Suppression of Early TNF-Alpha Increase by a Single Evolocumab Dose in Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

Background

Early initiation of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-i) in patients with acute myocardial infarction (MI) may anticipate and maximize lipid-lowering benefit. Whether PCSK9 inhibition also exerts early anti-inflammatory effects in this setting remains unclear. This study aimed to evaluate the effects of early PCSK9-i administration on inflammatory markers and lipid parameters in patients with acute MI undergoing percutaneous coronary intervention (PCI).

Methods

In this randomized, prospective, single-center, open-label trial, patients with acute MI undergoing PCI were randomly assigned to receive a single upstream 140 mg subcutaneous dose of evolocumab immediately before PCI, on top of oral lipid-lowering therapy (LLT) (n = 30), or oral LLT alone (control group; n = 30). Tumor necrosis factor-alpha (TNF-α), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), and lipoprotein(a) [Lp(a)] levels were measured at baseline and during the early post-intervention phase.

Results

Baseline TNF-α values and lipid parameters were similar between the two groups. At 72 h after PCI, TNF-α levels were significantly lower in the evolocumab arm compared with controls (0.01 vs. 0.25 pg/mL; p = 0.025). Evolocumab was also associated with a greater relative reduction in LDL-C levels from baseline (-48% vs. -18%; p < 0.001) and apoB levels (-34% vs. -11%; p < 0.001). The proportion of patients achieving the LDL-C goal of <55 mg/dL at 72 h was higher in the evolocumab group than in controls (50% vs. 10%; p < 0.001). Lp(a) levels at 72 h were also lower with evolocumab (12 [10-33] vs. 28 [13.1-70] mg/dL; p = 0.032).

Conclusions

In patients with acute MI undergoing PCI, upstream administration of a single evolocumab dose was associated with suppression of the early post-intervention increase in TNF-α levels, together with rapid reductions in LDL-C, apoB, and Lp(a). These findings suggest a potential modulation of the early inflammatory response by PCSK9 inhibition in addition to its lipid-lowering effects. Larger studies are needed to confirm these observations and to determine their clinical relevance.