American Heart Journal Founded in 1925

August 1990 Volume 120, Number 2

CLINICAL INVESTIGATIONS

Management comparison for acute myocardial infarction: Direct angioplasty versus sequential thrombolysis-angioplasty

To compare the results and outcome of different management approaches for acute myocardial infarction, we analyzed our experience with early (i.e., within 6 hours of infarct onset) direct percutaneous transluminal coronary angioplasty (group A) versus initial treatment with thrombolytic therapy (group B) followed by angioplasty. From 1982 to 1989 a total of 214 patients underwent primary angioplasty for acute myocardial infarction. During this time 157 patients underwent initial thrombolytic therapy, 104 with intravenous streptokinase and 53 with intravenous tissue-type plasminogen activator followed by angioplasty. Other than age (group A, 61.7 + 11.5 years; group B, 57.3 & 11.6 years; p = O.ODD2), the clinical characteristics of the groups were similar. In group A, 197 (92.1%) had successful results, and 17 (7.9%) were failures. Of the group treated with thrombolytic therapy, there was an overall 81.5% patency rate for patients treated with streptokinase and tissue-type plasminogen activator with no significant difference between the agents. Angioplasty success after thrombolytic therapy was 94.3%. In-hospital and l-year survival was significantly better in group B patients (95.5% and 95.5%, respectively) than in group A patients (92.1% and 89.3%, respectively). We conclude that both direct angioplasty and thrombolytic therapy followed by angioplasty provide high recanalization rates but that short- and long-term survival is improved when thrombolytic therapy precedes angioplasty in acute myocardial infarction patients. (AM HEART J 1990; 120:237.)

Gary D. Beauchamp, MD, James L. Vacek, MD, and Wayne Robuck. Kansas City, MO.

The treatment of acute myocardial infarction has undergone radical change in the last decade. Em- phasis has shifted from reducing myocardial oxygen demand during and immediately after the event to providing direct augmentation of supply by improv- ing perfusion to the area of infarction. The two pri- mary treatment methods have involved use of percu- taneous transluminal coronary angioplasty (PTCA) and thrombolytic therapy. Both modalities appear to provide markedly enhanced short-term and long- term survival compared with historical controls and groups treated by standard modalities as evaluated in recently published studies.lm7 In general, vessel pa- tency, postinfarction ejection fraction, in-hospital

From the Mid America Heart Institute, St. Luke’s Hospital, Kansas City, MO. and Mid-America Cardiology Associates (see Appendix).

Received for publication Feb. 12, 1990; accepted Mar. 20, 1990.

Reprint requests: James L. Vacek, MD, Mid-America Cardiology Associ- ates, 4320 Wornall, Suite 40-11, Kansas City, MO 64111.

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and l-year survival rates appear to be similar in groups that have been treated with PTCA compared with groups that have had thrombolytic ther- apy.lF 5y *-lo However, three recent studies have sug- gested that use of thrombolytic therapy as the pri- mary initial modality results in fewer complications and slightly better long-term survival than immedi- ate angioplasty after thrombolytic treatment.11-13 Initial studies focused on use of angioplasty as an adjunct to thrombolytic therapy with the concept that a patient with a residual high-grade lesion that remains after thrombolytic therapy should undergo angioplasty to reduce a residual significant stenosis. Exact timing of angioplasty after thrombolytic ther- apy has remained controversial, and the results of the previously mentioned studies suggest that it may be delayed from 18 hours to 7 days after thrombolytic therapy. Results of the recently published TIMI- study further suggest that routine coronary angiog- raphy and angioplasty of residual high-grade stenoses was unnecessary unless a patient showed spontane-

237

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American Heart Journal 23% Beauchamp, Vacek, and Robuck

Table 1. Patient characteristics

PTCA only patients Thrombolysis-PTCA patients

Males 159 (74%) 124 (79%) Females 55 (26%) 33 (21%) Total 214 157 Age* 61.7 + 11.5 yr (range 37-93) 57.3 I 10.6 yr (range 31-86)

Prior MI Yes No Yes No

Males 28 131 25 99

Females 6 49 5 28 Total (1%) 180 30 127

(84 % , (19%) (81%)

Prior CABG Yes No Yes No

Males 18 141 7 117 Females 4 51 1 32 Total 22 192 8 149

Diseased vessels Single Vessel 32 (15%) 36 (23%) Double Vessel 53 (25%) 43 (27%) Triple Vessel 129 (60%) 78 (50%)

Ejection fraction at initial catheterization

47.0 * 13.0% 47.7 k 13.8%

Infarct distribution

PTCA only patients Thrombolysis-PTCA Patients Both groups

Ant = 93 Inf = 121 Ant = 60 Inf = 97 Ant = 153 Inf = 218 (43%) (57%) (38%) (62%) (41%) (59%)

Ant, Anterior; Avg, average; CABG, coronary artery bypass grafting; Inf, inferior; Max, maximum; MI, myocardial infarction; Min, minimum; PTCA, per- cutaneous transluminal coronary angioplasty. *No significant difference existed between the groups for any variables other than age (p = 0.0002).

ous myocardial ischemia or had a positive predis- charge limited stress test for inducible ischemia.14 These findings have been confirmed by other investigators.15 Little comparative data exist on di- rect (i.e., primary, not after thrombolytic therapy) PTCA versus thrombolytic therapy followed by PTCA for acute myocardial infarction.16 We re- viewed our experience at a single medical center where both approaches were employed.

METHODS Patients. From 1982 to 1989 a total of 371 patients

sought treatment at our medical center within 6 hours of acute myocardial infarction. A total of 214 patients were treated with direct angioplasty, and 157 received throm- bolytic therapy followed by PTCA. Of the patients in the thrombolytic group, 104 patients received intravenous streptokinase, and 53 patients received intravenous tissue- type plasminogen activator (t-PA). Choice of treatment was made by the attending physician. Patient characteris- tics are noted in Table I.

Angioplasty. Percutaneous coronary angioplasty was usually performed via the femoral artery after diagnostic

coronary arteriography and ventriculography. A variety of guiding catheters and balloon dilatation catheters were used at the discretion of the physician who was performing the study. Angioplasty success was defined as reduction of stenosis by residual narrowing greater than 20% to less than 50%. In general, only the infarct-related vessel underwent dilatation. Inflated balloon diameter was matched to the estimated diameter of the adjacent vessel without disease. Multiple inflations were performed from 2 to 12 atm for periods that ranged from 20 to 90 seconds. Patients were premeditated with intravenous heparin (10,000 U), which was repeated at a dose of 5000 U every hour. Patients usually received premeditation with intra- venous lidocaine and calcium channel blockers, and after the procedure they received maintenance therapy that consisted of a continuous heparin infusion for periods that ranged from 8 hours to 4 days.

Thrombolytic therapy. Streptokinase was administered in an average dose of 1.5 million U infused over 1 hour. Tissue-type plasminogen activator was administered in an average dose of 100 U given over 3 hours (60 mg in hour 1, 20 mg each in hours 2 and 3). Heparin infusions were begun at the conclusion of the thrombolytic agent infusion and were continued for a total of 1 to 4 days. As-

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Number 2 Direct PTCA us thrombolysis/PTCA in AIkfI 239

pirin was not routinely used during the duration of the study.

Follow-up. Of the 214 patients who received direct an- gioplasty, 90 (42 % ) were recatheterized at a mean interval of 29 weeks, primarily for evidence of inducible ischemia on exercise stress testing or because of the onset of spontane- ous angina. Of the patients who underwent thrombolytic therapy, 49 (31% ) underwent repeat, angiographic evalua- tion at a mean time of 30 weeks after their infarcts for sim- ilar reasons. Patients were followed up clinically in the office.

Statistical analysis. Values are expressed as mean + 1 standard deviation unless otherwise noted. Statistics were analyzed with an SAS Rekase 5.16 package (SASInstitute, Inc., Cary, N.C.) on an IBM 3700 computer (IBM Corp., Health Industry Mktg. Div., Atlanta, Ga.). Student’s t test was used to compare continuous variables, whereas chi square analysis was used for discrete variables or compar- ison of group characteristics. Survival curves were gener- ated and compared with the Wilcoxon rank test for equal- ity of survival time. A p value i 0.05 was considered sig- nificant.

RESULTS

Patient characteristics. Table I presents patient de- mographics: infarct distribution, number of involved vessels, initial ejection fraction, prior bypass surgery and infarcts for the total group, as well as the num- ber of males and females for each group. There was no significant difference between the groups for any variable other than age. The clinical impact of the 4- year mean age difference between the groups would most likely be small. Overall angioplasty success was 92.2 % for the direct angioplasty group and 94.3 % for thrombolysis-angioplasty group 07, NS). Elderly pa- tients were defined as those above the age of 70, and in this group there was an 88.6 % initial direct angio- plasty success rate and a 90.3 % thrombolysis-angio- plasty success rate (p, NS). In-hospital survival was 95.5% and l-year survival was 95.5% for the throm- bolysis-angioplasty group. (No patients in this group died in the first year after hospital discharge.) For the angioplasty group, in-hospital survival was 92.1% and l-year survival was 89.3 % . Mortality for patients in both groups is presented in Tables II and III. Both in-hospital and l-year survival were significantly better in the thrombolysis-angioplasty group.

Direct angioplasty. Of 214 patients who underwent direct angioplasty, 197 (92.1% ) procedures were considered successful and 17 (7.9 % ) were failures (Table IV). Of the failures, five patients died, six pa- tients successfully underwent coronary artery bypass grafting, and six patients were treated medically. Of the 197 patients judged to have successful angioplas- ty, 85 did not undergo subsequent restudy or bypass surgery and were alive at a mean of 57 weeks after their infarcts. Ninety patients underwent repeat an- giographic evaluation at a mean time of 31 weeks af- ter their myocardial infarctions for reasons of induc-

Table II. Mortality

Direct angioplasty Thrombolysis-PTCA

Time Deaths Time Deaths

<24 h 10 24 h 2 >24 h, <I wk 6 >24 h, <1 wk 3 >l wk (mean, 50 wk) 11 >l wk (mean, 134 wk) 5

Table III. Results of various management approaches for acute myocardial infarction

Approach In-hospital 1 -year

mortality mortality

*Direct angioplasty 111124 = 1.9% 231214 = 10.7% Initial thrombolysis followed 5132 = 15.6% 5132 = 15.6%

by early angioplasty (<24 h)

Initial thrombolysis followed 2/125 = 1.6% 2/125 = 1.6% by delayed angioplasty (>24 h)

*Total Thrombolysis- 71157 = 4.5% 71157 = 4.5% Angioplasty Group

*Mortality was significantly different between these groups for both in-hospital (p = 0.006) end l-year (p = 0.028) mortality.

ible ischemia at stress testing or spontaneous symp- toms of ischemia. Twenty-three patients underwent bypass surgery and were alive and well at a mean pe- riod of 86 weeks after their operations, whereas six patients died at a mean period of 26 weeks after they had undergone bypass surgery. Sixteen patients died and had not undergone bypass grafting. The occur- rence of symptoms and the results of treadmill test- ing for the 85 patients who did not undergo restudy are presented in Table V. Of the 90 patients who were restudied, 47 (52.2%) did not manifest evidence of restenosis at the site of angioplasty, whereas 43 (47.8%) were shown to have restenosis at the angio- plasty site. The patients who were shown to have restenosis comprised 21.8% of the total group who had undergone successful angioplasty (very likely an underestimation due to clinically unrecognized res- tenosis). Of the 43 patients who manifested evidence of restenosis, 28 (65.1%) underwent PTCA again with a 100% success rate.

Thrombolytic therapy. Of the 157 patients who un- derwent thrombolytic therapy, 104 were treated with intravenous streptokinase and 53 were treated with t-PA. Of these patients, 32 (20.4 % ) underwent early (within 24 hours of infarct) PTCA, and 125 (79.6% ) received delayed (1 to 4 days after infarct) PTCA (Table III). Overall vessel patency at catheterization was 81.5 % for both agents, (82.7 % for streptokinase and 79.2 % for t-PA, p, NS). In this group of 157 pa- tients who underwent angioplasty after thrombolytic

August 1990

240 Beauchamp, Vacek, and Robuck American Heart Journal

Table IV. Direct percutaneous transluminal coronary an- gioplasty outcome

Patients

Success 197 (92.1%) Alive, medical management

without restudy at a mean of 56 weeks post MI

Alive, restudy at mean of 31 weeks post MI (23 underwent successful bypass surgery)

Died, after bypass surgery Died, without bypass surgery Total

Failures 17 (7.9%) Dead Bypass surgery Medical treatment Total

Total patients

85

90

6 16

197

5 6 6

17 214

Table V. Direct PTCA: clinical follow-up of 85 patients treated medically without angiographic follow-up

Not Mean

Positive Negative available weeks

Angina 2 78 5 56 Treadmill 3 70 12 54

Maximum follow up, 217 weeks; average follow-up, 56 weeks.

therapy, 148 (94.3%) of the PTCAs were considered successful, whereas 9 (5.7%) were failures (p, NS compared with direct PTCA group). Of the failures, four patients were treated medically, three patients underwent successful coronary artery bypass graft- ing (CABG), and two patients died (one during emergency CABG). Of the 148 patients who were judged to have successful angioplasty after throm- bolysis, 90 did not undergo subsequent restudy, whereas 49 patients underwent repeat angiographic evaluation at a mean time of 30 weeks after PTCA for reasons of inducible ischemia at stress testing or spontaneous symptoms of ischemia. Six patients died, two during bypass surgery. Three patients un- derwent bypass surgery and were alive and well at a mean period of 50 weeks after their operations. Of the 90 patients who did not undergo restudy, all were alive and had not undergone bypass surgery at a mean of 53 weeks after their infarcts (Table VI).

Of the 49 patients who were restudied, 23 (46.9 % ) did not manifest evidence of restenosis at the site of postthrombolytic angioplasty, but 26 (53.1% ) were shown to have restenosis at the angioplasty site. The

Table Vi. Thrombolysis-PTCA group: clinical follow-up of 90 patients treated medically without angiographic follow- up

Not Mean Positive Negative available weeks

Angina 3 77 10 53 Treadmill 6 70 14 51

Maximum follow-up, 315 weeks; average follow-up, 53 weeks.

patients who were shown to have restenosis com- prised 17.6% of the total group who had thrombol- ysis followed by successful angioplasty. There was no significant difference in documented restenosis rates between the groups. Of the 26 patients who showed evidence of restenosis, 23 (88.5%) underwent PTCA again with a 100% success rate. One patient under- went coronary artery bypass grafting, and two pa- tients were treated with medication.

DISCUSSION

In the prereperfusion coronary care unit era, in- hospital mortality after myocardial infarction aver- aged 10% to 20%. 17-20 In recent studies that have employed thrombolytic therapy within 6 hours of in- farct, control group in-hospital mortalities have ranged from 5.7% to 14.1% .21p 22 The in-hospital mortality of patients in our group who received sequential thrombolytic-PTCA therapy (4.5 % for total group, 1.6% for those who received delayed PTCA) is comparable to the best previously reported results for thrombolytic and sequential thrombolytic PTCA treatment groups 4y 7~ g-14 (Table III). Likewise, our direct PTCA results are comparable to those re- ported in previous studies.lp 5p 6 In addition to direct reperfusion of occluded infarct-related vessels, other treatments have undoubtedly affected survival im- provement. These include arrhythmia monitoring and control, treatment for heart failure, and more widespread employment of anti-ischemic agents such as nitrates, B-blockers, and calcium antagonists. As- pirin has been shown to have a beneficial effect on postinfarction mortality, although this agent has only recently begun to be routinely used.7 Results of previous studies have suggested a significant im- provement in survival when either angioplasty is a primary sole therapy, ls 5, 6 when angioplasty follows thrombolytic therapy,11-13 or when thrombolytic ther- apy alone is used.4l 7, g, lop l4 Although several studies have addressed the timing of and need for PTCA af- ter thrombolysis, little data exist on direct angio- plasty versus thrombolytic therapy followed by PTCA. Although our study population was not pro-

Volume 120

Number 2

spectively randomized between the treatment meth- ods, examination of clinical characteristics of the two groups revealed that they are comparable. III terms of achieved vessel patency, the results of direct PTCA and thrombolytic therapy followed by PTCA are similar, although both short- and long-term sur- vival is significantly better in the sequential therapy group.

Although treatment outcomes for both direct an- gioplasty and sequential thrombolytic-PTCA ther- apy are comparable, applicability on a nationwide basis is very different. 23-27 Only a small proportion of patients may be treated by the direct angioplasty approach because of the necessity for around-the- clock availability of a cardiac catheterization labora- tory, experienced operators, and attendants. On the other hand, thrombolytic therapy may be adminis- tered in most hospital emergency rooms or critical care unit settings and in the future may be amenable to administration by paramedic units in the field. As previous studies have suggested, in-hospital and l-year mortality after thrombolytic therapy alone without routine angiography or angioplasty of resid- ual high-grade lesions in asymptomatic patients without inducible ischemia is similar to that of patients who undergo routine angiography and angioplasty.143 l5 The chief remaining question about optimal treatment for reperfusion in acute myocar- dial infarction rests on the relative roles of direct an- gioplasty where available, as compared with sequen- tial thrombolytic-PTCA therapy. Our data would suggest that direct angioplasty, although highly suc- cessful, confers no clinical outcome benefit over sequential therapy for most patients. Concern that sequential therapy may result in inferior results compared with direct PTCA because of plaque a:nd myocardial hemorrhage caused by the thrombolytic agent is not borne out by our study.l Specific situa- tions, such as continued ischemia after failed throm- bolytic therapy or cardiogenic shock, may benefit from angioplasty.

Limitations. Although our patient population rep- resents a large group of patients who were treated by a single group of cardiologists, the patients’ therapy was not randomized. However, the similarity of clin- ical parameters suggests that the groups were com- parable.

Conclusions. Both direct angioplasty and throm- bolytic therapy provide excellent reperfusion success for acute myocardial infarction. Widespread avail- ability for a larger number of patients, cost consider- ations, and better short- and long-term survival sug- gest that initial thrombolytic therapy is an appropri- ate treatment for a majority of patients with acute myocardial infarctions. The necessity and timing of

Direct PTCA us thrombolysis/PTCA in AMI 24 1

PTCA after thrombolysis may be inferred from the results of previous and future studies as well as from the presentation and clinical course of individual pa- tients.

The authors would like to thank Ken Gerald for expert statis- tics support and Jean Oberhaus for assistance with the manu- script.

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APPENDIX

The members of Mid-America Cardiology Associ- ates are: Hubert H. Bell, MD Lynn H. Kindred, MD Gary D. Beauchamp, MD James J, Harbrecht, MD Loren D. Berenbom, MD Charles B. Porter, MD Paul H. Kramer, MD Linda J. Crouse, MD Douglas J. Willhoite, MD H. William Stites, MD Steven D. Owens, MD Thomas L. Rosamond, MD A. Jody Rowland, MD James L. Vacek, MD

August 1990 American Heart Journal