenous heparin drip for at least 48 hours and 162 or 243 mg/day of oral aspirin were given; 200 mg/day ticlopidine was added in patients who had stents. Reperfusion was considered successful if residual lumen diameter stenosis was ⬍50% with Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow.11 Causes of mortality: In-hospital mortality was divided into cardiac and noncardiac mortality. In addition, causes of cardiac mortality were classified into cardiogenic shock (if hemodynamic state could not be restored), congestive heart failure (if the patient died with pulmonary edema, hepatomegaly, peripheral edema, pleural effusion, or ascites), myocardial rupture, and arrhythmia. Cardiogenic shock was defined as systolic blood pressure ⬍90 mm Hg, peripheral signs of vascular collapse, decreased urinary output, and disturbance of consciousness. Statistical analysis: Values are expressed as mean ⫾ SD. Categorical variables were analyzed by chisquare test. Serial paired numerical data were com-
cause of high risk of intracranial hemorrhage.1–10 This retrospective study compares the benefits of direct coronary angioplasty in patients aged ⱖ75 years with those in patients aged ⬍75 years during acute myocardial infarction (AMI).
METHODS
Patient population: All consecutive patients with AMI who underwent direct coronary angioplasty within 24 hours of onset of symptoms or beyond 24 hours if myocardial ischemic symptoms persisted, treated at Kokura Memorial Hospital between January 1994 and December 1998, were entered in this analysis. Patients met the following criteria: (1) ST-segment elevation or depression in the electrocardiogram consistent with AMI, (2) symptoms of myocardial ischemia lasting ⬎20 minutes, and (3) creatine kinase elevation to ⬎2 times the normal value. Patients were divided according to age into ⱖ75 and ⬍75, defined as older and younger patients. Direct coronary angioplasty: Emergency coronary angiography and angioplasty were performed by the percutaneous femoral approach. Heparin (10,000 U) was administered when arterial access was secured. After visualizing both the left and right coronary arteries, 2.5 mg of isosorbide dinitrate was selectively From Kokura Memorial Hospital, Kitakyushu, Japan. Manuscript received September 18, 2001; revised manuscript received and accepted December 20, 2001. Address for reprints: Masakiyo Nobuyoshi, MD, Kokura Memorial Hospital, 1-1 Kifune-machi, Kokurakita-ku, Kitakyushu, Japan 8028555. E-mail: [email protected]. ©2002 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 89 April 1, 2002
0002-9149/02/$–see front matter PII S0002-9149(02)02187-2
797
TABLE 1 Patient Characteristics and Outcomes Patients Characteristics Age (yrs) Women Systemic hypertension Diabetes mellitus Hyperlipidemia* Prior myocardial infarction Infarct-related artery Left anterior descending Right Left circumflex Left main Saphenous vein graft Multivessel coronary disease Time from onset of symptoms to angioplasty (h) Procedural outcomes Stenting Successful reperfusion In-hospital mortality and causes of death Overall mortality Cardiac mortality Cardiogenic shock Congestive heart failure Myocardial rupture Arrhythmia Noncardiac mortality
ⱖ75 yrs (n ⫽ 261)
⬍75 yrs (n ⫽ 802)
80.8 ⫾ 4.6 124 (47.5%) 137 (52.5%) 67 (25.7%) 22 (8.4%) 28 (10.7%)
61.2 ⫾ 9.3 180 (22.4%) 333 (41.5%) 201 (25.1%) 134 (16.7%) 98 (12.2%)
⬍0.0001 ⬍0.0001 ⬍0.01 NS ⬍0.01 NS
116 (44.4%) 117 (44.8%) 25 (9.6%) 2 (0.8%) 1 (0.4%) 131 (50.2%) 12.3 ⫾ 24.7
398 (49.6%) 267 (33.3%) 117 (14.6%) 12 (1.5%) 8 (1.0%) 314 (39.2%) 11.3 ⫾ 33.3
NS ⬍0.001 ⬍0.05 NS NS ⬍0.01 NS
105 (40.2%) 243 (93.1%)
332 (41.4%) 762 (95.0%)
22 16 8 4 2 2 6
(8.4%) (6.1%) (3.1%) (1.5%) (0.8%) (0.8%) (2.3%)
30 25 18 3 3 2 5
(3.7%) (3.1%) (2.2%) (0.4%) (0.4%) (0.2%) (0.6%)
p Value
NS NS ⬍0.01 ⬍0.05 NS ⬍0.05 NS NS ⬍0.05
*With therapy and/or total cholesterol level ⬎220 mg/dl or triglyceride level ⬎150 mg/dl.
less likely to have a history of hyperlipidemia (8.4% vs 16.7%, p ⬍0.01). The right coronary artery was the infarct-related artery significantly more often and the left circumflex artery was involved significantly less often in the older group. Multivessel coronary disease was significantly more prevalent in the older patients (50.2% vs 39.2%, p ⬍0.01).
Direct coronary angioplasty (Table 1): Stenting was required as fre-
quently in older as in younger patients (40.2% vs 41.4%, p ⫽ NS). Successful reperfusion was achieved in 243 older (93.1%) and in 762 younger (95.0%) patients. In-hospital mortality and causes of death (Table 1): Older patients had a
significantly higher incidence of cardiac (p ⬍0.05), noncardiac (p ⬍0.05), and overall mortality (p ⬍0.01) than younger patients. Among the cardiac deaths, only congestive heart failure had a significantly higher incidence in the older patients (p ⬍0.05).
Does successful reperfusion alter in-hospital mortality? (Figure 1): Suc-
cessful direct coronary angioplasty decreased the in-hospital mortality rate significantly in both groups (p ⬍0.0001).
Does successful reperfusion alter the nature of in-hospital mortality? (Figure 2): Sixteen of 243 older patients with
FIGURE 1. In-hospital mortality of patients with successful reperfusion compared with those with unsuccessful reperfusion in both groups.
pared by the paired t test, and other continuous variables by the unpaired t test. A p value ⬍0.05 was regarded as significant.
RESULTS
Patient characteristics (Table 1): There were some baseline differences: 47.5% of the older patients and 22.4% of the younger patients were women (p ⬍0.0001). Older patients were more likely to have a history of systemic hypertension (52.5% vs 41.5%, p ⬍0.01) and 798 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 89
successful reperfusion (6.6%) died in the hospital: 10 (4.1%) of cardiac and 6 (2.5%) of noncardiac causes. Of 762 younger patients with successful reperfusion, 23 (3.0%) died in the hospital: 18 (2.4%) were cardiac and 5 (0.7%) noncardiac deaths. Thus, older patients had a significantly higher incidence of noncardiac and overall mortality than younger patients (p ⬍0.05), but the cardiac mortality rate was as low in younger patients when successful reperfusion was achieved. Does reperfusion failure affect the nature of in-hospital mortality? (Figure 3): Of 18 older patients with unsuc-
cessful reperfusion, 6 (33.3%) died in the hospital of cardiac causes; none died of noncardiac causes. All 7 younger patients with unsuccessful reperfusion died in the hospital from cardiac causes; none died of noncardiac causes. Reperfusion failure caused cardiac inhospital death regardless of age.
DISCUSSION Our results suggest that direct angioplasty should be undertaken regardless of age. Although successAPRIL 1, 2002
mortality in older patients was not higher than that in younger patients, provided that successful reperfusion was achieved. Reperfusion by direct angioplasty decreases the cardiac mortality rate regardless of age and should be implemented more aggressively, even in older patients, especially in those who are not suited for thrombolytic therapy.1–3 Study limitations: This study has several important limitations: (1) the study period of our patients was from 1994 to 1998. Improvements in hospital logistics, new devices,16 –19 and new drugs20 FIGURE 2. In-hospital mortality of older patients with successful reperfusion comhave been introduced since then, and the pared with that of younger patients with successful reperfusion with regard to advantages of direct angioplasty may cardiac, noncardiac, and overall mortality. become even greater21; (2) these results were achieved in an experienced investigational single center, and may not be applicable to all institutions. The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) angiographic substudy22 demonstrated the important link between survival of patients undergoing reperfusion and early attainment of complete (TIMI grade 3 flow) infarct artery patency. The tissue plasminogen activator regimen used preceded the acceptance of front loading, and this may have had an impact on vessel patency and clinical outcome.23 However, even with frontloaded tissue plasminogen activator, the restoration of TIMI grade 3 flow is still well below that achieved with diFIGURE 3. In-hospital mortality of older patients with unsuccessful reperfusion comrect angioplasty.2,22–24 Although the pared with that of younger patients with unsuccessful reperfusion with regard to results of direct angioplasty are related cardiac, noncardiac, and overall mortality. to the experience of performing physicians,25 results similar to the Primary ful reperfusion can be achieved in a high proportion Angioplasty in Myocardial Infarction (PAMI-I) trial26 of older patients (ⱖ75 years of age) and can greatly and the Netherlands study27,28 are achievable in decrease the overall in-hospital mortality rate to smaller, less experienced units by ensuring efficient 8.4%,12–14 this rate is still more than twice that in triage and prompt intervention.29 younger patients. Cardiac mortality due to congestive heart failure Acknowledgment: We are indebted to Alfonso-T was significantly higher in older patients,4,5 suggest- Miyamoto, MD, for his help with the manuscript. ing that the proposed therapeutic strategy would indeed be most effective in decreasing the mortality rate. De Boer et al15 compared direct angioplasty with 1. Himbert D, Juliard JM, Steg PG, Badaoui G, Baleynaud S, Le Guludec D, thrombolysis; direct angioplasty resulted in a lower Aumont MC, Gourgon R. Primary coronary angioplasty for acute myocardial with contraindication to thrombolysis. Am J Cardiol 1993;71:377–381. incidence of in-hospital mortality (2% vs 7%, p infarction 2. Grines CL, Browne KF, Marco J, Rothbaum D, Stone GW, O’Keefe J, Overlie ⬍0.05) and better left ventricular function (predis- P, Donohue B, Chelliah N, Timmis GC, et al. A comparison of immediate charge ejection fraction, 50% vs 45%; p ⬍0.001) than angioplasty with thrombolytic therapy for acute myocardial infarction. The Primary Angioplasty in Myocardial Infarction Study Group. N Engl J Med 1993; thrombolysis. Direct angioplasty salvages more myo- 328:673–679. cardium than thrombolytic therapy, thus preventing 3. Weaver WD, Litwin PE, Martin JS, Kudenchuk PJ, Maynard C, Eisenberg MS, MT, Cobb LA, Kennedy JW, Wirkus MS. Effect of age on use of thrombodevelopment of congestive heart failure, effective par- Ho lytic therapy and mortality in acute myocardial infarction. The MITI Project ticularly in the older population. Group. J Am Coll Cardiol 1991;18:657–662. The results of the present study confirm that direct 4. Delvin W, Cragg D, Jacks M, Friedman H, O’Neill W, Grines C. Comparison outcome in patients with acute myocardial infarction aged ⬎75 years with that coronary angioplasty in older patients effectively re- of in younger patients. Am J Cardiol 1995;75:573–576. duced in-hospital mortality to the point that cardiac 5. Paul SD, O’Gara PT, Mahjoub ZA, DiSalvo TG, O’Donnell CJ, Newell JB, CORONARY ARTERY DISEASE/ANGIOPLASTY FOR AMI IN OLDER PATIENTS
799
Villarreal-Levy G, Smith AJ, Kondo NI, Cararach M, Ferrer L, Eagle KA. Geriatric patients with acute myocardial infarction: cardiac risk factor profiles, presentation, thrombolysis, coronary interventions, and prognosis. Am Heart J 1996;131:710 –715. 6. Lew AS, Hod H, Cercek B, Shah PK, Ganz W. Mortality and morbidity rates of patients older and younger than 75 years with acute myocardial infarction treated with intravenous streptokinase. Am J Cardiol 1987;59:1–5. 7. Thiemann DR, Coresh J, Schulman SP, Gerstenblith G, Oetgen WJ, Powe NR. Lack of benefit for intravenous thrombolysis in patients with myocardial infarction who are older than 75 years. Circulation 2000;101:2239 –2246. 8. O’Connor CM, Califf RM, Massey EW, Mark DB, Kereiakes DJ, Candela RJ, Abbottsmith C, George B, Stack RS, Aronson L, Mantell S, Topol EJ. Stroke and acute myocardial infarction in the thrombolytic era: clinical correlates and longterm prognosis. J Am Coll Cardiol 1990;16:533–540. 9. de Jaegere PP, Arnold AA, Balk AH, Simoons ML. Intracranial hemorrhage in association with thrombolytic therapy: incidence and clinical predictive factors. J Am Coll Cardiol 1992;19:289 –294. 10. Simoons ML, Maggioni AP, Knatterud G, Leimberger JD, de Jaegere P, van Domburg R, Boersma E, Franzosi MG, Califf R, Schroder R, Braunwald E. Individual risk assessment for intracranial hemorrage during thrombolytic therapy. Lancet 1993;342:1523–1528. 11. TIMI Study Group. The Thrombolysis In Myocardial Infarction (TIMI) trial. N Engl J Med 1985;312:932–936. 12. Lee TC, Laramee LA, Rutherford BD, McConahay DR, Johnson WR Jr, Giorgi LV, Ligon RW, Hartzler GO. Emergency percutaneous transluminal coronary angioplasty for acute myocardial infarction in patients 70 years of age and older. Am J Cardiol 1990;66:663–667. 13. Yabe Y, Muramatsu T, Nakano H, Wagatsuma K. Efficacy and issues of emergent percutaneous transluminal coronary angioplasty. Comparison of clinical results in younger and elderly patients. Angiology 1995;46:1085–1095. 14. Laster SB, Rutherford BD, Giorgi LV, Shimshak TM, McConahay DR, Johnson WL Jr, Huber KC, Ligon RW, Hartzler GO. Results of direct percutaneous transluminal coronary angioplasty in octogenarians. Am J Cardiol 1996; 77:10 –13. 15. de Boer MJ, Hoorntje JC, Ottervanger JP, Reiffers S, Suryapranata H, Zijlstra F. Immediate coronary angioplasty versus intravenous streptokinase in acute myocardial infarction: left ventricular ejection fraction, hospital mortality and reinfarction. J Am Coll Cardiol 1994;23:1004 –1008. 16. Stone GW, Brodie BR, Griffin JJ, Morice MC, Costantini C, St. Goar FG, Overlie PA, Popma JJ, McDonnell J, Jones D, O’Neill WW, Grines CL. A prospective, multicenter study of the safety and feasibility of primary stenting in acute myocardial infarction: in-hospital and 30 day results of the PAMI Stent Pilot Trial. J Am Coll Cardiol 1998;31:23–30. 17. Suryapranata H, van’t Hof AW, Hoorntje JC, de Boer MJ, Zijlstra F. Randomized comparison of coronary stenting with balloon angioplasty in selected patients with acute myocardial infarction. Circulation 1998;97:2502–2505. 18. Nakagawa Y, Matsuo S, Kimura T, Yokoi H, Tamura T, Hamasaki N, Nosaka H, Nobuyoshi M. Thrombectomy with AngioJet catheter in native coronary
800 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 89
arteries for patients with acute or recent myocardial infarction. Am J Cardiol 1999;83:994 –999. 19. Rosenschein U, Roth A, Rassin T, Basen S, Laniado S, Miller HI. Analysis of coronary ultrasound thrombolysis endpoints in acute myocardial infarction (ACUTE Trial). Circulation 1997;95:1411–1416. 20. Brener SJ, Barr LA, Burchenal JEB, Katz S, George BS, Jones AA, Cohen ED, Gainey PC, White HJ, Cheek HB, et al, on behalf of the ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators. Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. Circulation 1998;98:734 – 741. 21. Schomig A, Kastrati A, Dirschinger J, Mehilli J, Schricke U, Pache J, Martinoff S, Neumann FJ, Schwaiger M. Coronary stenting plus platelet glycoprotein IIb/IIIa blockade compared with tissue plasminogen activator in acute myocardial infarction. N Engl J Med 2000;343:385–391. 22. The GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 1993;329:1615– 1622. 23. The GUSTO Investigators. An intertnational randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329: 673–682. 24. The Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) Angioplasty Substudy Investigators. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. N Engl J Med 1997;336:1621–1628. 25. Grassman ED, Johnson SA, Krone RJ. Predictors of success and major complications for percutaneous transluminal coronary angioplasty in acute myocardial infarction. An analysis of the 1990 to 1994 Society for Cardiac Angiography and Interventions Registries. J Am Coll Cardiol 1997;30:201–208. 26. Nunn CM, O’Neill WW, Rothbaum D, Stone GW, O’Keefe J, Overlie P, Donohue B, Grines L, Browne KF, Vlietstra RE, Catlin T, Grines CL, for The Primary Angioplasty in Myocardial Infarction I Study Group. Long-term outcome after primary angioplasty: report from the primary angioplasty in myocardial infarction (PAMI-I) trial. J Am Coll Cardiol 1999;33:640 –646. 27. Zijlstra F, de Boer MJ, Hoorntje JC, Reiffers S, Reiber JH, Suryapranata H. A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N Engl J Med 1993;328:680 –684. 28. Zijlstra F, Hoorntje JC, de Boer MJ, Reiffers S, Miedema K, Ottervanger JP, van’T Hof AW, Suryapranata H. Long-term benefit of primary angioplasty as compared with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1999;341:1413–1419. 29. Zahn R, Schiele R, Schneider S, Gitt AK, Wienbergen H, Siedl K, Bossalleer C, Buttner HJ, Gottwik M, Altmann E, Rosahl W, Senges J, for the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA), and the Myocardial Infarction Registry (MIR) Study Groups. Decreasing hospital mortality between 1994 and 1998 in patients with primary angioplasty but not in patients treated with intravenous thrombolysis. J Am Coll Cardiol 2000;36:2064 –2071.
APRIL 1, 2002
MD,
We reviewed 1,063 consecutive patients treated with direct coronary angioplasty for acute myocardial infarction (AMI): 261 were >75 and 802 were <75 years of age. Compared with the younger group, the older group had a higher percentage of women (48% vs 22%, p <0.0001), multivessel coronary disease (50% vs 39%, p <0.01), overall in-hospital mortality (8.4% vs 3.7%, p <0.01), cardiac mortality rate (6.1% vs 3.1%, p <0.05), and noncardiac mortality rate (2.3% vs 0.6%, p <0.05). Successful reperfusion was achieved in both groups at a
similarly high rate (93% and 95%, p ⴝ NS). Hospital mortality was similar whether reperfusion was successful or failed. Successful compared with unsuccessful angioplasty decreased mortality rates in the older (6.6% vs 33%, p <0.0001) and younger (3.0% vs 18%, p <0.0001) groups. When reperfusion was successful, the cardiac mortality rate in older patients was not significantly higher than in younger patients: 4.1% vs 2.4%, p ⴝ NS. 䊚2002 by Excerpta Medica, Inc. (Am J Cardiol 2002;89:797– 800)
irect coronary angioplasty expands the reperfusion population to include many patients that D would be considered ineligible for thrombolysis be-
injected into the infarct-related artery to rule out possible coronary spasm involvement; 162 mg of chewable aspirin was given before angioplasty. The balloon was inflated 2 or 3 times for 60 seconds at a pressure ranging from 6 to 10 atm routinely. Adjunctive stent implantation was performed if (1) the residual diameter stenosis was ⱖ30%, (2) there was complex coronary dissection, and (3) the anatomy was suitable for stenting (adequate vessel size and suitable focal lesion). The stents were routinely deployed at a pressure ranging from 6 to 16 atm, and for angiographic optimization, adjunctive high-pressure balloon dilation was performed if necessary. After angioplasty, all patients were admitted to the coronary care unit where 500 IU/hour of intravenous heparin drip for at least 48 hours and 162 or 243 mg/day of oral aspirin were given; 200 mg/day ticlopidine was added in patients who had stents. Reperfusion was considered successful if residual lumen diameter stenosis was ⬍50% with Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow.11 Causes of mortality: In-hospital mortality was divided into cardiac and noncardiac mortality. In addition, causes of cardiac mortality were classified into cardiogenic shock (if hemodynamic state could not be restored), congestive heart failure (if the patient died with pulmonary edema, hepatomegaly, peripheral edema, pleural effusion, or ascites), myocardial rupture, and arrhythmia. Cardiogenic shock was defined as systolic blood pressure ⬍90 mm Hg, peripheral signs of vascular collapse, decreased urinary output, and disturbance of consciousness. Statistical analysis: Values are expressed as mean ⫾ SD. Categorical variables were analyzed by chisquare test. Serial paired numerical data were com-
cause of high risk of intracranial hemorrhage.1–10 This retrospective study compares the benefits of direct coronary angioplasty in patients aged ⱖ75 years with those in patients aged ⬍75 years during acute myocardial infarction (AMI).
METHODS
Patient population: All consecutive patients with AMI who underwent direct coronary angioplasty within 24 hours of onset of symptoms or beyond 24 hours if myocardial ischemic symptoms persisted, treated at Kokura Memorial Hospital between January 1994 and December 1998, were entered in this analysis. Patients met the following criteria: (1) ST-segment elevation or depression in the electrocardiogram consistent with AMI, (2) symptoms of myocardial ischemia lasting ⬎20 minutes, and (3) creatine kinase elevation to ⬎2 times the normal value. Patients were divided according to age into ⱖ75 and ⬍75, defined as older and younger patients. Direct coronary angioplasty: Emergency coronary angiography and angioplasty were performed by the percutaneous femoral approach. Heparin (10,000 U) was administered when arterial access was secured. After visualizing both the left and right coronary arteries, 2.5 mg of isosorbide dinitrate was selectively From Kokura Memorial Hospital, Kitakyushu, Japan. Manuscript received September 18, 2001; revised manuscript received and accepted December 20, 2001. Address for reprints: Masakiyo Nobuyoshi, MD, Kokura Memorial Hospital, 1-1 Kifune-machi, Kokurakita-ku, Kitakyushu, Japan 8028555. E-mail: [email protected]. ©2002 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 89 April 1, 2002
0002-9149/02/$–see front matter PII S0002-9149(02)02187-2
797
TABLE 1 Patient Characteristics and Outcomes Patients Characteristics Age (yrs) Women Systemic hypertension Diabetes mellitus Hyperlipidemia* Prior myocardial infarction Infarct-related artery Left anterior descending Right Left circumflex Left main Saphenous vein graft Multivessel coronary disease Time from onset of symptoms to angioplasty (h) Procedural outcomes Stenting Successful reperfusion In-hospital mortality and causes of death Overall mortality Cardiac mortality Cardiogenic shock Congestive heart failure Myocardial rupture Arrhythmia Noncardiac mortality
ⱖ75 yrs (n ⫽ 261)
⬍75 yrs (n ⫽ 802)
80.8 ⫾ 4.6 124 (47.5%) 137 (52.5%) 67 (25.7%) 22 (8.4%) 28 (10.7%)
61.2 ⫾ 9.3 180 (22.4%) 333 (41.5%) 201 (25.1%) 134 (16.7%) 98 (12.2%)
⬍0.0001 ⬍0.0001 ⬍0.01 NS ⬍0.01 NS
116 (44.4%) 117 (44.8%) 25 (9.6%) 2 (0.8%) 1 (0.4%) 131 (50.2%) 12.3 ⫾ 24.7
398 (49.6%) 267 (33.3%) 117 (14.6%) 12 (1.5%) 8 (1.0%) 314 (39.2%) 11.3 ⫾ 33.3
NS ⬍0.001 ⬍0.05 NS NS ⬍0.01 NS
105 (40.2%) 243 (93.1%)
332 (41.4%) 762 (95.0%)
22 16 8 4 2 2 6
(8.4%) (6.1%) (3.1%) (1.5%) (0.8%) (0.8%) (2.3%)
30 25 18 3 3 2 5
(3.7%) (3.1%) (2.2%) (0.4%) (0.4%) (0.2%) (0.6%)
p Value
NS NS ⬍0.01 ⬍0.05 NS ⬍0.05 NS NS ⬍0.05
*With therapy and/or total cholesterol level ⬎220 mg/dl or triglyceride level ⬎150 mg/dl.
less likely to have a history of hyperlipidemia (8.4% vs 16.7%, p ⬍0.01). The right coronary artery was the infarct-related artery significantly more often and the left circumflex artery was involved significantly less often in the older group. Multivessel coronary disease was significantly more prevalent in the older patients (50.2% vs 39.2%, p ⬍0.01).
Direct coronary angioplasty (Table 1): Stenting was required as fre-
quently in older as in younger patients (40.2% vs 41.4%, p ⫽ NS). Successful reperfusion was achieved in 243 older (93.1%) and in 762 younger (95.0%) patients. In-hospital mortality and causes of death (Table 1): Older patients had a
significantly higher incidence of cardiac (p ⬍0.05), noncardiac (p ⬍0.05), and overall mortality (p ⬍0.01) than younger patients. Among the cardiac deaths, only congestive heart failure had a significantly higher incidence in the older patients (p ⬍0.05).
Does successful reperfusion alter in-hospital mortality? (Figure 1): Suc-
cessful direct coronary angioplasty decreased the in-hospital mortality rate significantly in both groups (p ⬍0.0001).
Does successful reperfusion alter the nature of in-hospital mortality? (Figure 2): Sixteen of 243 older patients with
FIGURE 1. In-hospital mortality of patients with successful reperfusion compared with those with unsuccessful reperfusion in both groups.
pared by the paired t test, and other continuous variables by the unpaired t test. A p value ⬍0.05 was regarded as significant.
RESULTS
Patient characteristics (Table 1): There were some baseline differences: 47.5% of the older patients and 22.4% of the younger patients were women (p ⬍0.0001). Older patients were more likely to have a history of systemic hypertension (52.5% vs 41.5%, p ⬍0.01) and 798 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 89
successful reperfusion (6.6%) died in the hospital: 10 (4.1%) of cardiac and 6 (2.5%) of noncardiac causes. Of 762 younger patients with successful reperfusion, 23 (3.0%) died in the hospital: 18 (2.4%) were cardiac and 5 (0.7%) noncardiac deaths. Thus, older patients had a significantly higher incidence of noncardiac and overall mortality than younger patients (p ⬍0.05), but the cardiac mortality rate was as low in younger patients when successful reperfusion was achieved. Does reperfusion failure affect the nature of in-hospital mortality? (Figure 3): Of 18 older patients with unsuc-
cessful reperfusion, 6 (33.3%) died in the hospital of cardiac causes; none died of noncardiac causes. All 7 younger patients with unsuccessful reperfusion died in the hospital from cardiac causes; none died of noncardiac causes. Reperfusion failure caused cardiac inhospital death regardless of age.
DISCUSSION Our results suggest that direct angioplasty should be undertaken regardless of age. Although successAPRIL 1, 2002
mortality in older patients was not higher than that in younger patients, provided that successful reperfusion was achieved. Reperfusion by direct angioplasty decreases the cardiac mortality rate regardless of age and should be implemented more aggressively, even in older patients, especially in those who are not suited for thrombolytic therapy.1–3 Study limitations: This study has several important limitations: (1) the study period of our patients was from 1994 to 1998. Improvements in hospital logistics, new devices,16 –19 and new drugs20 FIGURE 2. In-hospital mortality of older patients with successful reperfusion comhave been introduced since then, and the pared with that of younger patients with successful reperfusion with regard to advantages of direct angioplasty may cardiac, noncardiac, and overall mortality. become even greater21; (2) these results were achieved in an experienced investigational single center, and may not be applicable to all institutions. The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) angiographic substudy22 demonstrated the important link between survival of patients undergoing reperfusion and early attainment of complete (TIMI grade 3 flow) infarct artery patency. The tissue plasminogen activator regimen used preceded the acceptance of front loading, and this may have had an impact on vessel patency and clinical outcome.23 However, even with frontloaded tissue plasminogen activator, the restoration of TIMI grade 3 flow is still well below that achieved with diFIGURE 3. In-hospital mortality of older patients with unsuccessful reperfusion comrect angioplasty.2,22–24 Although the pared with that of younger patients with unsuccessful reperfusion with regard to results of direct angioplasty are related cardiac, noncardiac, and overall mortality. to the experience of performing physicians,25 results similar to the Primary ful reperfusion can be achieved in a high proportion Angioplasty in Myocardial Infarction (PAMI-I) trial26 of older patients (ⱖ75 years of age) and can greatly and the Netherlands study27,28 are achievable in decrease the overall in-hospital mortality rate to smaller, less experienced units by ensuring efficient 8.4%,12–14 this rate is still more than twice that in triage and prompt intervention.29 younger patients. Cardiac mortality due to congestive heart failure Acknowledgment: We are indebted to Alfonso-T was significantly higher in older patients,4,5 suggest- Miyamoto, MD, for his help with the manuscript. ing that the proposed therapeutic strategy would indeed be most effective in decreasing the mortality rate. De Boer et al15 compared direct angioplasty with 1. Himbert D, Juliard JM, Steg PG, Badaoui G, Baleynaud S, Le Guludec D, thrombolysis; direct angioplasty resulted in a lower Aumont MC, Gourgon R. Primary coronary angioplasty for acute myocardial with contraindication to thrombolysis. Am J Cardiol 1993;71:377–381. incidence of in-hospital mortality (2% vs 7%, p infarction 2. Grines CL, Browne KF, Marco J, Rothbaum D, Stone GW, O’Keefe J, Overlie ⬍0.05) and better left ventricular function (predis- P, Donohue B, Chelliah N, Timmis GC, et al. A comparison of immediate charge ejection fraction, 50% vs 45%; p ⬍0.001) than angioplasty with thrombolytic therapy for acute myocardial infarction. The Primary Angioplasty in Myocardial Infarction Study Group. N Engl J Med 1993; thrombolysis. Direct angioplasty salvages more myo- 328:673–679. cardium than thrombolytic therapy, thus preventing 3. Weaver WD, Litwin PE, Martin JS, Kudenchuk PJ, Maynard C, Eisenberg MS, MT, Cobb LA, Kennedy JW, Wirkus MS. Effect of age on use of thrombodevelopment of congestive heart failure, effective par- Ho lytic therapy and mortality in acute myocardial infarction. The MITI Project ticularly in the older population. Group. J Am Coll Cardiol 1991;18:657–662. The results of the present study confirm that direct 4. Delvin W, Cragg D, Jacks M, Friedman H, O’Neill W, Grines C. Comparison outcome in patients with acute myocardial infarction aged ⬎75 years with that coronary angioplasty in older patients effectively re- of in younger patients. Am J Cardiol 1995;75:573–576. duced in-hospital mortality to the point that cardiac 5. Paul SD, O’Gara PT, Mahjoub ZA, DiSalvo TG, O’Donnell CJ, Newell JB, CORONARY ARTERY DISEASE/ANGIOPLASTY FOR AMI IN OLDER PATIENTS
799
Villarreal-Levy G, Smith AJ, Kondo NI, Cararach M, Ferrer L, Eagle KA. Geriatric patients with acute myocardial infarction: cardiac risk factor profiles, presentation, thrombolysis, coronary interventions, and prognosis. Am Heart J 1996;131:710 –715. 6. Lew AS, Hod H, Cercek B, Shah PK, Ganz W. Mortality and morbidity rates of patients older and younger than 75 years with acute myocardial infarction treated with intravenous streptokinase. Am J Cardiol 1987;59:1–5. 7. Thiemann DR, Coresh J, Schulman SP, Gerstenblith G, Oetgen WJ, Powe NR. Lack of benefit for intravenous thrombolysis in patients with myocardial infarction who are older than 75 years. Circulation 2000;101:2239 –2246. 8. O’Connor CM, Califf RM, Massey EW, Mark DB, Kereiakes DJ, Candela RJ, Abbottsmith C, George B, Stack RS, Aronson L, Mantell S, Topol EJ. Stroke and acute myocardial infarction in the thrombolytic era: clinical correlates and longterm prognosis. J Am Coll Cardiol 1990;16:533–540. 9. de Jaegere PP, Arnold AA, Balk AH, Simoons ML. Intracranial hemorrhage in association with thrombolytic therapy: incidence and clinical predictive factors. J Am Coll Cardiol 1992;19:289 –294. 10. Simoons ML, Maggioni AP, Knatterud G, Leimberger JD, de Jaegere P, van Domburg R, Boersma E, Franzosi MG, Califf R, Schroder R, Braunwald E. Individual risk assessment for intracranial hemorrage during thrombolytic therapy. Lancet 1993;342:1523–1528. 11. TIMI Study Group. The Thrombolysis In Myocardial Infarction (TIMI) trial. N Engl J Med 1985;312:932–936. 12. Lee TC, Laramee LA, Rutherford BD, McConahay DR, Johnson WR Jr, Giorgi LV, Ligon RW, Hartzler GO. Emergency percutaneous transluminal coronary angioplasty for acute myocardial infarction in patients 70 years of age and older. Am J Cardiol 1990;66:663–667. 13. Yabe Y, Muramatsu T, Nakano H, Wagatsuma K. Efficacy and issues of emergent percutaneous transluminal coronary angioplasty. Comparison of clinical results in younger and elderly patients. Angiology 1995;46:1085–1095. 14. Laster SB, Rutherford BD, Giorgi LV, Shimshak TM, McConahay DR, Johnson WL Jr, Huber KC, Ligon RW, Hartzler GO. Results of direct percutaneous transluminal coronary angioplasty in octogenarians. Am J Cardiol 1996; 77:10 –13. 15. de Boer MJ, Hoorntje JC, Ottervanger JP, Reiffers S, Suryapranata H, Zijlstra F. Immediate coronary angioplasty versus intravenous streptokinase in acute myocardial infarction: left ventricular ejection fraction, hospital mortality and reinfarction. J Am Coll Cardiol 1994;23:1004 –1008. 16. Stone GW, Brodie BR, Griffin JJ, Morice MC, Costantini C, St. Goar FG, Overlie PA, Popma JJ, McDonnell J, Jones D, O’Neill WW, Grines CL. A prospective, multicenter study of the safety and feasibility of primary stenting in acute myocardial infarction: in-hospital and 30 day results of the PAMI Stent Pilot Trial. J Am Coll Cardiol 1998;31:23–30. 17. Suryapranata H, van’t Hof AW, Hoorntje JC, de Boer MJ, Zijlstra F. Randomized comparison of coronary stenting with balloon angioplasty in selected patients with acute myocardial infarction. Circulation 1998;97:2502–2505. 18. Nakagawa Y, Matsuo S, Kimura T, Yokoi H, Tamura T, Hamasaki N, Nosaka H, Nobuyoshi M. Thrombectomy with AngioJet catheter in native coronary
800 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 89
arteries for patients with acute or recent myocardial infarction. Am J Cardiol 1999;83:994 –999. 19. Rosenschein U, Roth A, Rassin T, Basen S, Laniado S, Miller HI. Analysis of coronary ultrasound thrombolysis endpoints in acute myocardial infarction (ACUTE Trial). Circulation 1997;95:1411–1416. 20. Brener SJ, Barr LA, Burchenal JEB, Katz S, George BS, Jones AA, Cohen ED, Gainey PC, White HJ, Cheek HB, et al, on behalf of the ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators. Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. Circulation 1998;98:734 – 741. 21. Schomig A, Kastrati A, Dirschinger J, Mehilli J, Schricke U, Pache J, Martinoff S, Neumann FJ, Schwaiger M. Coronary stenting plus platelet glycoprotein IIb/IIIa blockade compared with tissue plasminogen activator in acute myocardial infarction. N Engl J Med 2000;343:385–391. 22. The GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 1993;329:1615– 1622. 23. The GUSTO Investigators. An intertnational randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329: 673–682. 24. The Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) Angioplasty Substudy Investigators. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. N Engl J Med 1997;336:1621–1628. 25. Grassman ED, Johnson SA, Krone RJ. Predictors of success and major complications for percutaneous transluminal coronary angioplasty in acute myocardial infarction. An analysis of the 1990 to 1994 Society for Cardiac Angiography and Interventions Registries. J Am Coll Cardiol 1997;30:201–208. 26. Nunn CM, O’Neill WW, Rothbaum D, Stone GW, O’Keefe J, Overlie P, Donohue B, Grines L, Browne KF, Vlietstra RE, Catlin T, Grines CL, for The Primary Angioplasty in Myocardial Infarction I Study Group. Long-term outcome after primary angioplasty: report from the primary angioplasty in myocardial infarction (PAMI-I) trial. J Am Coll Cardiol 1999;33:640 –646. 27. Zijlstra F, de Boer MJ, Hoorntje JC, Reiffers S, Reiber JH, Suryapranata H. A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N Engl J Med 1993;328:680 –684. 28. Zijlstra F, Hoorntje JC, de Boer MJ, Reiffers S, Miedema K, Ottervanger JP, van’T Hof AW, Suryapranata H. Long-term benefit of primary angioplasty as compared with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1999;341:1413–1419. 29. Zahn R, Schiele R, Schneider S, Gitt AK, Wienbergen H, Siedl K, Bossalleer C, Buttner HJ, Gottwik M, Altmann E, Rosahl W, Senges J, for the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA), and the Myocardial Infarction Registry (MIR) Study Groups. Decreasing hospital mortality between 1994 and 1998 in patients with primary angioplasty but not in patients treated with intravenous thrombolysis. J Am Coll Cardiol 2000;36:2064 –2071.
APRIL 1, 2002