PCSK9 inhibitor bypassing aggregation to reduce LDL in acute coronary syndrome

Boston – A PCSK9 inhibitor contributed to an additional lowering of LDL cholesterol as an early addition to standard high-intensity statins in the acute period of ST-segment elevation MI (STEMI), EPIC-STEMI small trial finds.

Between leucomab (Praluent) and sham injections given immediately prior to PCI, and repeated at 2 and 4 weeks, LDL cholesterol decreased by 72.9% and 48.1%, respectively, with a difference between the two groups of -22.3% (s<0.001) at a 6-week follow-up, according to Shamir Mehta, MD, MSc, of McMaster University and Hamilton Health Sciences, in Ontario, Canada.

The proportion of subjects who met the LDL target of 1.4 mmol/L (54 mg/dL) was 92.1% with lerocumab and 56.7% with the sham images (s<0.001). In addition, approximately 89.5% of alirocumab recipients achieved at least halving their LDL, compared with 60% of the control group (s= 0.007), reported in Cardiovascular treatments via catheterization (TCT) meeting hosted by the Cardiovascular Research Foundation. The results were simultaneously published in EuroIntervention.

Notably, participants did not have LDL or baseline statin use routinely assessed prior to being assigned to any treatment group. Mehta stated that early use of PCKS9 inhibitor “appears feasible and safe” as an adjunct to standard statins at much higher doses than in previous PCSK9 inhibitor trials.

He explained that the rationale for iirocumab in acute ST-segment elevation myocardial infarction is the inability of some people to reach optimal LDL levels even with “modern” statins that have entered routine use in the past decade.

“The goal was to reach a larger population,” he told TCT’s press conference. “We are missing out on high-risk patients by not treating them acutely.”

Roxana Mahran, MD, a physician at Mount Sinai School of Medicine in New York City, emphasized a “massive rise” in ischemic events, including myocardial infarction (MI), in the first 30 days to 6 months after a hypertensive myocardial infarction.

At the press conference, she suggested that alirucumab’s “remarkable reduction” in LDL cholesterol translates to reduced inflammation in these patients, similar to what has been observed in other populations, and better outcomes.

In 2015, the US Food and Drug Administration made alirocumab First approved PCSK9 inhibitor On the market to lower LDL in some patients when used in combination with diet and maximally tolerated statin therapy. The drug later proved its clinical benefit in Trial Odyssey resultsResulting in FDA index expansion For the treatment of heart attacks, strokes and unstable angina pectoris.

Amgen has Lower the price of alirocumab to encourage absorption, but Mehta admitted to Difficulties in access For this class of the remaining drugs.

“These are certainly issues but for us as clinicians we have to get the right science first, and if we do experiments and get the right science, the practice will evolve,” he said. “We are proceeding very cautiously with PCSK9 inhibitors, and we are progressing slowly across populations.”

EPIC-STEMI was a blinded trial of myocardial infarction patients undergoing initial PCI who were randomly assigned to alirocumab or sham before primary PCI, a repeat intervention after 2 weeks and again after 4 weeks. Both study groups were given a high-dose statin (atorvastatin). [Lipitor] or rosuvastatin [Crestor] daily).

The investigators randomly assigned 97 people, although only 68 were included in the analysis due to clinic closures during the COVID-19 pandemic. This averaged age group was 62 years, and there were some numerical differences between the erucumab versus photo groups, such as fewer women (71% vs 93%) and current smokers (42% vs 23%), respectively.

Exclusion criteria included pediatric patients, pregnant or lactating women, current or planned treatment with PCSK9 inhibitors, allergies or contraindications to PCSK9 inhibitor use, and creatinine clearance <30 mL/min.

The lerucomab group received a PCKS9 inhibitor at a dose of 150 mg subcutaneously. The matching sun got an irocumab pen that lacked an internal needle so injections could not be done.

Mehta admitted that some sham patients would have been blind if they felt there was no needle in their pen.

Study participants started the trial with LDL cholesterol at approximately 3 mmol/L at baseline. After treatment, erucumab reached 0.72 mmol/L (27.8 mg/dL) LDL cholesterol and controlled 1.29 mmol/L (49.9 mg/dL) LDL cholesterol.

Low-density lipoprotein cholesterol rose again over time after the last injection of PCSK9 inhibitor.

Mehta noted that clinical events were low and did not differ between groups, although the study was not supported for clinical outcomes. Ongoing Evolve- MI The randomized trial will study another PCSK9 inhibitor, Evolocumab (Repatha), which has begun to identify acute MI and its potential effects on long-term outcomes.

TCT press conference committee member Eric Cohen, MD, Sunnybrook Health Sciences Center in Toronto, raised the question of whether inhibiting PCSK9 might help or prevent adherence to medical treatments among STEMI patients.

And imagine if secondary prevention was like PCSK9 inhibitors just twice a year over the multi-pill. “This is the future of prevention,” Mehta said.

  • Nicole Low She is a reporter at MedPage Today, where she covers cardiology news and other developments in medicine. Follow

Disclosures

EPIC-STEMI was funded by Sanofi and the Population Health Research Institute.

Mehta disclosed his relationships with and/or support from Sanofi/Hamilton Health Sciences, Amgen, Sanofi and Novartis. The co-authors disclosed relationships with, and/or support from, multiple entities.

Mahran revealed his service on the executive committee of Amgen’s EVOLVE-MI experiment.

Cohen has not disclosed any ties to the industry.