Early TNF-alpha levels suppression by upstream evolocumab use in patients with acute myocardial infarction undergoing percutaneous coronary intervention

Introduction A strong low-density lipoprotein cholesterol (LDL-C) reduction with proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) reduces the residual risk in patients with myocardial infarction (MI). Recent data suggested that PCSK9i could be early initiated in patients with acute MI to maximize their clinical benefit; here pleiotropic effects (e.g. anti-inflammatory effects), beside the lipid-lowering action, were hypothesized, but there is no available evidence on this topic. Methods We evaluated an upstream use of evolocumab on inflammation and lipid levels in patients with acute MI undergoing percutaneous coronary intervention (PCI). Participants were randomized to receive either a single 140 mg s.c. dose of evolocumab prior to PCI (typically as soon as possible upon hospital admission) on top of oral lipid-lowering therapy (LLT) or oral LLT alone (control group). TNF-alpha, LDL-C and ApoB levels were measured at baseline and at 24 and 72 hours post-intervention. The following primary outcomes were considered at 72 hours: post-procedural changes of TNF-alpha, LDL-C and ApoB levels; percentage of patients achieving an LDL-C value <55 mg/dL. Results A total of 60 patients were enrolled (n=30 in each arm). Baseline characteristics, including demographic features, comorbidities, lipid profile and background LLT, were similar in the two groups. At 72 hours after PCI, in the evolocumab arm, TNF-alpha levels were significantly lower (0.01 pg/mL vs. 0.25 pg/mL in controls; p=0.025), a greater relative reduction for both LDL-C (-48% vs. -18%, p<0.001) and ApoB levels (-34% vs. -11%, p<0.001) was observed, and the percentage of LDL-C goal achievement was higher (50% vs. 10%, p<0.001). Conclusion Our study for the first time shows that an upstream evolocumab use in patients with acute MI undergoing PCI is associated with an early reduction of the TNF-alpha pro-inflammatory marker and a prompt improvement of the lipid profile, in terms of LDL-C and ApoB levels decrease.