Atorvastatin Reload Prior to PCI for Patients on Chronic Statin Therapy
Abstract & Commentary
By Andrew J. Boyle, MD, Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco. Dr. Boyle reports no financial relationships relevant to this field of study.
Source: Di Sciasio G, et al. Efficacy of Atorvastatin Reload in Patients on Chronic Statin Therapy Undergoing Percutaneous Coronary Intervention. Results of the ARMYDA-RECAPTURE (Atorvastatin for Reduction of Myocardial Damage During Angioplasty) Randomized Trial. J Am Coll Cardiol. 2009;54:558-565.
The ARMYDA (Atorvastatin for Reduction of Myocardial Damage During Angioplasty) series of randomized, controlled trials has assessed the role of atorvastatin loading prior to percutaneous coronary intervention (PCI) in both stable and unstable coronary syndromes. In patients who are naïve of statin therapy, a loading dose of atorvastatin prior to PCI reduces the incidence of peri-procedural myocardial infarction (MI). However, many patients referred for PCI already are receiving statin therapy. Whether a repeat loading dose of atorvastatin in patients who are on chronic statin therapy also reduces periprocedural events was not known. In the latest of the series, the ARMYDA-RECAPTURE study, the authors addressed this issue, performing a multi-center, randomized, controlled trial of atorvastatin reload versus placebo prior to PCI in patients on chronic statin therapy.
Patients who were taking any type of statin therapy at any dose for at least 30 days, and who were referred for PCI for either stable angina or ischemia or non-ST elevation acute coronary syndromes (ACS), were screened. Exclusion criteria included ST elevation, ACS with high-risk features, requiring emergency coronary angiography, abnormal liver function tests, left ventricular ejection fraction < 30%, renal failure with serum creatinine > 3mg/dL, or a history of muscle or liver disease. Patients were randomized to either atorvastatin (80 mg loading given 12 hours before coronary angiography, with a further 40 mg dose approximately two hours before the procedure, n = 192) or placebo at the same times (n = 191). All patients received aspirin 100 mg/day and clopidogrel 600 mg before the procedure, and continued aspirin indefinitely and clopidogrel 75 mg daily for at least one month, but for 12 months for those receiving a drug-eluting stent or presenting with ACS. All patients received atorvastatin 40 mg/day regardless of treatment assignment or prior statin therapy. The primary endpoint was 30-day incidence of MACE (major adverse cardiac events), defined as cardiac death, MI, or target vessel revascularization. Secondary endpoints were MI, serum C-reactive protein (CRP) levels, and MACE in prespecified subgroups.
The baseline characteristics were well matched between cohorts and were typical of coronary intervention trials, being predominantly male, mean age 66 years, and a 36% diabetes prevalence. Nearly half the patients (46%) presented with ACS. The mean duration of statin therapy prior to the procedure was nine months in both groups. The primary endpoint of 30-day MACE occurred in 3.7% in the atorvastatin group and 9.4% of the placebo group (p = 0.037). This was primarily driven by higher rates of periprocedural MI (3.7% vs. 8.9% respectively). Patients with ACS had lower MACE rates with atorvastatin reload (3.3% vs. 14.8%; p = 0.015), but patients with stable angina did not (4.0% vs. 4.9%; p = 0.98). CRP levels did not differ between groups before or after PCI. The authors performed multivariable analysis to identify predictors of risk of 30-day MACE. Atorvastatin reload was associated with a 50% reduction in relative risk of MACE (p = 0.039), and there was no difference in the benefit found when adjusting for the type of stent or antithrombin used during the index procedure. Logistic regression revealed an 82% relative risk reduction in MACE with atorvastatin reload in patients presenting with ACS (OR 0.18, 95% CI 0.10 to 0.83; p = 0.027) but no reduction in patients with stable angina (OR 0.74, 95% CI 0.20 to 2.9; p = 0.70). DiSciasio et al conclude that reloading with high-dose atorvastatin improves the clinical outcome of patients on chronic statin therapy undergoing PCI.
Commentary
Patients on chronic statin therapy presenting with ACS had reduced incidence of periprocedural MI with atorvastatin reloading. This finding is in keeping with the results of previous ARMYDA studies, and has direct clinical relevance. While the exact mechanism by which atorvastatin reduces periprocedural myocardial necrosis remains unknown, DiSciasio et al postulate several possible mechanisms. These include a reduction in inflammatory cytokine release, possible antiplatelet effects of atorvastatin, and recruitment of endothelial progenitor cells to the site of injury to stimulate the healing response. Whatever the mechanism, the results of the present study are consistent with prior studies in statin-naïve patients with ACS who also derive benefit from atorvastatin loading before PCI. Importantly, the authors noted no benefit from atorvastatin reload in patients on chronic statin therapy who presented with stable angina or ischemia.
Notably, the use of glycoprotein IIb/IIIa inhibitors was low in this study (12%), despite the fact that half the patients presented with acute coronary syndromes. It is not known if these results would hold true if more patients received IIb/IIIa inhibitors. Thus, the results may not be directly applicable in the United States, where IIb/IIIa inhibitor use is much more common.
The ARMYDA (Atorvastatin for Reduction of Myocardial Damage During Angioplasty) series of randomized, controlled trials has assessed the role of atorvastatin loading prior to percutaneous coronary intervention (PCI) in both stable and unstable coronary syndromes.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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