SECURE-PCI: 'Statin Loading' in ACS Doesn't Cut 30-Day Event Risk

March 12, 2018

ORLANDO — The risk for clinical events at 30 days in a trial that enrolled a broad population with acute coronary syndrome (ACS) was not affected by administration of two 80-mg loading doses of atorvastatin, one given before and the other after planned invasive management.

That primary finding does not support the early statin-loading strategy broadly in ACS, say investigators. But in a prespecified subgroup analysis, it led to a significant 28% drop in risk for events when invasive management included percutaneous coronary intervention (PCI).

The more than 4000 patients in the study, called Statins Evaluation in Coronary Procedures and Revascularization (SECURE-PCI), had unstable angina or acute myocardial infarction (MI) with or without ST-segment elevation (STEMI and NSTEMI, respectively).

They had been randomly assigned to receive high-dose statin or placebo right before and 24 hours after coronary angiography with discretionary revascularization. All patients then received atorvastatin at 40 mg/d for a month.

The lack of effect on major adverse cardiac events (MACE) overall, paired with the significant benefit in the PCI subgroup, which appeared to be driven by fewer MIs, drew varying reactions after the trial's presentation here at the American College of Cardiology (ACC) 2018 Annual Scientific Session.

Some observers said it has a message for practice that's actionable now, while others were enthused at the finding in PCI recipients but said it would need a randomized trial to back it up before it could be recommended.

Because early loading of atorvastatin was essentially safe and pointed to a benefit in PCI recipients, the strategy is reasonable to consider in patients with ACS who proceed to coronary revascularization, Otavio Berwanger, MD, PhD, from the Research Institute–Heart Hospital, São Paulo, Brazil, said when presenting the study here.

It could be made part of the standard emergency department (ED) experience for some patients with ACS, Berwanger observed for theheart.org | Medscape Cardiology.

"I think for patients for whom there's a very high likelihood of undergoing PCI, at centers that do a lot of PCI in STEMI patients, it would make a lot of sense." That is based, he said, not only on SECURE-PCI but also on prior small observational studies and meta-analyses.

Berwanger is also lead author on the trial's publication in JAMA, which appeared online about the same time as his live presentation at the sessions.

"They're Low Risk, So Why Not?"

Speaking at a press conference on SECURE-PCI, Craig Beavers, PharmD, University of Kentucky College of Pharmacy, Lexington, largely agreed with Berwanger. "There appears to be no harm doing that strategy," he said, referring to high-intensity statin loading, initiated in the ED, in patients with ACS likely to get PCI.

"It may ensure that people don't miss these drugs upon arrival, to start them up front. They're low risk, so why not?"

Indeed, it now seems appropriate that a decision whether to do statin loading in that setting can be up to the provider on a case by case basis, observed Erin A Bohula, MD, DPhil, Brigham and Women's Hospital, Boston, Massachusetts, in an interview.

She said many clinicians would take the view of "We know the benefit's there in ACS, and we don't think there's any risk per se, so why not do it up front?" It's well established that statin therapy improves clinical outcomes in patients who have had an ACS event.

"Clinical intuition and all the data suggests that it's a good thing to treat patients early on in ACS, but I can't definitively say it should be done right before PCI," said Bohula, who is not associated with SECURE-PCI.

"I think the only situation where I could imagine as a clinician that I might pause is: Am I going to hold up that STEMI patient from getting their PCI by trying to get them on a statin prior to PCI? I would probably push to do the PCI, as opposed to prioritize the statin," she said.

"Otherwise, if you've got someone who comes in with an NSTEMI, they will be going to cath in 48 hours. So you may as well give them the statin up front. There's no downside to that."

Other Takes: More Research Indicated

SECURE-PCI "answered a very important question," said Neil J Stone, MD, Northwestern Feinberg School of Medicine, Chicago, Illinois, as a panelist after Berwanger's formal presentation of the trial: that is, the primary result does not support that everyone presenting with ACS be loaded right away with a high-intensity statin.

"The first question I think about when I practice — because I don't like to guess when I can know — I start with randomized controlled trials, because then I'm no longer guessing," he said. The secondary results of SECURE-PCI suggesting that statin loading reduces the risk for MACE, according to Stone, means a new trial addressing that issue specifically is needed.

The trial's finding in PCI recipients should not be applied in practice, at least not yet, agreed Robert O Bonow, MD, also from Northwestern Feinberg School of Medicine, who isn't connected to SECURE-PCI.

"We need to digest this a little more, but it could be that in the future, someone coming in with presumed or established ACS, who's going to the cath lab, maybe you would load them in the ED with high-intensity statins. This could evolve in that direction," Bonow told theheart.org | Medscape Cardiology.

"But that was not the take-home message of the intention-to-treat analysis, because there was no effect," he said. Still, he added, "you can't ignore the PCI data, they're actually quite impressive."

An editorial accompanying the trial's publication takes a similar tack. "The take-home message of the SECURE-PCI study is that the routine use of loading doses of atorvastatin among ACS patients with intended invasive management cannot be supported," write Stephen J Nicholls, MBBS, PhD, and Peter J Psaltis, MBBS, PhD, both from the University of Adelaide, Australia.

Although the positive result in PCI recipients "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."

"Whether such therapy should be administered as soon as possible in the ACS hospitalization remains to be fully elucidated," they write. "SECURE-PCI certainly provides reassurance that such early administration is not associated with harm."

Loading-Dose Strategy

The trial, conducted at 53 centers in Brazil, randomly assigned 4191 patients with STEMI, NSTEMI, or unstable angina that was to be invasively managed, about 70% of whom had been receiving long-term statin therapy within the prior 6 months, to the loading-dose strategy with atorvastatin or placebo.

The two 80-mg atorvastatin doses were given to 2087 patients right before catheterization and 24 hours later, and 2104 patients received corresponding placebos.

Ultimately, 64.7% of the total cohort underwent PCI, 8% received bypass graft surgery, and 27.3% were medically managed without revascularization.

The two groups showed similar 30-day rates of MACE, defined as a composite of death from any cause, acute MI, stroke, or unplanned coronary revascularization. The rates were 6.2% for those getting atorvastatin loading and 7.1% for controls. There are also no significant differences overall for the individual MACE components.

The significant effect of atorvastatin loading seen in the PCI group appeared to be driven by a reduction in new MIs; none of the other MACE components showed an interaction with PCI status.

Table. Hazard Ratio (HR) for Outcomes, Loading-Dose Atorvastatin vs Placebo, Overall and by Subgroups

Endpoints Hazard Ratio (95% CI) P Value
MACEa at 30 d (primary outcome), overall 0.88 (0.69 - 1.11) .27
With PCI: MACE at 30 d after invasive management 0.72 (0.54 - 0.96) .02
With PCI: New MI at 30 d after invasive management 0.68 (0.47 - 0.99) .04
No PCI: MACE at 30 d after invasive management 1.59 (0.63 - 4.06) .54
aMACE refers to death from any cause, acute MI, stroke, and unplanned coronary revascularization.

 

There were no reported cases of rhabdomyolysis or hepatic failure, noteworthy potential adverse effects of statin therapy, in the atorvastatin-loading group. Three cases of rhabdomyolysis were reported among controls, according to the published report.

Berwanger reports receiving grants and/or fees from Astra Zeneca, Amgen, Bayer, Novo Nordisk, Boehringer Ingelheim, Roche Diagnostics, and Sanofi. Beavers had no disclosures. Bohula discloses receiving consulting fees or honoraria from Daiichi Sankyo, Merck, and Servier and research grants from Eisai. Stone had no disclosures. Bonow disclosed an unspecified relationship with Gilead. Nicholls reports receiving research support from AstraZeneca, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, the Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and Liposcience; and consultant fees from AstraZeneca, Amgen, Eli Lilly, Anthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, Kowa, CSL Behring, Esperion, and Boehringer Ingelheim. Psaltis reports receiving research support from Abbott Vascular and honoraria from AstraZeneca, Merck, Pfizer, Esperion, and Bayer.

American College of Cardiology (ACC) 2018 Annual Scientific Session. Presentation 404-16. Presented March 11, 2018.

JAMA. Published online March 11, 2018. Abstract, Editorial

Follow Steve Stiles on Twitter: @SteveStiles2. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....