PCSK9 inhibitors before PCI rapidly reduce LDL-C in patients with ACS : EPIC-STEMI
Starting alirocumab in the hospital caused lipids to drop to levels never before seen in sham-treated patients, paving the way for larger trials.
BOSTON, MA – Early initiation of a PCSK9 inhibitor in STEMI patients before their primary PCI procedures leads to rapid declines in LDL cholesterol levels, even against high-intensity statin therapy, according to results from the small randomized study EPIC-STEMI .
With only 68 patients, the trial offers no insight into the clinical impact of aggressive reduction, and initiation of alirocumab (Praluent; Sanofi/Regeneron) had no impact on height STEMI infarction.
Still, say the authors, the findings reserve a role for a PCSK9 inhibitor, even in patients who were not yet taking lipid-lowering therapies prior to their myocardial infarction.
“Early and routine administration of a PCSK9 inhibitor has the potential to significantly reduce worldwide morbidity and mortality after high-risk ACS by further reducing LDL beyond statins in a much larger number of high-risk patients than what is currently being treated with these agents,” said Shamir R. Mehta, MD (McMaster University/Population Health Research Institute, Hamilton, Canada), who presented the EPIC-STEMI results earlier. this week during a last-minute clinical science session at TCT 2022.
The results were published simultaneously in EuroIntervention.
In landmark trials, PCSK9 inhibitors, given as twice-monthly injections, were typically started months to years after the initial ACS event, and only in patients previously treated with high-dose statins. Other recent trials, including EVOPACS and EVACS, tested earlier onset of PCSK9 inhibitors and showed similar and rapid reductions in LDL cholesterol, while PACMAN-AMI demonstrated that alirocumab started soon after ACS resulted in greater regression and stabilization of coronary plaque versus placebo.
“EPIC-STEMI adds to the results of these trials as it systematically assesses PCSK9 inhibitor initiation in patients with STEMI prior to primary PCI, regardless of baseline LDL cholesterol levels or prior use. of statins,” write Mehta et al.
Dummy control design
The EPIC-STEMI study randomized 68 patients with STEMI to receive 150 mg alirocumab subcutaneously or as a sham injection (using an active alirocumab pen but without an internal needle) at their arrival at the catheterization laboratory, regardless of the initial LDL cholesterol level, with follow-up doses at 2 and 4 weeks. High-intensity statins were also initiated in both groups; only 16 patients were taking a statin before their ACS event.
After a median of 45 days, LDL cholesterol levels were reduced by 72.9% in the alirocumab group compared to 48.1% in the sham-treated patients (P P
We wanted to give patients the best medicine we have when they arrive with a major life-threatening event. Shamir R. Mehta
A hoped-for benefit of rapid initiation of alirocumab was a reduction in infarct size, as measured by CKMB area under the curve, but no difference was observed between groups, “suggesting that very early initiation of alirocumab may not alter the size or severity of the STEMI index event,” the investigators state.
For TCTMD, Mehta hypothesized that it likely takes some time after PCSK9 inhibition for LDL receptors to be up-regulated enough to drive down circulating LDL levels. “Although we saw a slightly faster drop in LDL in the first 24 hours with alirocumab, the difference was not significant until about 2 weeks,” he said. “We know that in this setting, early high-intensity statin therapy is effective, [but] adding a PCSK9 inhibitor takes this concept to a different level.
There was no difference in NT-proBNP or C-reactive protein levels between the groups.
Where to go from here
Discussing the trial with the press ahead of his last-minute presentation, Mehta emphasized that the purpose of the trial was to try to reach a wider population of patients for PCSK9 inhibition, noting that only 1% of patients who have had ACS in the past are currently taking these drugs.
“There are a variety of [reasons] for that, but one of the reasons is that we miss high-risk patients because we don’t treat them acutely,” he said. “So in this particular case, we wanted to give patients the best medicine we have when they come in with a major life-threatening event.”
Notably, he continued, “if you look at history, that’s how statins were initially introduced. They were introduced very selectively – initially only lipidologists were giving statins – then they migrated to the cardiology population. And then they were only given to a select number of patients who had had acute coronary syndrome, until we got to the point where patients [them] within hours of a STEMI. »
Routine administration of statins at the time of hospital admission for ACS, regardless of LDL cholesterol level, has become standard practice worldwide, he noted. “We think the same may be true with PCSK9 inhibitors, it just hasn’t been evaluated yet.”
In the case of these particular injectable drugs, there have been major barriers to adoption, including cost, but also issues related to access and ease of use. “But in scientific terms and in terms of reducing cardiovascular events, it’s a strategy that needs to be tested.”
Commenting on the study to the press, Roxana Mehran, MD (Icahn School of Medicine at Mount Sinai, New York, NY), noted that the first 30 days to 6 months are especially critical for STEMI patients who face risk high recurrent MI during this vulnerable phase. The potential for a PCSK9 inhibitor to help stabilize plaque or reduce inflammation during this time is a strategy that “absolutely warrants” evaluation.
A study trial, EVOLVE-MI, is already underway, she noted.
Also commenting at the press conference, Eric A. Cohen, MD (Sunnybrook Health Sciences Centre, Toronto, Canada), highlighted the fact that an ACS is usually a turning point for many patients. “Keep in mind that STEMI patients typically arrive at the hospital with zero medication and leave 2 days later with five medications,” he said. This raises the possibility, he said, that a subcutaneous injection of a PCSK9 inhibitor every 2 weeks could have an impact on pill burden or treatment adherence. “I think it’s worth studying.”