Review of the ACME trial
Angioplasty versus medical therapy in stable coronary artery disease
Background: Revascularization with coronary artery bypass surgery improves symptoms in patients with chronic stable angina as seen in the European Coronary Surgery Study. Percutaneous transluminal coronary angioplasty (PTCA) is less invasive compared to surgery and is associated with less mortality and morbidity. Consequently, its use increased significantly in the late 1980s and early 1990s, driven by its perceived benefits over medical therapy alone due to the ability of PTCA to reduce coronary artery luminal stenosis.
The Angioplasty Compared to Medicine (ACME) study sought to test the hypothesis that PTCA improves symptoms in patients with single vessel sable coronary artery disease.
Patients: Eligible patients were recruited from Veterans Affairs centers. Patients had to have 70 – 99% stenosis in the proximal two thirds of one major epicardial coronary artery plus one of the following: stable angina pectoris, very positive exercise-tolerance test (ST-segment depression ≥3 mm) or a myocardial infarction within the past 3 months.
Baseline characteristics: The study screened 9,573 patients and among them only 212 (2.2%) were enrolled – 107 randomized to medical therapy and 105 to PTCA. The reasons for patients’ exclusion were provided in table 1 of the manuscript. Some key exclusion criteria were previous CABG, unstable angina, prior PTCA, 3-vessel disease or lesions not suitable for PTCA.
The average age of enrolled patients was 63 years. Approximately 30% had prior myocardial infarction, 53% had hypertension, 18% had diabetes, 1% had congestive heart failure, and 31% were current smokers. There were more employed participants in the PTCA arm 42% vs 29%. The average systolic blood pressure was 136 mm Hg. The average total cholesterol was 230 mg/dl.
The average duration participants did on the treadmill was 8.8 minutes. Approximately 38% had LAD disease, 25% had LCx disease, and 37% had RCA disease.
Procedures: All patients were admitted to the hospital. Anti-anginal medications were stopped for at least 24 hours and exercise stress test that included thallium Scintigraphy was performed. The test was considered positive if there was horizontal or down-sloping ST-segment depression ≥ 1.0 mm in one or more leads measured 80 msec after the J point that occurred during or after treadmill exercise testing. Patients who had angina during the test but did not meet the above criteria could be included if there was evidence on thallium scanning of a reversible defect in the area corresponding to the index lesion. If the test showed ischemia, patients were then assigned to PTCA or medical therapy.
All patients received aspirin 325 mg/day. Patients in the medical arm received one or combination of the following: nitrates, beta-blockers or calcium channel blockers. Patients in the PTCA arm received calcium channel blockers before and for one month after the procedure, and nitroglycerin during and for 12 hours after the procedure.
Patients were followed monthly. Patients were admitted to the hospital 6 months after randomization, for repeat exercise testing and coronary angiogram. For patients in the medical arm, this exercise testing was performed while they continued their anti-anginal medications. In contrast, patients in the PTCA arm stopped their anti-anginal medications for at least 24 hours before the test.
Endpoints: The primary end points were changes in exercise tolerance, angina attacks and the use of nitroglycerin. Change in the degree of stenosis in the index lesion was measured as a secondary endpoint.
Analysis was performed based on the intention-to-treat principle. The sample size to achieve 95% power at an alpha level of 0.05 was 192. This was based on the assumption that PTCA would increase exercise duration by 1-minute compared to medical therapy. To account for potential loss to follow-up, the recruitment goal was set at 200 patients.
Results: Among the 105 patients assigned to PTCA, 95% underwent the procedure, and among them, the procedure was considered successful in 82%. Successful PTCA was defined >20% decrease in percent stenosis of all lesions in which dilation was attempted. Among the 107 patients assigned to medical therapy, 10% underwent PTCA.
The mean duration from randomization to follow-up exercise testing was approximately 7 months. PTCA led to greater increase in exercise time compared to medical therapy alone (2.1 minutes vs 0.5 minutes; p< 0.0001) as well as time to onset of angina (2.6 minutes vs 0.8 minutes; p <0.01). Patients in the PTCA arm had numerically greater reduction in angina episodes (-15/ month vs -7/ month; p= 0.06). Reduction in nitroglycerin use was not significantly different between both groups (-9/ month with PTCA vs -5/ month with medical therapy; p= 0.25).
There was no significant difference in myocardial infarction (4.8% with PTCA vs 2.8% with medical therapy; p= 0.50) or death (0.0% with PTCA vs 0.9% with medical therapy; p= 1.0). The one patient who died in the medical arm died as a result of a PTCA procedure.
The change in degree of stenosis was not significant in the medical arm (77% at baseline vs 75% at 6 months). In the PTCA arm, stenosis was reduced immediately after angioplasty (76% vs 36%) but then increased again at follow up to 54%.
Conclusion: In patients with single-vessel stable coronary artery disease, PTCA improved exercise duration and symptoms compared to medical therapy alone.
The study is limited by small sample size, but more importantly, it was highly selective, with only 2.2% of screened patients being enrolled. It is, however, valuable that the authors provided reasons for patients’ exclusions which helps physicians determine which of their patients would have qualified for the trial.
Another significant limitation is the lack of blinding, which could introduce bias in the assessment of symptoms and exercise capacity. Additionally, the results of PTCA were not durable, and lesions worsened during 6 months follow-up, compared to the initial results achieved.