Acolysis During Treatment of Lesions Affecting Saphenous Vein Bypass Grafts - ATLAS - SVG

Description:

The goal of the Acolysis During Treatment of Lesions Affecting Saphenous Vein Bypass Grafts (ATLAS) trial was to compare the effect of acolysis (therapeutic ultrasound) versus abciximab in patients with saphenous vein grafts (SVGs) undergoing vein graft intervention.

Hypothesis:

Among patients undergoing a vein graft intervention, pretreatment with acolysis followed by balloon angioplasty or stenting would be associated with an equivalent, if not superior, outcome to administration of abciximab during balloon angioplasty or stenting.

Study Design

Study Design:

Patients Enrolled: 181
Mean Follow Up: One year
Mean Patient Age: 69 years
Female: 14%

Patient Populations:

1) Unstable angina, ischemic ST changes on resting electrocardiography, recent MI within 24 hours before intended treatment, or a positive stress test; 2) an SVG with one or two lesions requiring treatment that had not been treated in the prior 30 days and in which no other intervention was planned in the next 30 days; 3) left ventricular ejection fraction 25% or more; 4) creatine kinase (CK) and CK-MB levels within normal range at the time of the procedure; 5) angiographic evidence of thrombus, or, in cases of an occluded graft, clinical symptoms within the past 30 days suggestive of recent clot in the target vessel; and 6) 60% or more stenosis in a graft 2.0 mm or larger in diameter

Exclusions:

1) Thrombolysis within the prior seven days; 2) hypersensitivity to aspirin, heparin, or abciximab; 3) a major gastrointestinal bleed within six months, major operation within six weeks, or stroke within the prior two years; 4) severe uncontrolled hypertension; 5) planned treatment at more than two sites in one graft or planned treatment in more than one target vessel; and 6) inability to cross a total occlusion with a guidewire

Primary Endpoints:

Frequency of successful procedures, defined as a final diameter stenosis of ≤30%, achievement of Thrombolysis in Myocardial Infarction (TIMI) 3 flow, and freedom from MACE (cardiac death, Q wave and non–Q wave MI, emergency bypass, repeat target lesion revascularization, and disabling stroke) within 30 days of treatment

Drug/Procedures Used:

Patients were randomized either to acolysis (n=92) followed by percutaneous transluminal coronary angioplasty (PTCA) or stent implantation, or to abciximab (n=89) followed by balloon dilation and stent implantation.

The acolysis probe delivers a therapeutic level of ultrasound at the treatment site, pulling the thrombus toward the catheter tip, where it is lysed or liquefied to subcapillary size. The trial was designed as an equivalency study and planned to enroll 540 patients.

Concomitant Medications:

At least one aspirin (325 mg) per day before the procedure and ticlopidine. Weight-adjusted heparin was given to maintain activated clotting time >300 seconds in the acolysis arm, and 200-300 seconds in the abciximab arm.

Principal Findings:

The trial was discontinued early, due to a Data Safety and Monitoring Board (DSMB) recommendation after a significantly higher incidence of adverse clinical outcomes occurred in the acolysis arm. Angiographic procedural success occurred less frequently in the acolysis arm (62.5%) versus the abciximab arm (82.1; p=0.008).

Device failure or malfunction occurred in 14 patients in the acolysis arm. Major adverse cardiac events (MACE) by 30 days were more frequent in the acolysis arm (25%) versus the abciximab arm (12.4%; p=0.036), due mainly to a higher rate of non-Q wave myocardial infarction (MI) with acolysis (19.6% vs. 7.9%, p=0.03). Most of the MACE events occurred during the first postprocedural day: 23% in the acolysis arm and 9% in the abciximab arm. Angiographically evident distal embolization did not differ between the two arms (7.6% in the acolysis arm vs. 11.2% in the abciximab arm, p=0.45).

The primary endpoint of procedural success and freedom from MACE at 30 days occurred in 53.8% of acolysis patients and 73.1% of abciximab patients (p=0.014). MACE remained higher at one-year follow-up (39.1% in the acolysis arm vs. 22.5% in the abciximab arm, p=0.017), as did the frequency of non-Q wave MI (23.9% vs. 10.1%, p=0.017).

Interpretation:

Among patients undergoing a vein graft intervention, pretreatment with acolysis followed by balloon angioplasty or stenting was associated with a lower rate of successful procedure and freedom from MACE compared to administration of abciximab during balloon angioplasty or stenting. Due to the higher event rates in the acolysis arm, the trial was discontinued early at the suggestion of the DSMB.

The authors suggest that the higher rate of MI in the acolysis arm may be due to fragmenting the thrombus by the ultrasound into smaller particles, resulting in occlusion of the microvasculature and distal embolization. The majority of the 30-day MACE events were non-Q wave MIs and occurred early post-procedure, which would also support the hypothesis of embolization and microvascular occlusion due to the procedure.

Limited therapies exist that have been shown to successfully improve outcomes in patients with occluded vein grafts undergoing intervention. The PercuSurge GuardWire distal embolic protection device, which was studied in the SAFER trial, was associated with lower rates of MACE at 30 days.

References:

Singh M, Rosenschein U, Ho KK, Berger PB, Kuntz R, Holmes DR Jr. Treatment of saphenous vein bypass grafts with ultrasound thrombolysis: a randomized study (ATLAS). Circulation. 2003;107:2331-6.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention

Keywords: Myocardial Infarction, Follow-Up Studies, Creatine Kinase, Platelet Aggregation Inhibitors, Reference Values, Microvessels, Immunoglobulin Fab Fragments, Constriction, Pathologic, Electrocardiography, Angioplasty, Balloon, Coronary, Stents, Equipment Failure, Embolic Protection Devices, Thrombosis, Saphenous Vein, Stroke Volume, Exercise Test


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