Statin preloading falls short in ACS
High-dose statin preloading does not cut the 30-day event risk in patients with acute coronary syndrome (ACS) in the SECURE-PCI* study. But in patients with ST-segment elevation MI (STEMI) undergoing percutaneous coronary intervention (PCI), preloading with high-dose atorvastatin reduced the risk of major adverse cardiac events (MACE).
Administration of two 80-mg loading doses of atorvastatin, one given before and the other after a planned PCI, did not reduce the primary outcome of MACE or the composite of all-cause mortality, myocardial infarction (MI), stroke, and unplanned coronary revascularization. At 30 days, there was only a trend toward a reduction in MACE in the atorvastatin preloading arm vs placebo (hazard ratio [HR] 0.88, 95 percent CI, 0.69-1.11; p=0.27).
However, in the prespecified subgroup analysis of 2,710 patients who underwent PCI, atorvastatin preloading led to a significant 28-percent reduction in the risk for MACE vs placebo (p= 0.02). There was also 32 percent reduction in the risk of MI (p= 0.04), including a 58 percent reduction in the risk of non-PCI-related MI (p= 0.04). The benefit appeared to be driven by fewer MIs unrelated to PCI. [ACC.18, abstract 18-LB-17893]
The study included 4,191 patients (mean age 61.8 years, 1,085 were women) from 53 sites in Brazil with ACS, randomized to loading doses of atorvastatin or a matching placebo before and 24 hours after a planned PCI. All patients received atorvastatin 40 mg for 30 days 24 hours after the second dose of study medication. Of the total number, 64.7 percent underwent PCI, 8 percent underwent coronary artery bypass graft (CABG) surgery, and 27.3 percent were managed medically. [JAMA 2018;doi:10.1001/jama.2018.2444]
Negative trial with positive subgroup
“The trial must be interpreted as a negative trial with a positive subgroup,” said lead investigator Dr Otavio Berwanger from the Research Institute-Heart Hospital in São Paulo, Brazil, who presented the results at ACC.18. “It should be considered hypothesis-generating. And for patients whom PCI is very likely, such as those with STEMI, statin preloading is reasonable to consider.”
The lack of effect on MACE overall, coupled with the significant benefit in the PCI subgroup, drew mixed reactions from experts. In a panel discussion after the presentation, Dr Neil Stone from the Northwestern University Feinberg School of Medicine, Chicago, Illinois, US, said the overall study result does not support high-intensity statin dosing in every patient presenting with ACS. “I don’t like to guess when I can know and I start with randomized controlled trials,” he said. “The trial answered a very important question: if we take all-comers, should we load them with high-dose atorvastatin?” The answer is “no,” but it does not mean physicians should not give high-dose statins to ACS patients, Stone added.
No safety concerns
Dr Erin Bohula from the Brigham and Women’s Hospital in Boston, Massachusetts, US, who is unaffiliated with the study, said while the overall result of SECURE-PCI was negative, there were no safety concerns raised with statin preloading. “We know that aggressive lipid-lowering is good in the setting of ACS and PCI, and while we don’t have proof yet that very early dosing is useful, I also don’t think it’s harmful. So, I walk away saying: ‘Sure, if I can, I’ll give it [to my patients] as early as possible.’”
In an accompanying editorial, Drs Stephen Nicholls and Peter Psaltis from the University of Adelaide in Australia said the take-home message is that the routine use of loading doses of atorvastatin among ACS patients with intended invasive management cannot be supported. To what degree this reflects sample size, based on an ambitious assumed event rate reduction, remains uncertain. “Although findings in patients who underwent PCI can be viewed only as hypothesis generating, it provides some ongoing enthusiasm that very early use of high-intensity statin therapy may be of benefit in the right patients,” they said. [JAMA 2018;doi:10.1001/jama.2018.2426]
Current guidelines already recommend the use of high-dose statins for ACS. “SECURE-PCI certainly provides reassurance that such early administration is not associated with harm,” Nicholls and Psaltis added.
To add to that, Berwanger said the results may help guide clinicians on how to start statins in the early phase of ACS, particularly in STEMI patients undergoing PCI. He said further study is warranted to identify the mechanisms behind the benefit observed in patients who underwent PCI.