Add PCSK9 inhibitors to statins in primary PCI: EPIC-STEMI

It is preferable for patients to have strong lipid-lowering therapy before hospital discharge after acute ST segment elevation myocardial infarction (STEMI), so why not immediately start – even in a catheter lab – using some of the most powerful
Available LDL-lowering agents?

This was a key idea behind the fake-controlled randomness EPIC-STEMI The trial, in which patients with ST-segment elevation myocardial infarction started with a PCSK9 inhibitor immediately prior to direct therapy Percutaneous coronary artery intervention using percutaneous coronary catheters (PCI) and above
High intensity statins.

Participants in the trial who received the active agent showed a 22% reduction in LDL cholesterol levels in 6 weeks compared to the control group given a dummy injection along with HDLs. They were also more likely to meet LDL Targets set in some guidelines, including a reduction of at least 50%. These results were achieved regardless of baseline LDL levels or previous statin use.

Adopting an early and robust LDL-lowering strategy in practice “has the potential to significantly reduce morbidity and mortality” in such cases “by further reducing LDL beyond statins in a much larger number of Patients at high risk from what is currently being treated. These clients,” lead researcher Shamir R Mehta, MD, MSc, suggested when presenting the results Sept. 19 in Transcatheter Cardiovascular Therapies (TCT) 2022 in Boston, Massachusetts.

Adherence to secondary prevention measures in patients with Acute coronary syndromes Mehta, chief scientist at the Population Health Research Institute and professor of medicine at McMaster University, Hamilton, Canada, explained that ACS is much better if started before discharge from hospital. But “once a patient leaves the hospital, it becomes more difficult to get these treatments on board.”

Routine adoption of such in-hospital lipid-lowering therapy for a large population with ACS would likely mean significantly fewer deaths and cardiovascular events ‘across a wide range of patients’.

EPIC-STEMI is among the first studies to explore strategy. “I think that’s the point of the experiment we wanted to do, which is that we don’t have data on this yet. We’re very cautious with PCSK9 inhibitors, and they’re slowly progressing in the population. And I think we need a bold experiment to see if that’s going to change things.” or not “.

PCSK9 inhibitor erucomab (Praluent) was used in EPIC-STEMI, which posted in EuroIntervention, with Mehta as lead author, on the same day as his presentation at TCT. The drug was given and dummy injected over either of them atorvastatin 40-80 mg or rosuvastatin 40 mg.

Early initiation of statins in patients with acute ST-segment elevation myocardial infarction is now standard, but there is good evidence from intracoronary imaging studies to suggest that addition of PCSK9 inhibitors may enhance the stability of plaques that may cause recurrent ischemic events. .

Treatment with parenteral drugs in addition to statins significantly reduced coronary lesion in Glagov Experience of stable coronary patients. Initiation of PCSK9 inhibitors with high-intensity statins soon after PCI for ACS also improved the reduction of atherosclerosis in non-infarction-associated arteries over the course of 1 year last controlled with placebo. Bachman Amy Experience.

Mehta noted that the reductions of LDL upon PCSK9 inhibition, compared to a placebo control, were not necessarily as impressive as would be expected from major trials of long-term treatment with the drugs.

“You need longer [therapy] In order to see a difference in LDL levels when a PCSK9 inhibitor was used acutely. This is also shown in infarct volume scales. There was no difference between treatment groups in infarct size as measured by MB fraction levels creatine Kinase, reported.

“What this tells us is that acute use of the PCSK9 inhibitor did not change the magnitude or severity of the underlying STEMI event.”

EPIC-STEMI was too small and was never intended to evaluate clinical outcomes; It was more about feasibility and what degree of LDL reduction to expect.

Mehta said the trial is necessary because PCSK9 inhibitors have not been widely adopted in clinical practice and are not reaching patients who could benefit most. One of the reasons for this is quite obvious to him. “We are missing high-risk patients because we are not treating them acutely,” Mehta said. theheart.org | Medscape Heart.

He noted that the strategy “has not yet been evaluated, and there were obstacles.” “Cost was a barrier. Getting the drug was a barrier. But in terms of the science, in terms of reducing cardiovascular events, this is a strategy that needs to be tested.”

An aggressive early LDL-lowering strategy should be evaluated in terms of its effect on long-term outcomes, “particularly given that in the first 30 days to 6 months after hypertensive myocardial infarction there is a dramatic rise in ischemic events , including recurrent myocardial infarction,” Roxana Mahran, MD, at an EPIC-STEMI media conference held prior to the official presentation of Mehta.

The “remarkable, acute reduction” with a PCSK9 inhibitor over statins, said Mahran, of the Icahn School of Medicine at Mount Sinai, “we hope to reduce inflammation” similar to what has been observed in previous trials, “completely warrants” the trial of clinical outcomes for STEMI, New York City, Who is not connected to EPIC-STEMI.

If better adherence to medication after hospital discharge is one of the goals of the acute strategy, it will be important to consider the potential impact of prescribing a medication that is injected periodically, as suggested by Eric A. Cohen, MD, Sunnybrook Health Sciences Center, Toronto, Canada, at a news conference.

“Keep in mind that patients with ST-segment elevation myocardial infarction usually come to the hospital without any medications and leave after two days on five medications,” Cohen noted. “I’m curious if having one of these injections as a sub-injection every two weeks, and reducing the burden of birth control pills, would help or deter adherence to treatment. I think it’s worth studying.”

The trial originally included 97 patients undergoing PCI for STEMI who were randomly assigned to receive a PCSK9 inhibitor or placebo over high-intensity statins, without regard to LDL levels. Randomization occurred after diagnostic angiography but before percutaneous coronary intervention.

However, the analysis later excluded 29 patients who were unable to follow up on the study, “mainly due to the closure of a hospital research clinic due to the COVID-19 pandemic,” the published report states.

That left 68 patients who received at least one dose of the PCSK9 inhibitor, alirocumab 150 mg subcutaneously, or a placebo, and had at least one blood draw for an LDL response which, Mehta said, still leaves sufficient statistical power for protein-based LDL. . primary end point.

By 6 weeks, LDL cholesterol levels were reduced by 72.9% in the active treatment group and by 48.1% in the control group (s <.001). Also, 92.1% and 56.7% of patients, respectively (s = .002), achieved levels below the 1.4 mmol/L (54 mg/dL) target in European guidelines, Mehta reported.

Levels decreased by more than 50% compared to baseline in 89.5% of erucumab patients and 60% (s = .007) of the controls, respectively.

There was no significant difference in rates of LDL levels below the 70 mg/dL (1.8 mmol/L) threshold set by the US guidelines for very high-risk patients: 94.7% of aliurocumab patients and 83.4% of the control group (s = .26).

The groups also did not differ significantly in natriuretic peptide levels, which reflect ventricular remodeling. or in a 6-week change in highly sensitive C-reactive protein to an inflammatory biomarker.

An open-label randomized trial, due to launch within weeks, will explore similarly early initiation of a PCSK9 inhibitor compared to standard Fat management In an estimated 4,000 hospitalized patients with or without myocardial infarction.

The evolve MI The trial is looking at a monoclonal antibody evolocumab (Repatha) for its effect on the primary end point of myocardial infarction, ischemic strokeor arterial revascularization or death from any cause within an expected 3 to 4 year period.

EPIC-STEMI is supported in part by Sanofi. Mehta reported an unrestricted grant from Sanofi to Hamilton Health Sciences for tuition and current counseling fees from Amgen, Sanofi, and Novartis. Disclosures to other authors in the report.

Cohen reveals that he received grant support from Abbott Vascular and held research contracts with it; and receive a consulting fee, fee, or service at the speaker desk for Abbott Vascular, Medtronic, and Baylis.

Mahran reveals receiving grants or research support from Abbott Vascular, AstraZeneca, Bayer, Bristol-Myers Squibb, CSL Bering, Daichi Sankyo/Eli Lilly, Medtronic, Orbus Niche, Abiomed, Boston Scientific, Allephant, Amgen, AM-Pharma Applied Therapeutics, Arena, BAIM, Biosensors, Biotronik, CardiaWave, CellAegis, Concept Medical, CeloNova, CERC, Chiesi, Cytosorbents, Duke University, Element Science, Faraday, Humacyte, Idorsia, Insel Gruppe, Philips, RenalPro, Vivasure, Zoll; Receiving consultant fees, fees, or service in the speaker office for Novartis, Abbott Vascular, Janssen, Medtronic, Medscape/WebMD, and Cine-Med Research; and holding stock, stock or stock options with Control Rad, Applied Therapeutics and Elixir Medical.

Transcatheter Cardiovascular Therapies 2022. Advanced clinical science in coronary artery disease: Sixth session, in cooperation with the secondment. It was introduced on September 19, 2022.

EuroIntervention. Posted online September 19, 2022. Summary

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