PCSK9 inhibitor tested for lowering LDL in acute coronary syndrome

Boston – PCSK9 inhibitor as early addition to standard high-intensity statin in acute phase of ST-segment elevation MI (STEMI) to help additionally lower LDL cholesterol, small EPIC- STEMI trial findings.

Between alirocumab (Praluent) and sham injections given before percutaneous coronary intervention (PCI) and repeat injections at 2 and 4 weeks, patients’ LDL cholesterol decreased by 72.9 % and according to Shamir Mehta, MD, at 6-week follow-up, the between-group difference was 48.1% (P

The proportion of people who achieved an LDL cholesterol target of 1.4 mmol/L (54 mg/dL) was 92.1% alirocumab and 56.7% sham (PP=0.007) (TCT) conference hosted by the Cardiovascular Research Foundation. The findings were also published in EuroIntervention .

Of note, participants were not routinely assessed for baseline LDL or statin use prior to being assigned to either treatment group. Despite the early use of PCKS9 inhibitors as companions to standard statins, it “appears to be feasible and safe,” Mehta said, at doses much higher than previous PCSK9 inhibitor trials.

He explained that alirocumab in the acute STEMI setting is the “state of the art” statin that some people fail to achieve optimal LDL levels, even though it has entered routine use over the past decade.

“The point is to reach a wider population,” he said in a TCT news release. “We don’t treat high-risk patients in a timely manner.”

Roxana Mehran, MD, of Mount Sinai School of Medicine in New York City, highlights a “substantial increase” in ischemic stroke in the first 30 days after STEMI Events including myocardial infarction (MI) occurred within 6 months. She presented the results observed in other populations and better results in a news conference.

In 2015, the FDA made alirocumab the first PCSK9 inhibitor approved on the market for lowering LDL when used in combination with diet and a maximally tolerated statin in some patients. The drug subsequently demonstrated clinical benefit in the ODYSSEY Outcomes trial, expanding the FDA’s indication for reducing heart attack, stroke and unstable angina.

Regeneron and Sanofi have slashed the price of alirocumab to encourage uptake, but Mehta admits that difficulty accessing the drug remains.

“These are definitely questions, but for us as physicians we have to get the science right first, and if we experiment and get the science right, the practice will evolve,” he said . “We are using PCSK9 inhibitors very cautiously, progressively advancing in the population.”

EPIC-STEMI was a blinded trial of STEMI patients undergoing primary PCI who were They were randomized to alirocumab or sham PCI before initial treatment, repeated 2 weeks later, and again after 4 weeks. Both study groups also received high-dose statins (atorvastatin [Lipitor] or rosuvastatin [Crestor] daily).

Researchers randomly assigned 97 people, but because only 68 people were included in the analysis, clinics were closed during the COVID-19 pandemic. The mean age of the cohort was 62 years, and there were some numerical differences between the alirocumab and sham groups, such as fewer women (71% vs 93%) and more current smokers (42% vs 23%).

Exclusion criteria included pediatric patients, pregnant or breastfeeding women, current or planned treatment with PCSK9 inhibitors, allergy or contraindications to PCSK9 inhibitors, and creatinine clearance

The alirocumab group received a PCKS9 inhibitor at a dose of 150 mg subcutaneously. The matching sham was given an alirocumab pen without an internal needle, so the injection could not be performed.

Mehta acknowledges that some sham patients may be unblinded if they feel the assigned needle is missing.

Study participants at baseline LDL cholesterol levels are close to 3 mmol/L. After treatment, alirocumab achieved 0.72 mmol/L (27.8 mg/dL) LDL cholesterol and controlled 1.29 mmol/L (49.9 mg/dL) LDL cholesterol.

Time to gradual recovery of LDL cholesterol after last injection of PCSK9 inhibitor.

Mehta noted that clinical events were low and there were no differences between the groups, although the study did not power the clinical outcomes. The ongoing EVOLVE-MI randomized trial will investigate another PCSK9 inhibitor, evolocumab (Repatha), initiated in the context of acute MI and its potential impact on long-term outcomes.

TCT press conference panelist Eric Cohen, MD, of the Sunnybrook Health Sciences Centre in Toronto, raised the question of whether PCSK9 inhibition might help or prevent STEMI patients from adhering to their medication.

Imagine if secondary prevention looked like biannual PCSK9 inhibitors. “This is the future of prevention,” Mehta said.

Correction: This story has been updated to reflect that Regeneron and Sanofi have lowered the price of alirocumab.

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  Nicole Lou is a reporter for MedPage Today covering cardiology news and other medical developments. follow