Novel Approaches for Preventing or Limiting Events II - NAPLES II

Description:

The goal of the trial was to evaluate treatment with a loading dose of atorvastatin in statin-naïve patients undergoing elective percutaneous coronary intervention (PCI).

Hypothesis:

An 80 mg loading dose of atorvastatin administered within 24 hours prior to elective PCI would reduce the incidence of periprocedural myocardial infarction (MI), as measured by cardiac enzyme elevation.

Study Design

Study Design:

Patients Screened: 1,385
Patients Enrolled: 668
Mean Patient Age: 64.5 years
Female: 21%
Mean Ejection Fraction: 56%

Patient Populations:

  • Age ≥18 years
  • Patients with a de novo coronary artery stenosis
  • Patients undergoing elective PCI
  • Normal cardiac biomarkers
  • No current statin therapy

Exclusions:

  • Primary or rescue PCI
  • Acute coronary syndrome with elevated cardiac biomarkers
  • Pregnancy
  • Coronary artery restenosis
  • Treatment of a saphenous vein graft or left internal mammary artery graft
  • Active statin therapy

Primary Endpoints:

  • CK-MB elevation >3 times ULN at 6 and 12 hours after PCI, alone or associated with chest pain or ST-segment or T-wave abnormalities

Secondary Endpoints:

  • In-hospital death, MI, or repeat revascularization
  • Cardiac troponin I elevation >3 times ULN at 6 and 12 hours after PCI

Drug/Procedures Used:

Patients with coronary artery disease scheduled for elective PCI and not on statin therapy were randomized to an 80 mg loading dose of atorvastatin within 24 hours prior to PCI (n = 338), or no statin therapy (n = 330).

Concomitant Medications:

All patients received 100 mg of aspirin and 300 mg of clopidogrel on the day prior to the procedure. All patients received intravenous heparin during PCI to achieve an activated clotting time >250 seconds. Glycoprotein IIb/IIIa inhibitors were used in about 13% of the patients. On discharge, all patients were prescribed aspirin (325 mg/day), clopidogrel (75 mg/day, which was continued for 30 days after PCI with bare-metal stents, and for 6 months after drug-eluting stents), and atorvastatin (20 mg/day). Thirty-nine percent of patients in both groups received beta-blockers.

Principal Findings:

At presentation, 88% of patients were symptomatic, and 62% of patients had multivessel coronary disease. Baseline low-density lipoprotein cholesterol was about 128 mg/dl. Angiographic complications were low (5.6%).

The incidence of postprocedure myocardial infarction (MI) (creatine kinase-myocardial band [CK-MB] >3 times upper limit of normal [ULN]) was significantly lower in patients treated with atorvastatin (9.5% vs. 15.8%, 95% confidence interval [CI] 0.35-0.89, odds ratio [OR] 0.56, p = 0.01). The incidence of cardiac troponin I >3 times ULN was also significantly lower in patients treated with atorvastatin (26.6% vs. 39.1%, 95% CI 0.40-0.78, OR 0.56, p < 0.001).

Subgroup analysis suggested that the benefit of the atorvastatin load was most pronounced in patients with high C-reactive protein levels. The incidence of death, unplanned revascularization, and stent thrombosis was low, and not significantly different between groups, although the composite endpoint of death, MI, and revascularization was significantly lower in the atorvastatin arm (10% vs. 15.7%, p = 0.029).

Interpretation:

The ARMYDA trial demonstrated that atorvastatin administered 7 days prior to PCI is effective in reducing the incidence of postprocedure MI. The results from NAPLES II indicate that a single loading dose of atorvastatin given within 24 hours prior to PCI is also effective in reducing postprocedure MI. One limitation of this trial is that there was a higher incidence of angiographic complications in the control arm, including a 5-fold higher incidence of slow or no-reflow, compared with the statin arm, although this was not statistically significant. Whether this may have resulted in a higher rate of periprocedural MIs in the control arm is unknown.

It also remains unclear whether a single loading dose of atorvastatin is superior to 7 days of statin therapy prior to PCI; however, the results from NAPLES II suggest that a single loading dose of atorvastatin may be a reasonable treatment strategy for statin-naïve patients undergoing elective PCI.

References:

Briguori C, Visconti G, Focaccio A, et al. Novel approaches for preventing or limiting events (NAPLES) II trial: impact of a single high loading dose of atorvastatin on periprocedural myocardial infarction. J Am Coll Cardiol 2009;54:2157-2163.

Novel Approaches for Preventing or Limiting Events (NAPLES) II Trial: Impact of Loading Dose of Atorvastatin on Periprocedural Myocardial Infarction. Presented by Dr. Carlo Briguori at ACC.09/i2, Orlando, FL, March 2009.

Clinical Topics: Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and Coronary Artery Disease

Keywords: Odds Ratio, Coronary Artery Disease, Myocardial Infarction, Cholesterol, LDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Creatine Kinase, MB Form, Heptanoic Acids, Hypercholesterolemia, Stents, Percutaneous Coronary Intervention, Pyrroles, C-Reactive Protein, Biological Markers, Coronary Stenosis, Troponin I, Thrombosis, Confidence Intervals


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