Alirocumab prior to PCI lowers LDL-C

Starting alirocumab early in the hospital prior to undergoing percutaneous coronary intervention (PCI) reduces LDL-cholesterol (LDL-C) in STEMI* patients already on high-statin therapy.

Compared with sham control, alirocumab reduced LDL-C by 22.3 percent in this randomized EPIC-STEMI** study.

The findings build the case for alirocumab, a PCSK9 inhibitor, even in patients not taking lipid-lowering therapies prior to myocardial infarction (MI) events, said lead investigator Dr Shamir Mehta from McMaster University/Population Health Research Institute in Hamilton, Canada, during his presentation at TCT 2022.

“Routine and early administration of a PCSK9 inhibitor have the potential to substantially reduce morbidity and mortality globally after high-risk acute coronary syndrome (ACS) by further reducing LDL-C beyond statins in a greater number of high-risk patients than is currently treated with these agents,” he added.

The use of high-intensity statin was 97 percent in the alirocumab group and 100 percent in the sham-control group. At a median of 45 days, LDL-C level decreased by 72.9  with alirocumab vs 48.1 percent with the sham control (p<0.001). [EuroIntervention 2022;doi:10.4244/EIJ-D-22-00735]

Additionally, more patients in the alirocumab group achieved the European Society of Cardiology/European Atherosclerosis Society dyslipidaemia guideline target of LDL-C ≤1.4 mmol/L vs 56.7 percent in the sham control arm (p<0.001)

More evidence for early PCSK9 inhibition

Similar reductions in LDL-C were seen in other recent trials of early PCSK9 inhibition in patients with ACS. [J Am Coll Cardiol 2019;74:2452-2462; Circulation 2020;28;142:419-421]

“EPIC-STEMI adds to the results of these trials as it evaluates initiation of a PCSK9 inhibitor routinely to patients with STEMI before primary PCI, irrespective of baseline LDL-C or prior statin use,” Mehta said.

Early initiation of high-intensity statin, regardless of LDL-C levels, is the standard practice in patients with STEMI. Researchers sought to determine if initiating a PCSK9 inhibitor early, on top of high-intensity statin, would have added benefits in STEMI.

Sixty-eight STEMI patients were randomly assigned to alirocumab 150 mg given subcutaneously or a sham injection before PCI regardless of baseline LDL-C levels or prior statin use. Subsequent injections were given at 2 and 4 weeks.

Within the first 24 hours after PCI, LDL-C dropped slightly more rapidly with alirocumab than with the sham control (p=0.03), but the difference was not significant until about 2 weeks, said Mehta. “We know that early high-intensity statin therapy is effective in this setting, [but] adding a PCSK9 inhibitor takes this concept to a different level.”

As for the NT-proBNP or C-reactive protein levels, there were no differences between the groups.

In a press conference prior to his presentation, Mehta said the point of conducting the trial was to reach a broader population of ACS patients who were not taking a PCSK9 inhibitor.

“We are missing these high-risk patients because we are not treating them acutely,” he said. “We wanted to give them the best drugs available when they are coming in with a major life-threatening event.”

In the same press conference, Dr Roxana Mehran from the Icahn School of Medicine at Mount Sinai, New York, New York, US said the first 30 days to 6 months after PCI are critical for STEMI patients as they face an increased risk of recurrent MI. The potential for a PCSK9 inhibitor to help with plaque stabilization or inflammation reduction during this crucial period is a strategy that “absolutely warrants” investigation.

Dr Eric Cohen from Sunnybrook Health Sciences Centre, Toronto, Canada couldn’t agree more. “STEMI patients typically come to the hospital on zero medications and leave two days later on five medications,” he said. “Having a PCSK9 inhibitor injection every 2 weeks could have an impact on pill burden or patient adherence to therapy.”