Atorvastatin loading before percutaneous coronary intervention improves outcomes in patients with acute coronary syndrome

1. In this prespecified secondary analysis of a randomized controlled trial, patients with acute coronary syndrome (ACS) who received a loading dose of atorvastatin prior to percutaneous coronary intervention (PCI) and again 24 hours post-PCI had lower rates of major adverse cardiovascular events at 30 days compared with patients who received placebo.

2. These results were driven largely by patients presenting with ST-elevation myocardial infarction (STEMI).

Evidence Rating Level: 2 (Good)

Study Rundown: Statin therapy after PCI for acute coronary syndrome (ACS) is considered evidence based standard of care, as patients with ACS are at high risk for early recurrent coronary events. Regarding statins prior to PCI, several meta-analyses over the last 8 years have supported the hypothesis that high dose statin therapy prior to PCI improves outcomes. However, the optimal timing of statin administration is not clear. In the Statin Evaluation in Coronary Procedures and Revascularization (SECURE-PCI) trial, loading dose of atorvastatin did not show any benefit in the overall population of patients presenting with ACS. However, this prespecified secondary analysis evaluated only patients who went on to receive PCI. Compared with patients receiving placebo, patients who received 80 mg atorvastatin within 24 hours pre-PCI and again 24 hours post-PCI had reduction in MACE and MI at 30 days. The effect was seen whether or not patients were previously on statin therapy. The reduction in MACE and MI was driven largely by patients presenting with ST-elevation myocardial infarction.

While the strong study design and follow-up rates support these findings, it is noteworthy that the majority of patients were male, and the study excluded patients with fibrate intake 24 hours prior to the study loading dose. In addition, this was a subgroup analysis of the original study, which reduces the validity of the results. Overall, this study provides additional evidence that there is benefit of high dose statin therapy anytime in the 24 hours prior to PCI.

Click to read the study in JAMA Cardiology

Relevant Reading: Evidence of pre-procedural statin therapy a meta-analysis of randomized trials

In-Depth [subgroup analysis of randomized controlled trial]: The Statins Evaluation in Coronary Procedures and Revascularization (SECURE-PCI) trial was a randomized, double-blind, pragmatic, multicenter trial conducted in Brazil. 4191 patients were recruited from 53 sites between April 18, 2012 and October 6, 2017 and were randomized to receive either 80 mg of atorvastatin or placebo prior to planned invasive management of acute coronary syndrome and again 24 hours post-invasive management. Planned invasive management was described as coronary angiography +/- PCI within 7 days. Of the 4191 patients, 2710 (64.7%) underwent PCI and were part of a prespecified subgroup analysis. This study was based on the subgroup that underwent PCI for management of ACS. The primary outcome was MACE (composite of all-cause mortality, acute MI, stroke, and unplanned coronary revascularization) at 30 days. The secondary outcomes included each component of MACE as well as cardiovascular death, stent thrombosis, and target vessel revascularization. Patients were excluded if they were pregnant or breastfeeding, women under 45 not on contraception, history of drug hypersensitivity, or advanced liver disease, concurrent enrollment in another trial using hypolipemiant agents, maximum dose statin therapy or any fibrate intake in the last 24 hours, or age older then 18 years of age.

At 30 days, 6.0% of patients in the atorvastatin group had MACE, compared with 8.2% of patients in the placebo group (HR 0.72, 95% CI 0.54-0.97 p=0.03). This represented an overall reduction of 28% in rates of MACE. There was also lower rates of myocardial infarction at 30 days in the atorvastatin group (HR 0.68, 95% CI 0.47-0.99, p=0.04). The treatment effect was largely seen in patients presenting with STEMI (HR 0.59, 95% CI 0.38-0.92, p=0.02) rather than with NSTE-ACS (HR 0.85, 95% CI 0.58-1.27, p=0.43). The treatment effect was not statistically significant depending on time of administration (within 2 hours of PCI, 2-4 hours prior to PCI, 4-12 hours prior to PCI, or 12-24 hours prior to PCI). The treatment effect was consistent regardless of prior statin use. There was no benefit in the atorvastatin group for patients who underwent CABG or medical management in place of PCI. There were no cases of rhabdomyolysis or hepatic failure in the atorvastatin group, and levels of creatine phosphokinase and aminotransferases were not significantly different at 30 days.

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