麻豆传媒

BOSTON -- A PCSK9 inhibitor contributed extra LDL cholesterol lowering as an early add-on to standard high-intensity statins in the acute period of ST-segment elevation MI (STEMI), the small EPIC-STEMI trial found.

Between alirocumab (Praluent) and sham injections given right before percutaneous coronary intervention (PCI), and repeated at 2 and 4 weeks, patients had LDL cholesterol fall by 72.9% and 48.1%, respectively, for a between-group difference of -22.3% (P<0.001) at 6-week follow-up, according to Shamir Mehta, MD, MSc, of McMaster University and Hamilton Health Sciences, in Ontario, Canada.

The proportion of people meeting the LDL cholesterol target of 1.4 mmol/L (54 mg/dL) was 92.1% with alirocumab and 56.7% with sham (P<0.001). Additionally, approximately 89.5% of alirocumab recipients achieved at least a halving in LDL, compared with 60% of controls (P=0.007), he reported at the Transcatheter Cardiovascular Therapeutics (TCT) meeting hosted by the Cardiovascular Research Foundation. The findings were simultaneously published in .

Notably, participants did not have baseline LDL or statin use routinely assessed before being assigned to either treatment group. The early use of PCKS9 inhibition nevertheless "appeared feasible and safe" as a companion to standard statins at doses substantially higher than in previous PCSK9 inhibitor trials, Mehta stated.

He explained that the rationale for alirocumab in the acute STEMI setting is the inability for some people to reach optimal LDL levels even with "state of the art" statins that had entered routine use in the last decade.

"The point was to reach a broader population," he said at a TCT press conference. "We are missing high-risk patients by not treating them acutely."

Roxana Mehran, MD, of Mount Sinai School of Medicine in New York City, emphasized the "tremendous uptick" in ischemic events, including myocardial infarction (MI), in the first 30 days to 6 months post-STEMI.

Alirocumab's "fantastic reduction" in LDL cholesterol hopefully translates into reduced inflammation in these patients, akin to what has been observed in other populations, and better outcomes, she suggested at the press conference.

In 2015, the FDA made alirocumab the first approved PCSK9 inhibitor on the market for LDL lowering in some patients when used in conjunction with diet and maximally-tolerated statin therapy. The drug subsequently proved its clinical benefit in the ODYSSEY Outcomes trial, resulting in an for heart attack, stroke, and unstable angina reduction.

Regeneron and Sanofi have of alirocumab to encourage uptake, but Mehta acknowledged the difficulties with accessibility to this class of drugs that remain.

"Those are definitely issues but for us as physicians, we have to get the science right first, and if we do the trials and get the science right, practice will evolve," he said. "We're treading very carefully with PCSK9 inhibitors, inching forward across populations."

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

Investigators had 97 people randomized, though only 68 were included in the analysis due to clinic closures during the COVID-19 pandemic. This cohort averaged age 62, and there were some numeric differences between the alirocumab versus sham groups, such as fewer women (71% vs 93%) and more current smokers (42% vs 23%), respectively.

Exclusion criteria included pediatric patients, pregnant or breastfeeding women, current or planned treatment with PCSK9 inhibitors, allergy or contraindication to a PCSK9 inhibitor, and creatinine clearance <30 mL/min.

The alirocumab group received the PCKS9 inhibitor at a dose of 150 mg subcutaneously. Matching shams got an alirocumab pen lacking an internal needle so that injection could not be performed.

Mehta acknowledged that some sham patients could have been unblinded if they felt the lack of a needle in their assigned pen.

Study participants started the trial with LDL cholesterol at nearly 3 mmol/L at baseline. Following treatment, the alirocumab reached 0.72 mmol/L (27.8 mg/dL) LDL cholesterol and controls 1.29 mmol/L (49.9 mg/dL) LDL cholesterol.

LDL cholesterol crept back up over time after the last PCSK9 inhibitor injection.

Mehta noted that clinical events were low and not different between groups, though the study had not been powered for clinical outcomes. The ongoing randomized trial will study another PCSK9 inhibitor, evolocumab (Repatha), initiated in the setting of acute MI and its potential effects on long-term outcomes.

TCT press conference panelist, Eric Cohen, MD, of Sunnybrook Health Sciences Centre in Toronto, raised the question of whether PCSK9 inhibition might help or deter adherence to medical therapies among STEMI patients.

And imagine if secondary prevention looked like PCSK9 inhibitors just twice a year atop a polypill. "This is the future of prevention," Mehta said.

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

Comment