Asymptomatic Cardiac Ischemia Pilot (ACIP) Study
Improvement of Cardiac Ischemia at 1 Year After PTCA and CABG
Background Cardiac ischemia on the ambulatory ECG (AECG) and/or on the exercise treadmill test (ETT) is associated with an increased risk of adverse outcome. Myocardial revascularization more often suppresses cardiac ischemia than does medical management alone. However, few studies have compared the effects of percutaneous transluminal coronary angioplasty (PTCA) with those of coronary artery bypass grafting (CABG) on cardiac ischemia and clinical outcome.
Methods and Results A total of 558 patients were randomly assigned to one of three treatment strategies in the Asymptomatic Cardiac Ischemia Pilot (ACIP) study: angina-guided medical strategy (n=184), ischemia-guided medical strategy (n=182), or revascularization (n=192). In patients assigned to revascularization, the choice of the procedure, PTCA or CABG, was made by the clinical unit staff and patient based on a coronary angiogram usually performed within 2 months of enrollment. CABG was selected in 78 patients and PTCA in 92 patients. At 12 weeks, ischemia on the AECG was suppressed in 70% of CABG patients versus 46% of PTCA patients (P=.002). Ischemia on the ETT was no longer present in 46% versus 23% of the patients, respectively (P=.005). Angina, within 4 weeks of the follow-up visit, was absent in 90% versus 68%, respectively (P=.001). These clinical variables remained improved in both groups at 1 year. Clinical events (myocardial infarction or repeat revascularization) occurred in 1 CABG patient versus 7 PTCA patients at 12 weeks, and in 1 versus 16 patients, respectively, at 12 months (P<.001).
Conclusions Ischemia on the AECG and ETT and angina were relieved in many patients after both procedures; however, CABG was superior to PTCA, and it was associated with a lower incidence of clinical events at 1 year. These results suggest that more complete revascularization relates to better clinical outcome. However, a large trial is needed to confirm these results.
Cardiac ischemia documented on the AECG and/or on the ETT has been associated with an increased risk of adverse clinical outcome.1 2 3 4 While cardiac ischemia can be suppressed by medical therapy and by myocardial revascularization in a high percentage of patients, it has been shown in the ACIP study recently that revascularization is superior to medical management alone in the relief of cardiac ischemia.5 Whether this increased efficacy will result in a better clinical outcome, however, remains to be demonstrated in larger mortality and morbidity trials.
The relative efficacy and safety of PTCA compared with those of CABG in the suppression of cardiac ischemia have not been adequately documented prospectively. A recent ACIP report suggests that CABG is superior to PTCA in the early suppression of cardiac ischemia.6 However, it is not known whether this improvement persists over time. The purpose of this report is to describe the effects of PTCA versus CABG on cardiac ischemia and clinical events during the first year after revascularization in patients enrolled in the ACIP study and randomized to revascularization.
Details of the ACIP study design have been described previously.7 8 Briefly, patients who had angiographic evidence of obstructive coronary artery disease (≥50% diameter stenosis), evidence of stress-related ischemia during an ACIP ETT (or an alternative stress test if the patient could not exercise), and one episode or more of asymptomatic cardiac ischemia (≥1-mm ST-segment deviation from baseline, lasting ≥1 min, and separated from other episodes by at least 5 minutes) on a 48-hour AECG were eligible for enrollment in ACIP. After giving informed consent, they were randomly assigned to one of three treatment strategies: angina-guided medical strategy with titration of anti-ischemia medication to relieve symptoms (n=184), ischemia-guided medical strategy with titration of anti-ischemia medication to eliminate both angina and AECG ischemia (n=182), or revascularization of all important stenoses in major coronary arteries (n=192).
Patients assigned to revascularization were to undergo either PTCA or CABG within 4 weeks (6 weeks if staged angioplasty was performed) of the baseline qualifying visit. The goal was to achieve correction of all important stenoses in major coronary arteries. The choice of PTCA or CABG was made by the clinical unit staff and patient, based on coronary angiography usually performed within 2 months of revascularization. In general, CABG was considered for patients with multivessel disease and PTCA for patients with single-vessel disease or multivessel disease when the important lesions in major coronary arteries were suitable for coronary angioplasty.
Angiographic characteristics making surgery preferable were diffuse coronary disease with lesions >20 mm in length, excessive tortuosity or angulation of the involved artery, occluded arteries, inability to protect major side branches, and lesions located so that abrupt vessel closure would result in high risk of cardiogenic shock.9
The patient was considered suitable for angioplasty if the lesions satisfied previously established guidelines.10 11 The immediate outcome of the intervention was classified as successful by the clinical unit staff if all attempted stenoses in major coronary arteries were reduced to <50% luminal diameter as measured by electronic calipers, and the patient was free of procedure-related complications such as death, myocardial infarction, or emergency CABG surgery. Anatomic success was defined by the Angiography Core Laboratory as a postangioplasty stenosis <50% for any lesion or for all lesions attempted.
Medical therapy after revascularization was based on local clinical practice. The patient’s management of angina after revascularization was changed to the ACIP regimen (atenolol/nifedipine or diltiazem/isosorbide dinitrate), assigned randomly, unless one regimen was contraindicated.5 7 8
In ACIP, the primary outcome measure was complete suppression of ischemic episodes on the 48-hour AECG obtained at the 12-week visit (84 to 182 days) after enrollment or approximately 8 weeks after revascularization. Secondary outcomes included other measures related to ischemia from the 48-hour AECG, ACIP protocol ETT, and clinical outcomes.
The protocol mandated a 48-hour AECG and an ACIP ETT (if done during screening) for all patients at the 12-week, 6-month, and 12-month visits. Anginal status was also assessed at those visits. Clinical outcome was documented for patients who died, who had a myocardial infarction, or who had nonprotocol revascularization. Patients who died, who had a myocardial infarction, or who had a nonprotocol repeat revascularization procedure before a scheduled visit were counted as having ischemia present on the 48-hour AECG at that visit, regardless of AECG findings. Classification of major clinical events, such as death and myocardial infarction, was performed by an independent Mortality and Morbidity Classification Committee.
The ACIP study protocol was approved by Institutional Review Committees at each participating site. Written informed consent was obtained from all patients before study entry. An independent Data and Safety Monitoring Board reviewed the safety of treatments as well as protocol adherence and potential protocol changes at 6-month intervals.
Statistical analyses of categorical data were performed using Fisher’s exact test or a χ2 test, and analyses of continuous data were performed using a Student’s t test. The Wilcoxon rank-sum statistic was used for testing the distributions of AECG episodes. The percentage of patients with ischemic ST-segment depression during the initial 10 minutes of the exercise test was estimated using the Kaplan-Meier method12 ; patients who did not complete 10 minutes of exercise for reasons other than ST-segment depression were censored without the event at the time the test was stopped. This analytic method was also used to estimate the time to angina onset and time to onset of ≥1-mm ST-segment depression if the event rate was >50%.
To take into account the many hypotheses tested in the ACIP study, in these secondary analyses P=.01 was regarded as showing some evidence against the null hypothesis, and P=.001 was regarded as strong evidence.
To adjust for discrepancies in demographic factors, presence of risk factors, and clinical differences between the PTCA and CABG groups before treatment,6 multivariable analyses were performed to account for these differences. The following 10 baseline variables were used as adjusting variables in multivariable analyses using the Cox proportional-hazards model13 and in multivariable logistic regression analysis14: age, male sex, angina present, prior MI, diabetes, hypertension, ever smoked, prior revascularization (PTCA or CABG), number of vessels with stenosis ≥50%, and number of ischemic episodes on qualifying AECG.
All data processed in the Clinical Coordinating Center as of January 18, 1995, were included in these analyses.
Performance of Protocol Revascularization
Data reported here are for 558 patients (all 60 patients from one clinical unit have been excluded as reported by Conti et al).15
Of 192 patients assigned to undergo revascularization in the ACIP study, 94 had PTCA attempted, 79 had CABG performed, and 19 did not have any revascularization procedure performed because the patient or treating physician refused after enrollment. Three patients, 2 in the PTCA group and 1 in the CABG group, who had their procedures done after the 12-week visit were excluded from the analysis. Thus, this report is based on 92 patients in whom PTCA was attempted and on 78 patients in whom CABG was performed. The median time interval from study entry to revascularization was 18 days for PTCA and 32 days for CABG.
Multivessel disease was present in 86% of patients undergoing CABG and single-vessel disease in 14%. The average number of grafts was three, and the number of grafts matched or exceeded the number of diseased major coronary arteries in 95% of patients. Internal thoracic artery grafts were used in 85% of patients (one graft in 71% and two grafts in 14%). One patient had another arterial graft.
Multivessel disease was present in 62% of patients undergoing PTCA and single-vessel disease in 38%. By clinical unit assessment, the procedure was successful in 83% of patients. Angiography Core Laboratory assessment of anatomic success was 82% when defined as postangioplasty stenosis <50% for any lesion attempted and 78% for all lesions attempted. One lesion was successfully dilated in 73% of patients, two in 23%, and three in 4%. One vessel was dilated in 89% of patients and two vessels in 11%. Complete revascularization was achieved after PTCA in 32% of patients.
There was no death or myocardial infarction during the 24 hours after CABG. Five patients had other complications: One patient had a stroke followed by recovery with no residual neurological impairment, and four patients were reoperated on for bleeding. Within 24 hours of PTCA, there were three events in two patients: One patient had a nonfatal myocardial infarction and CABG, and another patient had emergency CABG surgery.
At the baseline qualifying visit, patients considered for CABG had more ischemic episodes (median, 5 versus 3; P<.001) and a longer duration of ischemia (median, 28 versus 21 minutes) per 48 hours than patients selected for PTCA (Table 1⇓).
At the 12-week visit, the percentage of patients with no ischemic episodes (primary outcome) was 70% in the CABG patients versus 46% in the PTCA patients (P=.002). The proportion of patients without ischemia on the 48-hour AECG remained practically unchanged at the 6-month (64%), and 12-month (71%) visits in the CABG patients, whereas it increased slightly but not significantly (49% at the 6-month visit and 52% at the 12-month visit) in the PTCA patients (Table 1⇑ and Fig 1⇓).
Mean and maximum heart rates for the 48-hour recording were significantly lower in the PTCA than in the CABG patients, probably because of greater use of heart rate–lowering anti-ischemia medication in these patients (Table 1⇑).
AECG results were available at the qualifying, 12-week, 6-month, and 12-month visits in 100%, 91%, 96%, and 95% of the PTCA patients, respectively, and in 100%, 95%, 99%, and 94% of the CABG patients, respectively (Table 1⇑).
At the qualifying visit, of those selected for CABG there were more patients with ≥1-mm ST-segment depression, more exercise-induced angina, a lower total exercise time, a lower time to 1-mm ST-segment depression, and a lower percentage of age maximum heart rate than patients selected for PTCA (Table 2⇓).
At the 12-week visit, the percentage of patients without ST-segment depression on the ETT was higher in the CABG group than in the PTCA patients (46% versus 23%, P=.005). The percentage of patients without exercise-induced angina was also higher in the CABG than in the PTCA group (90% versus 70%, P=.01). Time to 1-mm ST-segment depression was greater in the CABG than in the PTCA patients (7.6 versus 6.5 minutes, P=.005) and the number of abnormal ECG leads (1.7 versus 3.1, P<.001), the sum of ST-segment depression (3.6 versus 7.0, P<.001), and the maximum depth of ST-segment depression in any lead (0.9 versus 1.7, P<.001) were less in the CABG than in the PTCA patients, respectively. Finally, the percentage of age maximum heart rate was greater in the CABG than in the PTCA patients (93% versus 85%, P<.001). All these differences, except for the incidence of exercise-induced angina, persisted relatively unchanged on the ETTs performed at the 6-month and 12-month visits (Table 2⇑ and Fig 2⇓).
ETT results were available and interpretable at the qualifying, 12-week, 6-month, and 12-month visits in 99%, 91%, 92%, and 90% of the PTCA patients, respectively, and in 99%, 91%, 95%, and 92% of the CABG patients, respectively (Table 2⇑).
Anginal Status and Antianginal Medication Within 4 Weeks
At the qualifying visit, the percentage of patients who were angina-free within 4 weeks before entry was 28% in the CABG patients compared with 42% in the PTCA patients (NS). According to the Canadian Cardiovascular Society classification, angina was class I in 37% versus 24% of patients, respectively; class II in 30% versus 33%, respectively; class III in 5% versus 1%, respectively; and class IV in 0% versus 0%, respectively (Table 3⇓).
At the 12-week visit, 90% of the CABG patients versus 68% of the PTCA patients (P=.001) had not experienced any angina within the previous 4 weeks. In those who were still symptomatic, angina was mild to moderate, Canadian Cardiovascular Society class I or II, in all but one PTCA patient. No patient experienced unstable angina before the 12-week visit. The percentage of patients taking study medication (background or open label to relieve angina) within 4 weeks before the follow-up visit was 10% after CABG versus 49% after PTCA; the percentage of patients taking one drug was 12% versus 36%, respectively, and the percentage taking two drugs was 0% versus 13%, respectively. All these differences remained significant at the 6-month and 12-month visits (Table 3⇑ and Fig 3⇓).
The angina and medication data were available at the qualifying visit in all patients of both revascularization groups, and at the 12-week, 6-month, and 12-month visits in 100%, 100%, and 100% of PTCA patients, respectively, and in 99%, 100%, and 96% of CABG patients, respectively (Table 3⇑).
At 12 weeks, only 1 patient had had a clinical event (myocardial infarction) in the CABG group, whereas 7 patients had had clinical events (3 myocardial infarctions, 2 repeat PTCAs, and 4 CABG surgeries) in the PTCA group. There was no death or additional myocardial infarction in either group during follow-up at 6 and 12 months. A PTCA was performed between 3 and 6 months after study entry in one surgical patient. On the other hand, the number of patients requiring repeat revascularization (PTCA and/or CABG) in the angioplasty group increased from 6 at 84 days to 11 at 183 days and to 15 by 365 days. Overall, the number of clinical events was 1 in the CABG patients versus 12 in the PTCA patients at 183 days (P=.004) and 1 versus 16 at 365 days (P<.001, adjusted P=.006) (Table 4⇓ and Fig 4⇓).
Follow-up for clinical events was 100% complete in both treatment groups through 365 days.
This report describes the 1-year follow-up of patients who were assigned to revascularization in the ACIP trial and extends the observations previously made 12 weeks after randomization.6 The frequency and severity of cardiac ischemia on the 48-hour AECG and on the ACIP protocol ETT and the frequency and severity of angina within the previous 4 weeks were markedly reduced 12 weeks after entry (approximately 8 weeks after randomization) after both PTCA and CABG. However, CABG was more effective than PTCA in suppressing cardiac ischemia and angina at the 12-week visit in the ACIP trial. Cardiac ischemia on the 48-hour AECG, the primary outcome of the study, was eliminated at 12 weeks in 70% of CABG patients versus 46% of PTCA patients, and within 4 weeks of the 12-week visit angina was no longer present in 90% of patients after CABG versus 68% after PTCA. The present report shows that the improvement in angina and ischemia seen at 12 weeks remained significant at the 1-year follow-up visit and that the difference in efficacy between the two procedures also persisted at 1 year. Moreover, the surgical patients had a lower incidence of clinical events at 1 year in the ACIP trial. Clinical events defined as death, nonfatal myocardial infarction, and nonprotocol repeat revascularization were observed at 1 year in only 1 surgical patient compared with 16 angioplasty patients. The incidence of death or myocardial infarction at 1 year was not different in the two treatment groups: 1 event in the surgical patients versus 3 in the angioplasty patients. However, the incidence of repeat revascularization (PTCA or CABG) during the 1-year follow-up period was much higher in the PTCA than in the CABG patients: 15 repeat procedures after the index PTCA versus 1 after the initial CABG.
Previous observational studies have shown that each PTCA or CABG can safely and effectively reduce myocardial ischemia in patients with symptomatic or asymptomatic coronary artery disease.16 17 18 19 20 21 These studies have not clearly established, however, whether ischemia suppression is related to completeness of revascularization18 19 20 and whether ischemia suppression after revascularization influences long-term prognosis.17 19 20
Four randomized trials comparing the efficacy and safety of PTCA versus CABG in the management of patients with symptomatic coronary artery disease have been published recently.22 23 24 25 These trials have shown that, as a rule, the incidence of major coronary events including death and nonfatal myocardial infarction is not different between 1 and 3 years after revascularization among patients assigned to either PTCA or CABG. However, compared with CABG surgery, PTCA is associated with a fourfold to tenfold increase in repeat revascularization during this time period. The design of these trials differs from the ACIP protocol in several respects. Except for the Randomized Intervention Treatment of Angina (RITA) trial in which approximately one half of the patients had single-vessel disease,22 all the other trials were performed in patients with multivessel coronary disease. In the four trials, the patients were randomly assigned to either PTCA or CABG and thus had to present angiographic lesions that were suitable for both procedures. In the ACIP trial, the patients had to have angiographic lesions that were suitable for either PTCA or CABG; they were randomly assigned to revascularization, and the choice of the procedure, PTCA or CABG, was made by the physician and patient, based on the angiographic results. Thus, the ACIP protocol captured a much greater patient population. Yet, the clinical outcome at 1 year after revascularization by PTCA or CABG in the ACIP trial was similar to that of these other trials.
A reduction in mortality for up to 10 years after CABG, compared with medical management, in medium-risk and high-risk patients with stable coronary artery disease has been documented in several previous trials.26 There is also evidence suggesting that, in patients with triple-vessel disease and patients with double-vessel disease in whom a critical lesion of the left anterior descending artery is present, 5-year survival is greater after CABG surgery than after PTCA.27 In view of the current evidence that cardiac ischemia is associated with an increased risk of adverse clinical outcome1 2 3 4 and that revascularization, and in particular CABG surgery, offers the best strategy to eliminate cardiac ischemia,5 a long-term trial evaluating the effect of ischemia suppression on clinical outcome using the ACIP protocol is warranted.
The present study has several limitations. First, the revascularization procedure was not randomly assigned. However, we feel that the ACIP study design where the choice of PTCA or CABG was determined by the physician and patient corresponds closely to the usual pattern of routine clinical practice. Second, the degree of revascularization achieved by PTCA and CABG was not ascertained by a follow-up coronary angiogram relatively late (1 year) after revascularization. This information would have been very helpful to correlate the reduction of ischemia with completeness of revascularization in both procedures. Finally, the number of events in both treatment groups is too small to allow any definitive conclusions, and the effect of ischemia suppression after revascularization on clinical outcome will require a much larger and more long-term mortality trial.
Selected Abbreviations and Acronyms
|ACIP||=||Asymptomatic Cardiac Ischemia Pilot|
|CABG||=||coronary artery bypass graft|
|ETT||=||exercise treadmill test|
|PTCA||=||percutaneous transluminal coronary angioplasty|
The present study was funded by the National Heart, Lung, and Blood Institute, Cardiac Diseases Branch, Division of Heart and Vascular Diseases, Bethesda, Md, by research contracts HV-90-07, HV-90-08, and HV-91-05 through HV-91-14. Study medications and placebo were donated by Zeneca Pharma Inc, Marion-Merrell Dow, and Pfizer. Support for ECG data collection was provided in part by Applied Cardiac Systems, Marquette Electronics, Mortara Instrument Incorporated, and Quinton Instruments.
Reprint requests to ACIP Clinical Coordinating Center, Maryland Medical Research Institute, 600 Wyndhurst Ave, Baltimore, MD 21210.
↵1 A list of participating centers and investigators is included in “Asymptomatic Cardiac Ischemia Pilot (ACIP) Study: Outcome at One Year for Patients With Asymptomatic Cardiac Ischemia Randomized to Medical Therapy or Revascularization,” J Am Coll Cardiol (in press).
- Copyright © 1995 by American Heart Association
Bonow RO, Bacharach SL, Green MV, La Freniere RL, Epstein SE. Prognostic implications of symptomatic versus asymptomatic (silent) myocardial ischemia induced by exercise in mildly symptomatic and in asymptomatic patients with angiographically documented coronary artery disease. Am J Cardiol. 1987;60:778-783.
Deedwania PC, Carbajal EV. Silent ischemia during daily life is an independent predictor of mortality in stable angina. Circulation. 1990;81:748-756.
Yeung AC, Barry J, Orav J, Bonassin E, Raby KE, Selwyn AP. Effects of asymptomatic ischemia on long-term prognosis in chronic stable coronary disease. Circulation. 1991;83:1598-1604.
Knatterud GL, Bourassa MG, Pepine CJ, Geller NL, Sopko G, Chaitman BR, Pratt C, Stone PH, Davies RF, Rogers WJ, Deanfield JE, Goldberg AD, Ouyang P, Mueller H, Sharaf B, Day P, Selwyn AP, Conti CR, for the ACIP Investigators. Effects of treatment strategies to suppress ischemia in patients with coronary artery disease: 12-week results of the Asymptomatic Cardiac Ischemia Pilot (ACIP) study. J Am Coll Cardiol. 1994;24:11-20.
Bourassa MG, Pepine CJ, Forman SA, Rogers WJ, Dyrda I, Stone PH, Chaitman BR, Sharaf B, Mahmarian J, Davies RF, Knatterud GL, Terrin M, Sopko G, Conti R, for the ACIP Investigators. Asymptomatic Cardiac Ischemia Pilot (ACIP) study: effects of coronary angioplasty and coronary artery bypass graft surgery on recurrent angina and ischemia. J Am Coll Cardiol. 1995;26:606-614.
Pepine CJ, Geller NL, Knatterud GL, Bourassa MG, Chaitman BR, Davies RF, Day P, Deanfield JE, Goldberg AD, McMahon RP, Mueller H, Ouyang P, Pratt C, Proschan M, Rogers WJ, Selwyn AP, Sharaf B, Sopko G, Stone PH, Conti CR, for the ACIP Investigators. The Asymptomatic Cardiac Ischemia Pilot (ACIP) study: design of a randomized clinical trial, baseline data, and implications for a long-term outcome trial. J Am Coll Cardiol. 1994;24:1-10.
Kirklin JW, Akins CW, Blackstone EH, Booth DC, Califf RM, Cohen LS, Hall RJ, Harrell FE, Kouchoukos NT, McCallister BD, Naftel DC, Parker JO, Sheldon WC, Smith HC, Wechsler AS, Williams JF. Guidelines and indications for coronary artery bypass graft surgery: a report of the American College of Cardiology/American Heart Association task force on assessment of diagnostic and therapeutic cardiovascular procedures. J Am Coll Cardiol. 1991;17:543-589.
Ryan TJ, Faxon DP, Gunnar RM, Kennedy JW, King SB, Loop FD, Peterson KL, Reeves TJ, Williams DO, Winters WL. Guidelines for percutaneous transluminal coronary angioplasty: a report of the ACC/AHA task force on assessment of diagnostic and therapeutic cardiovascular procedures. J Am Coll Cardiol. 1988;12:529-545.
Bourassa MG, Alderman EL, Bertrand M, de la Fuente L, Gratsianski A, Kaltenbach M, King SB, Nobuyoshi M, Romaniuk P, Ryan TJ, Serruys PW, Smith HC, Sousa E, Böthig S, Rapaport E. Report of the joint ISFC/WHO task force on coronary angioplasty. Circulation. 1988;78:780-789.
Cox DR. Regression models and life tables (with discussion). J R Stat Soc B. 1972;34:187-220.
Hosner DW, Leneshow S. Applied Logistic Regression. New York, NY: John Wiley & Sons; 1989:106-118.
Conti CR, Knatterud GL, Sopko G. Erratum. J Am Coll Cardiol. 1995;26:842.
Crea F, Kaski JC, Fragasso G, Hackett D, Stanbridge R, Taylor KM, Maseri A. Usefulness of Holter monitoring to improve the sensitivity of exercise testing in determining the degree of myocardial revascularization after coronary artery bypass grafting for stable angina pectoris. Am J Cardiol. 1987;60:40-43.
Kennedy HL, Seiler SM, Sprague MK, Homan SM, Whitlock JA, Kern MJ, Vandormael MG, Barner HB, Codd JE, Willman VL. Relation of silent myocardial ischemia after coronary artery bypass grafting to angiographic completeness of revascularization and long-term prognosis. Am J Cardiol. 1990;65:14-22.
Weiner DA, Ryan TJ, Parsons L, Fisher LD, Chaitman BR, Sheffield LT, Tristani FE. Prevalence and prognostic significance of silent and symptomatic ischemia after coronary bypass surgery: a report from the Coronary Artery Surgery Study (CASS) randomized population. J Am Coll Cardiol. 1991;18:343-348.
Rodriguez A, Boullon F, Perez-Baliño N, Paviotti C, Sosa Liprandi MI, Palacios IF, on behalf of the ERACI group. Argentine randomized trial of percutaneous transluminal coronary angioplasty versus coronary artery bypass surgery in multivessel disease (ERACI): in-hospital results and 1-year follow-up. J Am Coll Cardiol. 1993;22:1060-1067.
Hamm CW, Reimers J, Ischinger T, Rupprecht H-J, Berger J, Bleifeld W, for the German Angioplasty Bypass Surgery Investigation. A randomized study of coronary angioplasty compared with bypass surgery in patients with symptomatic multivessel coronary disease. N Engl J Med. 1994;331:1037-1043.
Yusuf S, Zucker D, Peduzzi P, Fisher LD, Takaro T, Kennedy JW, Davis K, Killip T, Passamani E, Norris R, Morris C, Mathur V, Varnauskas E, Chalmers TC. Effect of coronary artery bypass graft surgery on survival: overview of 10-year results from randomized trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. Lancet. 1994;344:563-570.
Mark DB, Nelson CL, Califf RM, Harrel FE, Lee KL, Jones RH, Fortin DF, Stack RS, Glower DD, Smith LR. Continuing evolution of therapy for coronary artery disease: initial results from the era of coronary angioplasty. Circulation. 1994;89:2015-2025.