Atorvastatin Versus Revascularization Treatments - AVERT

Description:

Aggressive lipid-lowering therapy for ischemic events in 1- or 2- vessel CAD.

Hypothesis:

To assess the effect of aggressive lipid-lowering therapy on ischemic events in low-risk patients with single- or double- vessel CAD.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 341
Mean Follow Up: 18 months
Mean Patient Age: 58
Female: 16
Mean Ejection Fraction: 61%

Patient Populations:

Documented single- or double-vessel CAD
≥50% stenosis in target lesion
High LDL (≥115 mg/dL or ≥3.0 mmol/L)
LVEF ≥40%
Able to exercise ≥4 minutes on a Bruce protocol or bicycle exercise protocol without developing ischemia

Primary Endpoints:

Occurrence of ischemic events (death, nonfatal MI, cerebral vascular accident, CABG, angioplasty, hospitalization due to worsening angina).

Secondary Endpoints:

Time to first ischemic event.

Drug/Procedures Used:

Aggressive lipid lowering (atorvastatin 80 mg/day) plus usual medical therapy vs. angioplasty plus usual care, including standard lipid lowering.

Principal Findings:

The AVERT trial randomized patients to either high-dose atorvastatin and usual medical therapy (n=164) or angioplasty plus usual care, including standard lipid lowering (n=177).

In the angioplasty/usual care group, there was an 18% reduction in LDL from a baseline of 145 mg/dl to 119 mg/dl. In the atorvastatin group, there was a 46% reduction in LDL from 143 mg/dl to 77 mg/dl.

There was a small but statistically significant benefit favoring angioplasty with respect to angina class. In the atorvastatin group, 67 patients (41%) improved, 78 patients (47.5%) had no change, and 19 patients (11.5%) deteriorated. For the angioplasty group, 95 patients (54%) improved, 70 patients (39%) had no change, and 12 patients (7%) deteriorated.

For the primary endpoint of total ischemic events, 22 atorvastatin patients (13%) had events compared to 37 patients (21%) in the angioplasty group. This 36% relative reduction corresponded to a p-value of 0.048, which was not statistically significant after adjustment for the two interim data reviews. The incidence of death (0.6% vs 0.6%) and infarction (2.4% vs 2.8%) was not different between the atorvastatin and the angioplasty groups, respectively. There were 9 CABG procedures and 21 subsequent percutaneous interventions in the angioplasty group, compared to 2 CABG procedures and 18 percutaneous interventions in the atorvastatin group. There were 11 admissions for angina in the atorvastatin group compared to 25 admissions for the PTCA group. For the secondary endpoint of time to first ischemic event, there was a 36% risk reduction (95% CI 5% to 67%, p=0.027) at 18 months. Forty nine percent of all ischemic events occurred within the first six months of follow-up.

For the first 6 months, event curves for time to first ischemic event were similar for both groups; however, at 6 months the lines began to diverge and were continuing to diverge at the end of the study, with the atorvastatin group showing a significant time delay to first ischemic event compared to the angioplasty group (p=0.027).

There were no significant differences in AST or ALT levels, or incidence of new malignancies.

Interpretation:

The patients enrolled in AVERT were extremely low-risk, with stable CAD, 1 or 2 vessel CAD, and normal ventricular function. The primary endpoint, although clinically interesting, was not statistically significant after alpha adjustment for interim analyses. The low-risk patient population randomized to angioplasty in this study may not reflect the population of patients that receive percutaneous interventions in clinical practice. The AVERT trial provides supportive evidence that aggressive lipid-lowering therapy may provide clinical benefit in patients with stable angina. It appears that the beneficial effect of atorvastatin on ischemic events does not appear until six months from the onset of therapy, probably due to plaque stabilization and a reduction in new lesion development.

References:

1. Presented at 71st Scientific Sessions, American Heart Association, Dallas TX, 1998.

Clinical Topics: Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: Pyrroles, Myocardial Infarction, Follow-Up Studies, Risk Reduction Behavior, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Ventricular Function, Constriction, Pathologic, Heptanoic Acids, Angioplasty


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