Author + information
- Received September 25, 1996
- Revision received February 10, 1997
- Accepted February 26, 1997
- Published online June 1, 1997.
- Edward D. Folland, MD, FACCA,*,
- Pamela M. Hartigan, PhDB,
- Alfred F. Parisi, MD, FACCC,
- for the Veterans Affairs ACME Investigators1
- ↵*Dr. Edward D. Folland, Cardiology Section, Memorial Hospital, 119 Belmont Street, Worcester, Massachusetts 01605.
Objectives. This study sought to assess outcomes of men with double-vessel coronary artery disease randomly assigned to treatment by percutaneous transluminal coronary angioplasty (PTCA) or medical therapy, compared with previously reported outcomes for men with single-vessel disease.
Background. We previously reported that PTCA provides better symptom relief and treadmill performance than medical therapy for men with stable angina pectoris due to single-vessel disease. Whether this advantage applies to patients with double-vessel disease is unknown.
Methods. Male patients (n = 328) with stable angina pectoris and ischemia on treadmill testing were randomly assigned to PTCA or medical therapy; 101 patients had double-vessel disease, and 227 had single-vessel disease. Symptoms, treadmill performance, quality of life score, coronary stenosis and myocardial perfusion were compared at baseline and at 6 months. Patients were followed up for up to 6 years and underwent additional treadmill testing 2 to 3 years after randomization.
Results. PTCA-treated and medically treated patients with double-vessel disease experienced comparable improvement in exercise duration (+1.2 vs. +1.3 min, respectively, p = 0.89), freedom from angina (53% and 36%, respectively, p = 0.09) and improvement of overall quality of life score (+1.3 vs. +4.4, respectively, p = 0.32) at 6 months compared with baseline. This contrasts with greater advantages favoring PTCA by these criteria in patients with single-vessel disease (p = 0.0001 to 0.02). Trends present at 6 months persisted at late follow-up. Patients undergoing double-vessel dilation had less complete initial revascularization (45% vs. 83%) and greater average stenosis of worst lesions at 6 months (74% vs. 56%). Likewise, patients with double-vessel disease showed less improved myocardial perfusion imaging (59% vs. 75%).
Conclusions. PTCA is beneficial in male patients with double-vessel disease; however, we cannot demonstrate the same advantage over medical therapy seen in similar patients with single-vessel disease. Less complete revascularization and greater restenosis for patients having multiple dilations would account for these findings. Alternatively, a type 2 error might be operative. Technical advances since completion of this trial might improve these outcomes. These findings warrant further investigation in a larger trial.
(J Am Coll Cardiol 1997;29:1505–11)
In previous reports ([1, 2]) we showed that percutaneous transluminal coronary angioplasty (PTCA) results in earlier and more complete relief from angina pectoris, greater improvement in exercise performance and better quality of life at 6-month follow-up compared with medical therapy for 212 men with stable single-vessel coronary artery disease. Whether this same advantage of PTCA over medical treatment is present for patients with double-vessel coronary artery disease and chronic stable angina has not yet been demonstrated. There are reasons to suspect that the relative advantage of PTCA may be less in patients with more complex disease. As the number of vessels treated increases, it is anticipated that the chance of initially incomplete revascularization or subsequent restenosis of at least one vessel increases, making it more likely that PTCA by itself will fail to completely relieve manifestations of myocardial ischemia.
We present herein the results of a pilot study comparing the previously unreported clinical outcomes of clinically stable patients with double-vessel coronary artery disease who were randomly assigned to a strategy of initial treatment by PTCA or optimal medical therapy. We then contrast these results with the previously reported results for patients with single-vessel disease. Although our study was primarily intended to address patients with single-vessel disease, patients with double-vessel disease were deliberately and prospectively recruited as long as patients with single-vessel disease were being entered. Sample size, power and the related choice of number of study sites and length of intake were all based on expected outcomes and accrual rates for patients with single-vessel disease. We chose to include patients with double-vessel disease because at the time that our study was planned, PTCA was a growing but controversial treatment for patients with multivessel coronary artery disease (). Given the frequency at which multivessel PTCA was performed at that time, we would have required many more study sites and a much longer duration of intake to achieve statistical power comparable to our cohort with single-vessel disease. Nevertheless, we chose to randomize and study patients with double-vessel disease using the same protocol developed for patients with single-vessel disease; despite the sample size limitations, we judged that even limited information, if randomized, would be useful.
1.1 Patient Selection
Patients screened for the study included all those who underwent diagnostic coronary angiography for a primary diagnosis of coronary artery disease at the participating centers (). Patients having had coronary angiography elsewhere but who were referred to one of the study centers for PTCA were also screened. Clinical, angiographic and exercise test criteria were required for entry into the study. Clinical requirements were either a history of angina, an acute myocardial infarction within 3 months or ≥3 mm horizontal ST segment depression on an exercise electrocardiogram (ECG). The major clinical exclusions were medically refractory unstable angina, previous coronary artery revascularization and primary cardiac diagnosis other than coronary artery disease. Angiographic requirements were at least 70% diameter stenosis in the proximal two-thirds of one or two major coronary arteries. The lesions in at least one of the arteries had to be technically amenable to PTCA, and all patients were required to be suitable candidates for potential coronary artery bypass graft surgery in case of abrupt closure during angioplasty. Patients were excluded for left main coronary artery stenosis ≥50%, ≥70% stenosis of more than two major coronary arteries (three-vessel disease) or a left ventricular ejection fraction ≤30%. By necessity, these criteria were based on measurements made by local investigators, not core laboratories. Once enrolled, patients were not excluded if core laboratory readings differed from local measurements.
1.2 Randomization Criteria
Patients who met clinical and angiographic entry criteria and granted written informed consent for the study underwent baseline exercise tolerance testing using the modified Bruce treadmill protocol () with thallium-201 myocardial imaging at least 24 h after being weaned off all antianginal medications. Those patients meeting the following exercise test inclusion criteria were enrolled in the study: 1) at least 1-mm horizontal or downsloping ST segment depression with exercise; or, in the absence of ST segment depression, 2) exercise-induced angina with a reperfusing thallium-201 image defect at the location of the patient’s arterial disease. Qualifying patients were then randomly assigned to either PTCA or medical treatment according to the following randomization strata: group 1a= single-vessel disease, ≤99% stenosis; group 1b= single-vessel disease, 100% occlusion; group 2a= double-vessel disease, both vessels amenable to PTCA; and group 2b= double-vessel disease, only one vessel amenable to PTCA.
1.3 Patient Treatment
Patients assigned to PTCA treatment were given aspirin and calcium channel blocking agent therapy and underwent dilation as soon as possible (usually within 72 h of randomization). They returned to the clinic for five monthly assessments of angina and nitroglycerin use and to the hospital at 6 months for clinical assessment, a follow-up thallium-201 exercise tolerance test and a follow-up coronary angiogram. PTCA-assigned patients were weaned off any antianginal medication 24 h before the follow-up exercise test, so that the only variable between baseline and follow-up exercise testing was coronary intervention. Patients who experienced recurrent angina during follow-up were, if necessary, urged to undergo repeat angiography and treated aggressively with repeat PTCA for restenosis.
Participating centers and study interventionalists were selected with the assistance of a nationally recognized independent expert on PTCA who reviewed study proposals and PTCA case records from prospective centers (). All study PTCAs were performed by experienced staff interventionalists certified by independent review to meet minimal standards of safety, volume and success. Study interventionalists were required to have performed a minimum of 100 PTCAs independently since training.
Patients assigned to medical treatment received aspirin plus individualized therapy utilizing nitrates, beta-adrenergic blocking agents and calcium channel blockers in a progressive, stepped-care approach similar to usual clinical practice for treatment of angina. Drug doses were increased and additional agents added during monthly visits to the clinic, with the goal of complete suppression of angina with minimal medication side effects. At 6 months, these patients returned to the hospital for follow-up thallium-201 exercise tolerance testing and repeat coronary angiography. Medically assigned patients received follow-up exercise testing while receiving their individually optimized medical treatment so that the effect of this treatment on exercise performance could be compared with the untreated baseline state.
1.4 Core Laboratories
All coronary angiograms, exercise ECGs and thallium-201 images were read in blinded manner by observers in central laboratories. Coronary angiograms were evaluated by hand-held electronic calipers, a technique that has been validated as comparable to computer methods in this study cohort (). Exercise thallium-201 images were scored by a standard method in the core laboratory at Massachusetts General Hospital ([6, 7]). Three segments from each of three views were graded as 0, 1 or 2 for absent, reduced or normal uptake, respectively. Points for all segments were totaled for a maximal score of 18. Changes in myocardial perfusion were assessed by comparing the stress image scores at baseline and at 6 months.
1.5 Quality of Life Assessment
A two-part, self administered quality of life questionnaire was administered to all patients at baseline and at 6 months after randomization. This test consisted of 11 questions that measured physical functioning and 22 questions that measured psychological well-being. The answers were summed to yield an overall score, with higher scores reflecting more favorable quality of life. Details of this test and its validation have been previously published ().
1.6 Myocardial Infarction
Myocardial infarction was defined as the appearance of new Q wave (≥0.04-s duration or ≥25% total QRS voltage) in any anterior or lateral lead or in two or more contiguous inferior leads on a follow-up ECG or hospital admission for chest pain accompanied by serum enzyme changes meeting local hospital criteria for myocardial infarction. Procedural myocardial infarction was defined likewise. Peak creatinine kinase (CK) levels were reported when available for patients experiencing acute myocardial infarction.
1.7 Late Follow-Up
Patients were followed up by mailed questionnaire or telephone call, or both, for up to 6 years to account for the following events: PTCA, coronary artery bypass graft surgery, hospital admission, acute myocardial infarction and death. In addition, whenever possible, patients underwent an additional exercise tolerance test at 2 to 3 years after randomization. This test was similar to the baseline and 6-month test, except that medications were not stopped for PTCA-assigned patients, and thallium-201 perfusion imaging was not required.
1.8 Outcome Analysis
Outcomes were expressed as mean changes from baseline to follow-up, with each patient serving as his own control. Clinical outcomesincluded changes in angina frequency during each 30-day follow-up time period compared with baseline values (30 days before randomization) and the percent of patients free from angina during the last month of follow-up compared with that at baseline month. Exercise outcomesincluded changes in total duration of exercise, time to onset of angina and maximal rate–pressure product (systolic pressure [mm Hg] times heart rate [beats/min]). Angiographic outcomewas the change in mean percent diameter stenosis of the index lesions from baseline to the follow-up angiogram. Index lesionswere defined as any stenosis considered a target for PTCA treatment. Hence, some patients with single-vessel disease (randomization groups 1a and 1b) may have more than one index lesion due to serial stenoses or side branch lesions, and some patients with double-vessel disease (randomization group 2b) may have only one index lesion because the second lesion is a chronic total occlusion and not considered a treatment target. The treatment of myocardial perfusion and quality of life outcomes was presented earlier.
1.9 Statistical Methods
The two groups were compared by the chi-square test or Fisher exact test for discrete variables and the ttest or Wilcoxon rank sum test for continuous variables (). Time to onset of ST depression or angina on the treadmill was analyzed using time to failure methods, and the treatments were compared using the log-rank statistic (). All reported p values are two-tailed, and all analyses were performed according to an intention to treat principle.
2.1 Patient Characteristics
Of 9,398 patients screened, 523 were eligible, and 328 granted written informed consent for the study. The leading reasons for exclusion were ongoing unstable angina, three-vessel or left main coronary artery disease and previous revascularization (). Two hundred twelve patients were randomized in group 1a (single-vessel disease, ≤99% stenosis) (), 15 in group 1b (single-vessel disease, total occlusion), 64 in group 2a (double-vessel disease, both amenable to PTCA) and 37 in group 2b (double-vessel disease, only one amenable to PTCA). Baseline characteristics were comparable between patients assigned to PTCA and medical therapy within all randomization strata. However, some differences were noted between randomization strata (Table 1). There were significantly more index lesions per patient in group 2a (2.2 lesions/patient) compared with group 2b (1.4 lesions/patient, in which case the second diseased vessel was considered untreatable by PTCA and therefore was not counted as an index lesion). The second diseased vessel in group 2b was chronically occluded in 29 (78%) of 37 patients. As expected, previous myocardial infarction was more prevalent in this group (57%) than in groups 2a (38%) and 1a (31%). The average number of index lesions in group 1a was 1.2 because of serial or branch lesions in the same coronary vessel (16 patients). Because of the small number of patients in stratum 1b (n = 15), this group was combined with group 1a hereinafter for statistical analysis.
2.2 Treatment Received
Fifty-one patients with double-vessel disease were assigned to PTCA, and all underwent the procedure. Five patients with single-vessel disease assigned to PTCA did not undergo the procedure because of patient refusal or spontaneous regression of the index lesion (Table 2). Repeat PTCA was required in 11 of 51 PTCA-assigned patients with double-vessel disease and 17 of 115 PTCA-assigned patients with single-vessel disease. Emergency coronary artery bypass graft surgery due to abrupt vessel closure was required in 3 of 161 patients who underwent PTCA. By 6 months after randomization, a total of 10 PTCA-assigned patients with either single- or double-vessel disease had undergone coronary artery bypass graft surgery in contrast to only one patient assigned to medical treatment. At 6 months, ∼50% of all patients assigned to PTCA were receiving some antianginal medication: 55 of 103 patients with single-vessel disease and 25 of 45 patients with double-vessel disease.
2.3 Adverse Events
The occurrence of myocardial infarction and death was not different between patients assigned to PTCA and medical therapy by 6 months (Table 3). Although the likelihood of myocardial infarction was approximately twice as great for patients with double-vessel disease (8 of 101 patients) versus single-vessel disease (8 of 227 patients) during the first 6 months (p = 0.09), the incidence was similar over the entire period of follow-up (12% vs. 10%, respectively). Among patients with double-vessel disease at 6 months, two procedure-related (PTCA) myocardial infarctions occurred, one in each treatment arm. Both were nonfatal (non–Q wave, maximal CK 173 and 930 U, respectively). Among patients with single-vessel disease at 6 months, there were four procedure-related (PTCA) infarctions, all nonfatal. One of these was a Q wave infarction (maximal CK 1,515 U); the other three were non–Q wave infarctions, with maximal CK values of 264, 540 and 830 U, respectively. Among all patients there were 15 cases of abrupt closure not requiring coronary artery bypass graft surgery; 7 occlusions were reopened successfully by repeat PTCA; and 6 were treated medically.
2.4 Exercise, Symptom and Quality of Life Outcomes
Paired exercise tolerance tests (baseline and 6 month) were available for 87 patients with double-vessel disease (43 PTCA group, 44 medical group) and 213 with single-vessel disease (109 PTCA group, 104 medical group). For patients with double-vessel disease, both treatment groups experienced comparable improvement in exercise duration and time to onset of angina (if any) (Table 4). The maximal rate–pressure product increased by 1,300 mm Hg × beats/min in the PTCA group and decreased by 2,600 mm Hg × beats/min in the medical group (p = 0.005).
Paired symptom questionnaires (baseline and 6 month) were available for 90 patients with double-vessel disease (45 PTCA group, 45 medical group) and 210 with single-vessel disease (103 PTCA group, 107 medical group). For patients with double-vessel disease, there was a nonsignificant trend toward greater freedom from angina during the sixth month in the PTCA group (53%) than in the medical group (36%, p = 0.09). Reduction in the frequency of angina during the last month was comparable (Table 4). In contrast, patients with single-vessel disease had significantly greater freedom from angina and reduction of angina frequency in the PTCA group than the medical treatment group. The results for single-vessel disease (group 1a) have been previously reported in detail () and are recapitulated, including group 1b, for comparison in Table 4.
Paired quality of life questionnaires (baseline and 6 month) were available for 72 patients with double-vessel disease (35 PTCA group, 37 medical group) and 195 with single-vessel disease (95 PTCA group, 100 medical group). Mean scores improved for both treatment groups with double-vessel disease. Although the improvement was greater for the medical treatment group (+4.4 vs. +1.3), the difference was not significant (p = 0.32). In contrast, patients with single-vessel disease experienced significantly greater (p = 0.01) improvement with PTCA (+7.1) than with medical treatment (+1.5).
2.5 Angiographic Outcomes
Complete initial angiographic success as defined by at least 20% reduction of stenosis of all index lesions was 45% in group 2a, 80% in group 2b, 82% in group 1a and 70% in group 1b.
A patient’s tendency for ischemia can be characterized by his worst (most severe) lesion. In Table 5the worst index lesions of patients in each stratum are averaged before, immediately after and 6 months after PTCA. The second diseased vessel in group 2b (usually chronically occluded) was not a treatment target and is not included in this analysis. In group 2a the average of worst lesions falls from 86% at baseline to 49% immediately after PTCA but rebounds to 74% at 6-month follow-up. The extent of rebound at 6 months compared with that immediately after PTCA is less in groups 2b and 1a (30% to 50% and 40% to 56%, respectively) than in group 2a. The number of index lesions treated is less in groups 2b and 1a (1.4 and 1.2 lesions/patient, respectively) than in group 2a (2.2 lesions/patient). If the average of all index lesions is calculated, a similar pattern emerges as seen in Table 5.
2.6 Myocardial Perfusion Outcomes
Myocardial perfusion imaging with thallium-201 provides an additional, independent means of measuring the effect of PTCA compared with medical treatment. Table 6displays the numbers of patients whose exercise perfusion image scores improved, remained unchanged or worsened in each treatment group and randomization stratum. All medically treated patients are combined because the distribution of changes in the four medical treatment strata was similar. In the combined medical treatment group, 51% improved, 27% were unchanged, and 22% were worse. Patients with single-vessel disease treated by PTCA had significantly (p = 0.003) more improvement (77%) and less worsening (9%) than those treated by medical therapy. Patients with double-vessel disease in both PTCA treatment strata (groups 2a and 2b) displayed distributions of perfusion image changes that were not statistically different from those of medically treated patients, although patients in group 2a showed a trend toward more scintigraphic improvement than those in group 2b.
2.7 Late Follow-up of Patients With Double-Vessel Disease
Late (≥3-year) follow-up questionnaire data were available for 76 patients (75% of possible) with double-vessel disease (39 PTCA, 37 medical). At a median follow-up of 60 months (up to 95 months), 20 medically assigned patients were receiving medication alone, and 20 had undergone PTCA and 15 coronary artery bypass graft surgery. Twenty-five PTCA-assigned patients had undergone repeat PTCA, and 16 underwent coronary bypass. There were no differences between the medical and PTCA treatment groups in number of patients experiencing myocardial infarction (6 medical, 6 PTCA) and deaths (9 medical, 10 PTCA). In patients with double-vessel disease, the nonsignificant trend favoring greater freedom from angina at 6 months for PTCA treatment persisted at 1, 2, 3 and 4 years of follow-up (67.3% vs. 36.0% [n = 99], 63.6% vs. 32.3% [n = 64], 62.9% vs. 36.4% [n = 68], 59.4% vs. 48.1% [n = 59], respectively). Fifty-eight patients (27 PTCA, 31 medical) had late exercise tolerance tests at 2 to 3 years after randomization. Improvements in exercise duration were still comparable for PTCA- and medically treated patients compared with baseline values (0.85 and 0.50 min, respectively); however, the extent of improvement had decreased for both groups compared to the 6-month follow-up test values. Changes in maximal rate–pressure product at 2- to 3-year testing compared with baseline values were still in the same direction (+1,105 mm Hg × beats/min for PTCA, −1,273 mm Hg × beats/min for medicine) but were no longer significantly different (p = 0.14).
3.1 Implications for Future Trials
In this study of clinically stable male patients with two-vessel coronary artery disease, comparable decrease in symptoms and improvement in exercise performance at 6 months were demonstrated regardless of initial treatment strategy of PTCA or medication. This improvement persisted at late follow-up. Because this represents a pilot study run in parallel with a larger trial that addressed single-vessel coronary artery disease, it is statistically underpowered to detect small differences in outcome between treatment groups. Nevertheless, if any such differences do exist, they are likely to be smaller than the significant advantages demonstrated for PTCA in men with single-vessel disease. To our knowledge, our trial provides the only data available to date on this subject. These trends are provocative and suggest the need for a larger study, such as the Randomized Intervention Treatment of Angina (RITA)-2 trial now in progress, which, among other issues, will address PTCA versus medical treatment for double-vessel disease. Based on our experience, such a trial would require 500 to 750 patients. For instance, to demonstrate a difference in freedom from angina of 45% versus 30% for PTCA and medical treatment groups, respectively, at p value ≤0.05 with 90% power would require 220 patients in each treatment group. To demonstrate a 1-min difference in exercise duration with a standard deviation of 2.8 min at p ≤ 0.05, 90% power, would require 330 patients in each group. Anticipating a 10% loss of follow-up, it would be necessary to enroll 363 patients in each group, for a total sample of 726 patients.
3.2 Anatomic Basis for Clinical Outcomes
Our data provide two explanations for the apparent smaller advantage of PTCA over medical treatment in men with double-vessel disease than in similar patients with single-vessel disease: First, the initial likelihood of complete revascularization decreases as the number of diseased vessels increases. This is especially so for patients in whom the second diseased vessel is chronically occluded and hence not a target for intervention (group 2b), but is also the case for group 2a in which both diseased vessels were targets for intervention. As the average number of PTCA targets (index lesions) rises from 1.2/patient in the single-vessel disease groups to 2.2/patient in group 2a, the rate of complete initial success falls from 82% to 45%.
These angiographic results compare favorably with contemporaneous performance standards during the time period when patients were entered into our study (1987 to 1990), especially in light of the fact that they were based on objective criteria from quantitative angiography interpreted in blinded manner ([10, 11]). Our minimal criterion for successful intervention (reduction ≥20% diameter stenosis) is validated by an intraobserver variability study of a subset of angiograms read twice in which two standard deviations of the mean variability of blinded caliper readings was 18.8% (). Absolute success rates are higher in 1997 due to improvements in balloon and guiding catheter design as well as alternative endovascular techniques; nevertheless, the principle of decreasing likelihood of complete success with increasing number of targets should remain.
A second explanation for less advantage of PTCA in double compared with single-vessel disease is that the chance of restenosis of at least one vessel increases as the number of vessels dilated increases. This is supported by the fact that the average percent stenosis of the worst index lesions at 6 months is greater for men with multiple index lesions (74% in group 2a) than men with fewer index lesions (56% in group 1a; 50% in group 2b) despite all three groups having comparable average worst index lesion stenosis immediately after PTCA (49% in group 2a, 40% in group 1a, 30% in group 2b) (Table 5). The same pattern is also evident for the average stenosis of all index lesions at 6 months. Group 1b demonstrates greater restenosis, as would be expected for totally occluded index lesions. In addition, the improvement in thallium-201 stress image score at 6 months was significantly better for PTCA than medical therapy only for patients with single-vessel disease (Table 6). This provides independent physiologic confirmation of the anatomic evidence from angiography.
3.3 Comparison of Physiologic Benefits of PTCA and Medical Therapy
The changes in maximal rate–pressure product from baseline to 6 months were significantly different and consistent with the known physiologic mechanisms of benefit from PTCA and medical therapy. Patients treated by PTCA experienced increased freedom from ischemia and were able to achieve higher maximal rate–pressure product (+1,300 mm Hg × beats/min). Patients treated by medical therapy experienced increased freedom from ischemia by pharmacologic reduction of maximal rate–pressure product (−2,600 mm Hg × beats/min). Hence, PTCA raised ischemic threshold by improving myocardial oxygen supply, whereas medical therapy raised ischemic threshold by reducing myocardial oxygen demand. These trends were still present at the 2- to 3-year follow-up exercise test (+1,105 mm Hg × beats/min for PTCA, −1,273 mm Hg × beats/min for medicine) despite the fact that medications were not stopped for PTCA-treated patients for this test, and many of the medically assigned patients had undergone intervention. Statistical significance was no longer achievable for this difference because of the reduced number of patients (n = 58) completing the late test. If concurrent medical therapy had been allowed at the time of the 6-month follow-up stress test, greater advantages of PTCA over medical treatment might have been demonstrated. However, it was our intention to compare medical treatment with unaided revascularization as much as possible, even though the two modalities are often combined in clinical practice.
This pilot study suggests that the symptom, quality of life and exercise performance advantages of PTCA over medical therapy demonstrated in the Angioplasty Compared to Medicine (ACME) study of men with single-vessel disease may be relatively diminished for patients with double-vessel disease. One hundred one men with double-vessel disease experienced comparable improvement with both treatments, although the study was underpowered to detect small differences. The relative advantage of PTCA over medical treatment may be diminished by the reduced likelihood of complete revascularization and the increased likelihood of restenosis in men with multiple treatment targets. Although a type 2 error may be operative in the double-vessel disease group, these findings are provocative and constitute a data base that justifies funding of larger trials.
We acknowledge Elizabeth Brosnihan for assistance in preparation of the manuscript.
It was presented in part at the 64th Annual Scientific Sessions of the American Heart Association, Anaheim, California, November 1991.
↵fn1 This study was supported by the Cooperative Studies Program (study no. 267) of the U.S. Department of Veterans Affairs, Washington, D.C.
- creatine kinase
- percutaneous transluminal coronary angioplasty
- Received September 25, 1996.
- Revision received February 10, 1997.
- Accepted February 26, 1997.
- The American College of Cardiology
- the Veterans Affairs ACME Investigators,
- Strauss WE,
- Fortin T,
- Hartigan P,
- Folland ED,
- Parisi AF
- for the Veterans Affairs ACME Investigators,
- Folland ED,
- Vogel RA,
- Hartigan P,
- et al.
- Snedecor GW,
- Cochran WG
- for the Co-Investigators of the National Heart, Lung and Blood Institute’s Percutaneous Transluminal Angioplasty Registry,
- Detre K,
- Holubkov R,
- Kelsey S,
- et al.
- for the Co-Investigators of the National Heart, Lung and Blood Institute’s Percutaneous Transluminal Coronary Angioplasty Registry,
- Detre KM,
- Holmes DR,
- Holubkov R,
- et al.