Key Points:
- Early high-intensity statin therapy is standard of practice in acute STEMI patients, but this is often insufficient to achieve LDL targets. PCSK-9 therapy has never been tested as routine therapy in STEMI.
- In the EPIC STEMI trial, routine PCSK-9 initiation in addition to high-intensity statin prior to primary PCI resulted in a 22% LDL reduction at 6 weeks relative to sham, with a higher proportion of patients achieving therapeutic LDL targets.
Early high-intensity statin initiation is standard of practice after STEMI regardless of starting LDL; however, even despite this therapy, many patients never achieve optimal LDL levels. PCSK-9 inhibitors are known to further reduce LDL level when other lipid-lowering therapy is insufficient, but they have been studied either as an acute post-STEMI treatment or as an empiric, routine therapy. In a breaking presentation at the 2022 TCT Conference today, Dr. Shamir Mehta (McMaster University, Canada) and his team presented their study: “Effects of Routine Early Treatment with PCSK-9 Inhibitor in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction,” or the EPIC STEMI trial.
The EPIC STEMI study (NCT03718286) was a randomized, double-blind, single center placebo controlled parallel group clinical trial conducted in Hamilton, Ontario which evaluated the effects of acute treatment with alirocumab (a PCSK-9 inhibitor) compared with placebo on LDL levels in patients presenting with STEMI undergoing PCI. The inclusion criteria comprised adults with STEMI referred for primary PCI, randomized within 12 hours of symptom onset and prior to coronary angiography; relevant exclusions included current or prior PCSK-9 treatment or contraindication, Killip class ≥2, or creatinine clearance <30mL/min. 68 patients were randomized (prior to primary PCI) to either 150mg alirocumab or sham control; both treatments were administered again at 2 and 4 weeks post PCI. All patients additionally received high intensity station therapy. The mean age was 62, and 81% of patients were male. 37% had pre-existing dyslipidemia, and 8.8% had diabetes.
The primary outcome was percent reduction in direct LDL-cholesterol at 6 weeks. Patients receiving alirocumab experienced a 22.3% LDL reduction (95% CI -31.1, -13.5; p <0.001); additionally, LDL was significantly reduced in the alirocumab group at 2 and 4 weeks, but the difference ceased to be significant at 12 weeks post alirocumab withdrawal. The alirocumab group were also significantly more likely to achieve the target of >50% LDL reduction at 6 weeks (OR 5.67, 95% CI 1.59-20.13, p = 0.007), as well as the individual targets of LDL ≤ 1.4, 1.0, 0.8, and 0.5 mmol/L.
When discussing the clinical implications of the study at TCT, Dr. Mehta stated: “In patients with STEMI undergoing primary PCI, routine early initiation of PCSK-9 inhibitor [in addition to high-intensity statin] reduced LDL-cholesterol by 22% at 6 weeks…and resulted in a greater proportion of patients achieving > 50% LDL reduction or the ESC LDL target…regardless of baseline LDL level or prior statin use.”