PCSK9 inhibition before PCI for STEMI further reduces LDL on top of statin therapy
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BOSTON — PCSK9 inhibition before primary PCI for STEMI, on top of standard statin therapy, significantly lowered LDL at 6 weeks compared with sham control, according to the results of the EPIC-STEMI trial presented at TCT 2022.
The findings were simultaneously published in EuroIntervention.
“In patients with STEMI, early initiation of high-intensity statin therapy, regardless of baseline LDL, is standard practice worldwide. It didn’t start that way,” Shamir R. Mehta, MD, MSc, FRCPC, FACC, FESC, director of interventional cardiology at Hamilton Health Services and professor in the division of cardiology at McMaster University in Hamilton, Ontario, Canada, said during a press conference. “It started with treating only high-risk patients after a delay and only if their LDL was elevated. That progressed over the last decade and a half to routine treatment with statins, regardless of LDL levels. The greater the reduction in LDL with statins, the lower the risk, and there is no apparent lower limit on which a benefit is not observed.
“A significant proportion of patients with STEMI never achieve optimal LDL levels with statins. PCSK9 inhibitors further reduce LDL and events, but they have not been studied when given acutely nor as routine treatment, similar to the way we administer statins,” Mehta said. “Whether a simplified regimen of initiating PCSK9 inhibitor routinely in the acute setting of STEMI on top of high-intensity statins would add additional benefit by further reducing LDL cholesterol in a much wider population of patients is not known on a population level.”
Mehta and colleagues designed the randomized EPIC-STEMI trial to test routine administration of early PCSK9 inhibition, regardless of baseline LDL, prior to PCI for STEMI. Thirty-eight patients (mean age, 61 years; 71% men) were assigned to high-dose alirocumab (Praluent, Sanofi/Regeneron) before primary PCI and 30 more were assigned to sham control (mean age, 64 years; 93% men).
The primary outcome was percent change in LDL from baseline at 6 weeks.
All patients received a daily high-dose statin (atorvastatin 40 mg or 80 mg or rosuvastatin 40 mg daily).
At 6 weeks, LDL levels fell 72.9% in the PCKS9 inhibitor group and 48.1% in the sham control group (mean between-group difference, –22.3%; 95% CI, –31.1 to –13.5; P < .001), according to the researchers.
After PCSK9 withdrawal at 6 weeks, the difference in LDL was no longer significant compared with sham (P = 1).
Mehta and colleagues reported that 89.5% of patients assigned to early PCSK9 inhibition achieved a more than 50% LDL reduction compared with 60% of the sham group (OR = 5.67; 95% CI, 1.59-20.13; P = .007).
More patients in the PCSK9 inhibitor group achieved a LDL of 1.4 mmol/L or less compared with sham (92.1% vs. 56.7%; OR = 8.62; 95% CI, 2.01-53.42; P = .002).
“The big unknown is whether or not achieving this level of LDL reduction will translate to reduction in clinical events,” Mehta said during the press conference. “This implies that a randomized trial is needed in order to assess this strategy in a much larger patient population compared with usual care.”
Reference:
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Mehta SR, et al. Late-Breaking Clinical Science in Coronary Artery Disease: Session VI, in Collaboration With Circulation. Presented at: TCT Scientific Symposium; Sept. 16-19, 2022; Boston (hybrid meeting).
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