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Study Summary

Prior studies have suggested loading acute coronary syndromes (ACS) patients with high-dose statins may attenuate the ischemic cascade and reduce periprocedural acute myocardial infarctions (MIs). In this double-blinded, multicenter trial, 4191 adult ACS patients were randomized to receive atorvastatin 80 mg or placebo 2-12 hours before coronary angiography and a second dose 24 hours after the planned intervention. All patients then received atorvastatin 40 mg for 1 month. At 30 days, the primary end point — all-cause mortality, acute MI, stroke, or unplanned revascularization — did not differ between the statin and placebo arms (6.2% vs 7.1%, HR 0.88, 95% CI 0.69-1.11, p = 0.27). However, among those who had a percutaneous coronary intervention (64.7%), major adverse cardiovascular events had occurred in 6.0% of the atorvastatin group vs. 8.2% in the control group (p = 0.02), driven by the MI rate (3.6% vs 5.2%, p = 0.04) (see accompanying Hurst’s Central Illustration). There were no reports of liver failure and only 3 cases of rhabdomyolysis (0.3%) in the placebo arm, confirming the safety of statins.

Effect of Atorvastatin Loading Dose Prior to PCI


Study Strengths: The trial was well designed with an intention to treat analysis and with a large sample size. The ACS patients included around 25% with ST-Elevation Myocardial Infarction (STEMI); 60%, Non ST-Elevation Myocardial Infarction (NSTEMI); and 14.5%, unstable angina. Both arms received comparable, guideline-directed medical therapy for ACS. Though the trial did not show significant differences in the primary outcome, importantly the PCI subgroup analysis did show reduction in MACE with no reports of liver failure or rhabdomyolysis.

Study Limitations: The study group was heterogeneous. Interestingly, around 27% of the patients presenting with ACS did not undergo coronary revascularization (PCI or CABG) and 3% did not have a confirmed ACS diagnosis which may have contributed to a lack of overall benefit. Importantly, because the investigators could not ethically withhold stain therapy, the treatment group only differed from the placebo arm in the two loading doses of atorvastatin 80 mg but both continued with atorvastatin 40 mg daily for 30 days. Interestingly, LDL levels at 30 days were 79.6 mg/dl in the treatment group vs. 75.8 mg/dl in the placebo arm! Thus, the stain effect may have benefited both groups and mitigated the impact of the 2 loading doses given to the treatment arm.

Next Steps/Clinical Perspective: It may be worthwhile to consider studying the impact of statin treatment targeting a very low dose LDL (goal of < 50 mg/dL) to a non-targeted treatment group in patients undergoing ACS and routine PCI. This trial reinforces routine clinical practice to treat ACS patients with high-intensity statin therapy and possibly lends support to the practice of loading with 2 doses of atorvastatin 80 mg 2-12 hours prior to angiography and then 24 hours later.

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