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Patient selection for percutaneous transluminal coronary angioplasty in acute myocardial infarction
Patient Selection for Percutaneous Transluminal Coronary Angioplasty in Acute Myocardial Infarction Spencer B. King III, MD
p
rogress in the treatment of patients with acute myocardial infarction has been impressive. The advent of coronary care units, electrical defibrillation, antiarrhythmic drugs, therapy for congestive heart failure, hemodynamic alterations and left ventricular function, and reperfusion strategies have resulted in a dramatic decrease in the mortality rate. A logical conclusion to such a scenario might be the direct reopening of coronary vessels by mechanical means during angioplasty. However, this paper will not be a defense of angioplasty as primary therapy for acute myocardial infarction. At this point, primary angioplasty for infarction has not been proved superior to thrombolytic therapy followed by properly selected reperfusion strategies. However, primary angioplasty has not been adequately studied in this regard, and with the advent of new reperfusion techniques, it may regain a prominent place in the treatment of acute coronary obstructions. Angioplasty was initially designed to treat stable coronary lesions. The success of this approach has been well documented, and angioplasty is now performed in more than 200,000 patients each year. Several studies have documented an excellent long-term survival rate in patients undergoing angioplasty. In a Zurich study, 1 patients undergoing angioplasty for the first time had a 7year survival rate of 96%. Similar patients undergoing angioplasty at Emory University in 1981 and followed up for 5 years had a 98% survival rate. 2 The patients in these studies were primarily those with 1-vessel disease. It is well known that surgery has its greatest effect on the prognosis of patients with severe coronary disease, principally left main and 3-vessel disease. Thus, surgery is ordinarily preferred in these patients. For the middle ground of patients with coronary disease, there is a need to determine whether angioplasty or surgery is the best strategy. Several studies, including the Emory Angioplasty versus Surgery Trial (EAST) and the Bypass Angioplasty Revascularization Investigation (BARI) trial, have been started by the National Heart, Lung, and Blood Institute. Both trials will enroll patients with multivessel disease who require revascularization and are suitable for either coronary bypass surgery or coronary angioplasty. The primary end point in the EAST trial will be a functional assessment by thallium stress testing to reveal the degree of ischemia, relating it Fromthe Divisionof Cardiology,Departmentof Medicineand Radiol- to the coronary angiographic documentation of revascuogy,EmoryUniversityHospital,Atlanta,Georgia. Addressfor reprints:SpencerB. KingIII, MD, AndreasGruentzig larization. The BARI trial, a larger study involving 15 CardiovascularCenter,Suite $606, EmoryUniversityHospital, 1364 centers, will use mortality as its primary end point. Both CliftonRoadNE, Atlanta,Georgia30322. trials will provide data on the rates of progression, the Whether thromhelytic therapy or immediate angioplasty should be the preferred treatment for patients with acute myocardial infarction has not yet been decided. Emergency angioplasty can be used as primary therapy, as an adjunct to thrombolytic therapy, or as a salvage procedure in patients in whom thrombolysis fails. Immediate angioplasty produces a higher recanalization rate, yet reclosure is more likely with this procedure. In many cases, patient selection for acute angioplasty remains controversial. Randomized trials comparing the results of thrombolysis with those of angioplasty are needed before definitive decisions can be made. (Am J Cardiol 1989;64:22B-24B)
Z2B
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME64
need for subsequent bypass surgery in the angioplasty group, and the overall cost of the 2 treatment strategies.
could identify ischemic but viable myocardium is needed in the acute phase of a myocardial infarction.
ANGIOPLASTY IN ACUTE MYOCARDIAL INFARCTION Although questions are being answered about patients with multivessel disease, the question remains, what is the role for angioplasty in acute myocardial infarction? There are several areas in which angioplasty may be of benefit. First, angioplasty can be used as a primary therapy at the time of acute myocardial infarction in order to open the artery as quickly as possible. Second, it can be performed immediately after thrombolytic therapy in patients in whom thrombolysis was unsuccessful (which occurred in 25% of patients in the Thrombolysis in Myocardial Infarction [TIMI] trial). Angioplasty can also be performed later in the hospital stay or at some future date to further dilate a culprit lesion or other vessels in a patient with residual obstruction after thrombolysis. What are the advantages of proceeding directly to angioplasty in patients with acute myocardial infarction? One advantage is the opportunity to establish a definitive diagnosis. With immediate catheterization, the coronary anatomy is defined, the patient can be immediately classified according to risk, and therapeutic decisions can be made on firm grounds. If thrombolysis has been ineffective in restoring anterograde blood flow, which occurs in approximately 25% of patients, then immediate angioplasty will be successful in a large number of these patients. Initial results from the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) triaP indicate that angioplasty in such patients produces an open artery, but there was a high in-hospital closure rate. The TAMI investigators are currently studying combination therapy with tissue plasminogen activator and urokinase in an effort to reduce the in-hospital closure rate. Such efforts in TAMI-5 have produced encouraging preliminary results. In contrast, the disadvantages of immediate catheterization and angioplasty after thrombolysis include increased bleeding and the potential for other complications. The major trials--the TAMI trial, 3 the TIMI trial, 4 and the European Cooperative Study GroupS--found that immediate angioplasty after thrombolysis is associated with a higher in-hospital mortality rate than with delayed angioplasty. Also, immediate angioplasty, which is expensive, is an impractical method in most settings because it necessitates round-the-clock coverage by the catheterization laboratory staff. Given the fact that thrombolysis is capable of opening the arteries of only 75 to 80% of patients, the use of angioplasty when thrombolysis is unsuccessful--socalled salvage angioplasty--remains interesting. Among the patients at a particularly high risk if thrombolysis is unsuccessful are those with an anterior infarction, particularly if prior inferior Q waves are present on the cardiogram. Patients with hemodynamic instability are also likely to benefit from immediate catheterization and revascularization. However, a more definitive test that
ANGIOPLASTY VERSUS THROMBOLY'rlC THERAPY Can angioplasty be used primarily as a substitute for thrombolysis? Certain advantages are obvious. Angioplasty without thrombolysis would reduce bleeding complications and result in a higher recanalization rate, with 85 to 95% of the arteries being reopened immediately. However, abrupt reclosure is more likely with immediate angioplasty than with elective angioplasty. In addition, this approach may or may not decrease the ultimate rate of ischemic events. Can immediate angioplasty improve overall left ventricular function? If left ventricular function is improved early, does it have a positive effect on the survival rate? Is there a sustained improvement in left ventricular function? Is any late improvement seen? These are just some of the questions that remain to be answered. Disadvantages of immediate angioplasty are related to its practicality. Catheterization facilities are limited, especially at times when many patients with myocardial infarction are admitted. If therapy is delayed because catheterization crews are not available and laboratories must be set up, the advantage of angioplasty in providing prompt reperfusion is lost. Also, arrhythmias that occur in the catheterization laboratory can ordinarily be managed but may be quite injurious. Finally, no large controlled trials have compared primary angioplasty with thrombolytic therapy, which has been widely tested. Some observational studies of acute angioplasty have reported success rates of 80 to 90%. The mortality rate certainly exceeds that of elective angioplasty, but if open arteries are established and maintained, patients undergoing immediate angioplasty seem to do well. However, patients whose arteries are not open at the completion of the procedure do poorly. Rutherford and co-workers 6 have reported on the 1year survival rate of several subsets of patients undergoing primary angioplasty. Patients not in shock, younger than age 75, and who had a patent vessel at the end of the procedure had an excellent 1-year survival rate. Patients in cardiogenic shock, of course, had a much poorer prognosis. PATIENT SELECTION Recently, an Intersociety Commission of the American College of Cardiology and American Heart Association looked at indications for angioplasty. The commission recommended that only the artery responsible for the acute myocardial infarction be dilated during emergency angioplasty.7 If other arteries are dilated at the same time, the increased likelihood of abrupt reclosure involving several arteries may put the patient at markedly increased risk. The commission's report classified patients into 1 of 3 categories. Class 1 includes patients in whom coronary angioplasty is generally agreed on to be a reasonable therapy. Class 3 includes patients in whom angioplasty is THE AMERICAN JOURNAL OF CARDIOLOGY JULY 18, 1989
23B
A SYMPOSIUM: MYOCARDIAL iNFARCTION--DIRECTION FOR THE '90s
contraindicated, and class 2 comprises the middle ground of patients in whom angioplasty may or may not be of benefit. The class 1 indications for percutaneous transluminal coronary angioplasty in patients who have sustained myocardial infarction are rather limited. The indications include recurrent pain or documented ischemia in patients with lesions who are judged to have a high chance of success and a low chance of complications. Patients who have recurrent infarct-related artery ischemia in the hospital are obvious candidates for the procedure. Class 2 indications include much of what is currently being practiced. Even though the use of angioplasty in these patients is controversial, many physicians believe that angioplasty has a place in acute evolving myocardial infarction, either as an adjunct to thrombolytic therapy, as a salvage procedure in patients whose arteries fail to open, as follow-up therapy in patients who had thrombolysis several days previously and do not have high-grade residual lesions or, in the opinion of some, as primary therapy for acute myocardial infarction without thrombolysis. The contraindications generally agreed on for angioplasty include dilating lesions other than the infarctrelated artery early in the evolution of the infarction, dilating residual lesions that are not severe, and dilating lesions that are difficult to dilate or that carry a very high risk to the patient.
CONCLUSION It cannot be denied that the more quickly an artery is opened and the more quickly ischemia is relieved, the more likely that myocardial salvage will be achieved. In addition, if the artery can be maintained opened, the ultimate prognosis for the patient will be improved. Realistically, however, in most settings intravenous thrombolysis is more applicable than emergency angioplasty.
248
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 64-
Nonetheless, in facilities with cardiac catheterization units and for patients seen in the early hours of infarction, immediate angioplasty may be indicated. Clinical trials have not yet determined whether emergency angioplasty or thrombolytic therapy should be the preferred treatment. Randomized trials must be conducted that compare prompt thrombolytic therapy with immediate angioplasty in comparable patients. There should also be a strategy of providing reperfusion with interventional techniques, which may reduce reperfusion injury and thereby optimize the potential benefits of emergency angioplasty. Only after such trials are completed will it be possible to conclude whether emergency angioplasty for acute infarction should have a continuing role in the treatment of patients with acute myocardial infarction.
REFERENCES 1, Gruentzig AR, King SB, Schlumpf M, Siegenthaler W. Long-term follow-up after percutaneous transluminal coronary angioplasty: the early Zurich experience. N Engl J Med 1987;316.'1127--1132. 2. Talley JD, Hurst JW, King SB Ill, Douglas JS Jr, Roubin GS, Gruentzig AR, Anderson HV, Weintraub WS. Clinical outcome 5 years after attempted percutaneous transluminal coronary angioplasty in 427 patients. Circulation 1988; 77:820-829. 3. Topoi EJ, Califf RM, George BS, Kereiakes DJ, Abbottsmith CW, Candela R J, Lee KL, Pitt B, Stack RS, O'Neill WN. A randomized trial of immediate versus delayed elective angioplasty after intravenous tissue plasminogen activator in acute myocardial infarction. N Engl J Med 1987;317:581-588. 4. The TIMI study group. Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator in acute myocardial infarction. N Engl J Med 1989,618-627. 5, Van de Werf F. Lessons from the European cooperative recombinant tissuetype plasminogen activator (rt-PA) versus placebo trial. JACC 1988;12.'suppl A:14A-19A. 6. Rutherford BD, Hartzler GO, McConahay DR, Ligon RW, Johnson WL, Giorgi LV. Direct balloon angioplasty in myocardial infarction: long-term results (abstr). Circulation 1988;78:11:H-502. 7. ACC/AHA Task Force Report. Guidelines for percutaneeus transluminal coronary angioplasty. A report of the American College of Cardiology/American Heart Association Task Force on assessment of diagnostic and therapeutic cardiovascular procedures (subcommittee on percutaneous transluminal coronary angioplasty). JACC 1988;12:529-545.
p
rogress in the treatment of patients with acute myocardial infarction has been impressive. The advent of coronary care units, electrical defibrillation, antiarrhythmic drugs, therapy for congestive heart failure, hemodynamic alterations and left ventricular function, and reperfusion strategies have resulted in a dramatic decrease in the mortality rate. A logical conclusion to such a scenario might be the direct reopening of coronary vessels by mechanical means during angioplasty. However, this paper will not be a defense of angioplasty as primary therapy for acute myocardial infarction. At this point, primary angioplasty for infarction has not been proved superior to thrombolytic therapy followed by properly selected reperfusion strategies. However, primary angioplasty has not been adequately studied in this regard, and with the advent of new reperfusion techniques, it may regain a prominent place in the treatment of acute coronary obstructions. Angioplasty was initially designed to treat stable coronary lesions. The success of this approach has been well documented, and angioplasty is now performed in more than 200,000 patients each year. Several studies have documented an excellent long-term survival rate in patients undergoing angioplasty. In a Zurich study, 1 patients undergoing angioplasty for the first time had a 7year survival rate of 96%. Similar patients undergoing angioplasty at Emory University in 1981 and followed up for 5 years had a 98% survival rate. 2 The patients in these studies were primarily those with 1-vessel disease. It is well known that surgery has its greatest effect on the prognosis of patients with severe coronary disease, principally left main and 3-vessel disease. Thus, surgery is ordinarily preferred in these patients. For the middle ground of patients with coronary disease, there is a need to determine whether angioplasty or surgery is the best strategy. Several studies, including the Emory Angioplasty versus Surgery Trial (EAST) and the Bypass Angioplasty Revascularization Investigation (BARI) trial, have been started by the National Heart, Lung, and Blood Institute. Both trials will enroll patients with multivessel disease who require revascularization and are suitable for either coronary bypass surgery or coronary angioplasty. The primary end point in the EAST trial will be a functional assessment by thallium stress testing to reveal the degree of ischemia, relating it Fromthe Divisionof Cardiology,Departmentof Medicineand Radiol- to the coronary angiographic documentation of revascuogy,EmoryUniversityHospital,Atlanta,Georgia. Addressfor reprints:SpencerB. KingIII, MD, AndreasGruentzig larization. The BARI trial, a larger study involving 15 CardiovascularCenter,Suite $606, EmoryUniversityHospital, 1364 centers, will use mortality as its primary end point. Both CliftonRoadNE, Atlanta,Georgia30322. trials will provide data on the rates of progression, the Whether thromhelytic therapy or immediate angioplasty should be the preferred treatment for patients with acute myocardial infarction has not yet been decided. Emergency angioplasty can be used as primary therapy, as an adjunct to thrombolytic therapy, or as a salvage procedure in patients in whom thrombolysis fails. Immediate angioplasty produces a higher recanalization rate, yet reclosure is more likely with this procedure. In many cases, patient selection for acute angioplasty remains controversial. Randomized trials comparing the results of thrombolysis with those of angioplasty are needed before definitive decisions can be made. (Am J Cardiol 1989;64:22B-24B)
Z2B
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME64
need for subsequent bypass surgery in the angioplasty group, and the overall cost of the 2 treatment strategies.
could identify ischemic but viable myocardium is needed in the acute phase of a myocardial infarction.
ANGIOPLASTY IN ACUTE MYOCARDIAL INFARCTION Although questions are being answered about patients with multivessel disease, the question remains, what is the role for angioplasty in acute myocardial infarction? There are several areas in which angioplasty may be of benefit. First, angioplasty can be used as a primary therapy at the time of acute myocardial infarction in order to open the artery as quickly as possible. Second, it can be performed immediately after thrombolytic therapy in patients in whom thrombolysis was unsuccessful (which occurred in 25% of patients in the Thrombolysis in Myocardial Infarction [TIMI] trial). Angioplasty can also be performed later in the hospital stay or at some future date to further dilate a culprit lesion or other vessels in a patient with residual obstruction after thrombolysis. What are the advantages of proceeding directly to angioplasty in patients with acute myocardial infarction? One advantage is the opportunity to establish a definitive diagnosis. With immediate catheterization, the coronary anatomy is defined, the patient can be immediately classified according to risk, and therapeutic decisions can be made on firm grounds. If thrombolysis has been ineffective in restoring anterograde blood flow, which occurs in approximately 25% of patients, then immediate angioplasty will be successful in a large number of these patients. Initial results from the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) triaP indicate that angioplasty in such patients produces an open artery, but there was a high in-hospital closure rate. The TAMI investigators are currently studying combination therapy with tissue plasminogen activator and urokinase in an effort to reduce the in-hospital closure rate. Such efforts in TAMI-5 have produced encouraging preliminary results. In contrast, the disadvantages of immediate catheterization and angioplasty after thrombolysis include increased bleeding and the potential for other complications. The major trials--the TAMI trial, 3 the TIMI trial, 4 and the European Cooperative Study GroupS--found that immediate angioplasty after thrombolysis is associated with a higher in-hospital mortality rate than with delayed angioplasty. Also, immediate angioplasty, which is expensive, is an impractical method in most settings because it necessitates round-the-clock coverage by the catheterization laboratory staff. Given the fact that thrombolysis is capable of opening the arteries of only 75 to 80% of patients, the use of angioplasty when thrombolysis is unsuccessful--socalled salvage angioplasty--remains interesting. Among the patients at a particularly high risk if thrombolysis is unsuccessful are those with an anterior infarction, particularly if prior inferior Q waves are present on the cardiogram. Patients with hemodynamic instability are also likely to benefit from immediate catheterization and revascularization. However, a more definitive test that
ANGIOPLASTY VERSUS THROMBOLY'rlC THERAPY Can angioplasty be used primarily as a substitute for thrombolysis? Certain advantages are obvious. Angioplasty without thrombolysis would reduce bleeding complications and result in a higher recanalization rate, with 85 to 95% of the arteries being reopened immediately. However, abrupt reclosure is more likely with immediate angioplasty than with elective angioplasty. In addition, this approach may or may not decrease the ultimate rate of ischemic events. Can immediate angioplasty improve overall left ventricular function? If left ventricular function is improved early, does it have a positive effect on the survival rate? Is there a sustained improvement in left ventricular function? Is any late improvement seen? These are just some of the questions that remain to be answered. Disadvantages of immediate angioplasty are related to its practicality. Catheterization facilities are limited, especially at times when many patients with myocardial infarction are admitted. If therapy is delayed because catheterization crews are not available and laboratories must be set up, the advantage of angioplasty in providing prompt reperfusion is lost. Also, arrhythmias that occur in the catheterization laboratory can ordinarily be managed but may be quite injurious. Finally, no large controlled trials have compared primary angioplasty with thrombolytic therapy, which has been widely tested. Some observational studies of acute angioplasty have reported success rates of 80 to 90%. The mortality rate certainly exceeds that of elective angioplasty, but if open arteries are established and maintained, patients undergoing immediate angioplasty seem to do well. However, patients whose arteries are not open at the completion of the procedure do poorly. Rutherford and co-workers 6 have reported on the 1year survival rate of several subsets of patients undergoing primary angioplasty. Patients not in shock, younger than age 75, and who had a patent vessel at the end of the procedure had an excellent 1-year survival rate. Patients in cardiogenic shock, of course, had a much poorer prognosis. PATIENT SELECTION Recently, an Intersociety Commission of the American College of Cardiology and American Heart Association looked at indications for angioplasty. The commission recommended that only the artery responsible for the acute myocardial infarction be dilated during emergency angioplasty.7 If other arteries are dilated at the same time, the increased likelihood of abrupt reclosure involving several arteries may put the patient at markedly increased risk. The commission's report classified patients into 1 of 3 categories. Class 1 includes patients in whom coronary angioplasty is generally agreed on to be a reasonable therapy. Class 3 includes patients in whom angioplasty is THE AMERICAN JOURNAL OF CARDIOLOGY JULY 18, 1989
23B
A SYMPOSIUM: MYOCARDIAL iNFARCTION--DIRECTION FOR THE '90s
contraindicated, and class 2 comprises the middle ground of patients in whom angioplasty may or may not be of benefit. The class 1 indications for percutaneous transluminal coronary angioplasty in patients who have sustained myocardial infarction are rather limited. The indications include recurrent pain or documented ischemia in patients with lesions who are judged to have a high chance of success and a low chance of complications. Patients who have recurrent infarct-related artery ischemia in the hospital are obvious candidates for the procedure. Class 2 indications include much of what is currently being practiced. Even though the use of angioplasty in these patients is controversial, many physicians believe that angioplasty has a place in acute evolving myocardial infarction, either as an adjunct to thrombolytic therapy, as a salvage procedure in patients whose arteries fail to open, as follow-up therapy in patients who had thrombolysis several days previously and do not have high-grade residual lesions or, in the opinion of some, as primary therapy for acute myocardial infarction without thrombolysis. The contraindications generally agreed on for angioplasty include dilating lesions other than the infarctrelated artery early in the evolution of the infarction, dilating residual lesions that are not severe, and dilating lesions that are difficult to dilate or that carry a very high risk to the patient.
CONCLUSION It cannot be denied that the more quickly an artery is opened and the more quickly ischemia is relieved, the more likely that myocardial salvage will be achieved. In addition, if the artery can be maintained opened, the ultimate prognosis for the patient will be improved. Realistically, however, in most settings intravenous thrombolysis is more applicable than emergency angioplasty.
248
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 64-
Nonetheless, in facilities with cardiac catheterization units and for patients seen in the early hours of infarction, immediate angioplasty may be indicated. Clinical trials have not yet determined whether emergency angioplasty or thrombolytic therapy should be the preferred treatment. Randomized trials must be conducted that compare prompt thrombolytic therapy with immediate angioplasty in comparable patients. There should also be a strategy of providing reperfusion with interventional techniques, which may reduce reperfusion injury and thereby optimize the potential benefits of emergency angioplasty. Only after such trials are completed will it be possible to conclude whether emergency angioplasty for acute infarction should have a continuing role in the treatment of patients with acute myocardial infarction.
REFERENCES 1, Gruentzig AR, King SB, Schlumpf M, Siegenthaler W. Long-term follow-up after percutaneous transluminal coronary angioplasty: the early Zurich experience. N Engl J Med 1987;316.'1127--1132. 2. Talley JD, Hurst JW, King SB Ill, Douglas JS Jr, Roubin GS, Gruentzig AR, Anderson HV, Weintraub WS. Clinical outcome 5 years after attempted percutaneous transluminal coronary angioplasty in 427 patients. Circulation 1988; 77:820-829. 3. Topoi EJ, Califf RM, George BS, Kereiakes DJ, Abbottsmith CW, Candela R J, Lee KL, Pitt B, Stack RS, O'Neill WN. A randomized trial of immediate versus delayed elective angioplasty after intravenous tissue plasminogen activator in acute myocardial infarction. N Engl J Med 1987;317:581-588. 4. The TIMI study group. Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator in acute myocardial infarction. N Engl J Med 1989,618-627. 5, Van de Werf F. Lessons from the European cooperative recombinant tissuetype plasminogen activator (rt-PA) versus placebo trial. JACC 1988;12.'suppl A:14A-19A. 6. Rutherford BD, Hartzler GO, McConahay DR, Ligon RW, Johnson WL, Giorgi LV. Direct balloon angioplasty in myocardial infarction: long-term results (abstr). Circulation 1988;78:11:H-502. 7. ACC/AHA Task Force Report. Guidelines for percutaneeus transluminal coronary angioplasty. A report of the American College of Cardiology/American Heart Association Task Force on assessment of diagnostic and therapeutic cardiovascular procedures (subcommittee on percutaneous transluminal coronary angioplasty). JACC 1988;12:529-545.