Atorvastatin for Reduction of Myocardial Damage During Angioplasty-Acute Coronary Syndromes - ARMYDA-ACS – Presented at ACC 2007

Description:

The goal of the trial was to evaluate the effect of atorvastatin compared with placebo among patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI).

Study Design

Study Design:

Patients Screened: 771
Patients Enrolled: 171
Mean Follow Up: 30 days
Mean Patient Age: Mean age, 66 years
Female: 21

Patient Populations:

Non–ST-segment elevation ACS (unstable angina or non–ST-segment elevation acute MI) sent to early coronary angiography within 48 hours

Exclusions:

ST-segment elevation acute MI; non–ST-segment elevation ACS with high-risk features warranting emergency coronary angiography; any increase in liver enzymes; left ventricular ejection fraction <30%; renal failure with creatinine >3 mg/dl; history of liver or muscle disease; or previous or current treatment with statins

Primary Endpoints:

30-day MACE defined as death, MI, or unplanned revascularization

Secondary Endpoints:

Postprocedural increase of markers of myocardial injury above the upper limit of normal (CK-MB, troponin-I, myoglobin); postprocedural variations from baseline CRP levels

Drug/Procedures Used:

Patients were randomized in a double-blind manner to pretreatment with atorvastatin (80 mg 12 hours prior to PCI and 40 mg immediately pre-PCI; n = 86) or matching placebo (n = 85). After the procedure, all patients were treated with atorvastatin 40 mg indefinitely. Blood samples for biomarker evaluation were drawn immediately pre-PCI and at 8 and 24 hours post-PCI.

Concomitant Medications:

Clopidogrel 600 mg loading dose at least 3 hours pre-PCI and 75 mg/day post-PCI for at least 6 months; aspirin 100 mg/day indefinitely

Principal Findings:

Patients who were randomized but did not undergo PCI were excluded from the study (n = 10 in each arm). Of these 20 patients, 8 were treated medically and 12 underwent bypass surgery.

The index event was unstable angina in 64% of patients and non-ST elevation myocardial infarction (MI) in 36%. Multivessel disease was present in 40% of patients, and multivessel intervention was performed in 25% of cases. Glycoprotein IIb/IIIa inhibitors were used in 24% of patients. The vessel treated was the left anterior descending in half of the cases. Mean time to angiography was approximately 23 hours.

The primary endpoint of death, MI, or unplanned revascularization was lower in the atorvastatin group compared with the placebo group (5% vs. 17%, p = 0.01), driven by a reduction in periprocedural MI (5% vs. 15%, p = 0.04). Post-PCI creatine kinase-myocardial band (CK-MB) elevations occurred in fewer patients in the atorvastatin group than the placebo group (7% vs. 27%, p = 0.001), as did troponin-I elevations (41% vs. 58%, p = 0.039). The percent increase in C-reactive protein (CRP) from pre- to post-PCI was lower in the atorvastatin group (63% vs. 147%, p = 0.01). There were no deaths by 30 days in either group, and one unplanned revascularization in the placebo group.

Interpretation:

Among patients with ACS undergoing PCI, pretreatment with atorvastatin 80 mg was associated with a reduction in major adverse cardiac events (MACE) at 30 days compared with placebo, driven exclusively by a reduction in periprocedural MI.

Results of the present study are similar to the original ARMYDA study, which also showed a reduction in periprocedural MI with atorvastatin pretreatment but in a low-risk, stable angina, elective PCI population. When feasible, treatment with a loading dose of atorvastatin pre-PCI appears promising. However, the optimal timing of the pretreatment load is unknown, as is the impact of delaying PCI to pretreat with atorvastatin in an ACS population. Pretreatment in the present study was for 12 hours and mean time to PCI was 23 hours, but in an unstable population, time to revascularization is often shorter.

While the mechanism of action for the reduction of myocardial injury in the atorvastatin arm is not clear, the authors suggest the anti-inflammatory effect of statins may contribute to the reduction. The relative lower increase in CRP post-PCI in the atorvastatin arm supports this potential mechanism of action.

References:

Patti G, Pasceri V, Colonna G, et al. Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial. J Am Coll Cardiol 2007;49:1272-8.

Presented by Dr. Germano Di Sciascio at the American College of Cardiology Annual Scientific Session, New Orleans, LA, March 2007.

Clinical Topics: Acute Coronary Syndromes, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Stable Ischemic Heart Disease, ACS and Cardiac Biomarkers, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and ACS, Interventions and Imaging, Angiography, Nuclear Imaging, Chronic Angina

Keywords: Acute Coronary Syndrome, Myocardial Infarction, Angina, Stable, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Creatine Kinase, MB Form, Coronary Disease, Heptanoic Acids, Percutaneous Coronary Intervention, Pyrroles, C-Reactive Protein, Coronary Angiography, Troponin I


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