PCSK9 inhibitors before PCI rapidly lower LDL-C in ACS patients: EPIC-STEMI

Starting erucomab in the hospital dropped lipids to levels not seen in placebo-treated patients, paving the way for larger trials.

Boston, MA – Early initiation of a PCSK9 inhibitor in ST-segment elevation myocardial infarction patients prior to initial PCI procedures causes rapid decreases in LDL cholesterol levels, even against a background of high-intensity statins, results of the small, randomized EPIC-STEMI study show.

With only 68 patients, the trial did not provide any insights into the clinical effect of severe reduction, however, starting alirocumab (Praluent; Sanofi/Regeneron) had no effect on STEMI infarct size.

However, the authors say, the findings identify a role for the PCSK9 inhibitor, even in patients who were not already on lipid-lowering therapies prior to their MIs.

“Early routine administration of a PCSK9 inhibitor has the potential to significantly reduce global morbidity and mortality after high-risk ACS by reducing LDL beyond statins in a much larger number of high-risk patients than is currently treated with these agents,” Shamir R Mehta. MD (McMaster University/Population Health Research Institute, Hamilton, Canada), who presented the results of EPIC-STEMI earlier this week during a recent clinical scientific session at TCT 2022.

The results were simultaneously published in EuroIntervention.

In historical trials, PCSK9 inhibitors, given as injections twice monthly, were usually started months to years after the original ACS event, and only in patients already being treated with high doses of statins. Other recent experiences, including Evopax And the faxtested early onset of PCSK9 inhibitors and showed a similarly rapid drop in LDL cholesterol, while Bachman Amy showed that erucumab started early after ACS resulted in greater regression and stabilization of coronary plaques compared to placebo.

“EPIC-STEMI adds to the results of these trials because it evaluates initiation of a PCSK9 inhibitor routinely for patients with STEMI prior to primary PCI regardless of LDL cholesterol levels or previous statin use,” write Mehta et al.

Sham-controlled design

EPIC-STEMI randomized 68 STEMI patients to subcutaneous 150 mg or a dummy injection (using the active alirocumab pen but no internal needle) upon arrival at the catheter lab, regardless of baseline LDL cholesterol levels, with follow-up doses at 2 and 4 weeks. High-intensity statin use was also initiated in both groups; Only 16 patients were taking statins before the ACS event.

At a median of 45 days, LDL cholesterol levels were reduced by 72.9% in the erucumab group compared to 48.1% in the sham-treated patients (s <0.001). More than 92% of patients in the active treatment arm met or exceeded the European Society of Cardiology/European Society of Atherosclerosis guideline target - 1.4 mmol/L LDL-cholesterol (<55 mg/L) - compared to 56.7% in the Active Therapy arm. Sham (s <0.001).

We wanted to give patients the best medicine we have available when they come across a major life-threatening event. Shamir R Mehta

The intended benefit of rapid initiation of alirocumab was a reduction in infarct size, as measured by the CKMB area under the curve, but no differences were shown between groups,” suggesting that very early initiation of alirocumab may not alter volume or severity of an event, the investigators say. STEMI indicator.

For TCTMD, Mehta speculated that it would likely take some time after PCSK9 inhibited the LDL receptor for it to be upregulated enough to lower circulating LDL levels. “While we experienced a slightly faster decrease in LDL within the first 24 hours with alirocumab, the difference wasn’t significant until about two weeks ago. “We know that early, high-intensity treatment with statins is effective in this setting, [but] Adding a PCSK9 inhibitor takes this concept to a different level.”

There were no differences in the levels of NT-proBNP or C-reactive protein between the groups.

Where do I go from here

While discussing the trial with the press before his late presentation, Mehta stressed that the goal of the trial was to try to reach a larger group of patients for PCSK9 inhibition, noting that only 1% of patients who had previously had ACS are currently taking these drugs.

“There are a variety of [reasons] For that, but one reason is that we miss out on high-risk patients because we don’t treat them acutely. “So in this particular case, we wanted to give patients the best medicine we have available when they come in for a major life-threatening event.”

He continued, “If you look at history, that’s how statins were initially given. They were introduced very selectively – initially only lipids gave statins – and then migrated into the heart disease population. And then they were only given to a select number of Patients with acute coronary syndrome, until we get to the point where patients are. [them] Within hours of having STEMI.”

He noted that routine administration of statins at the time of hospital admission for ACS, regardless of LDL cholesterol levels, has become standard practice worldwide. “We think the same may be true with PCSK9 inhibitors, which have not yet been evaluated.”

In the case of these particular injectable drugs, there have been significant barriers to their absorption, most notably cost, but also issues with access and ease of use. “But in terms of the science and in terms of reducing cardiovascular events, this is a strategy that needs to be tested.”

Commenting on the study for the press, Roxana Mahran, MD (Icahn School of Medicine at Mount Sinai, NY, NY) noted that the first 30 days to 6 months are particularly critical for hypertensive myocardial infarction patients who are at risk High for myocardial infarction frequency. during this weak phase. The possibility that a PCSK9 inhibitor could help stabilize plaque or reduce inflammation during this period is a strategy that “absolutely warrants” evaluation.

one study experience, Evolve- MIAlready underway, she indicated.

Eric Cohen, MD (Health Sciences Center in Sunnybrook, Toronto, Canada) also commented at the press conference, noting the fact that ACS is usually a tipping point for many patients. “Keep in mind that patients with ST-segment elevation myocardial infarction usually come to the hospital without medication and leave after two days on five medications,” he said. This raises the possibility that subcutaneous injections of a PCSK9 inhibitor every two weeks may have an effect on pill burden or adherence to treatment, he said. “I think it’s worth studying.”