PCSK9 inhibitor therapy within 24 hours after PCI was shown to bring LDL-C levels down closer to guideline-recommended goals.
Early disease-onset evolocumab (Repatha) initiation was associated with rapid, safe, LDL cholesterol (LDL-C) reduction among patients with acute myocardial infarction undergoing percutaneous coronary intervention (PCI) in a new study.
In data presented virtually this weekend during the European Society of Cardiology (ESC) 2020 Congress, investigators from Japan reported findings showing administration of the PCSK9 inhibitor within a day of PCI is associated with rapid reduction in LDL-C over 4 weeks.
Investigators, led by Tomoaki Okada, MD, of the Department of Cardiology at the Kagawa Prefectural Central Hospital in Takamatsu, sought to interpret the feasibility and safety for early-initiated PCSK9 inhibitors in AMI patients undergoing primary PCI.
As they noted, recent ESC and European Atherosclerosis Society (EAS) Guidelines for the management of dyslipidemia govern that the treatment goal of LDL-C in very high-risk patients is <55 mg/dL.
“PCSK9 inhibitors in addition to strong statins could be a useful strategy for rapid and aggressive lowering of LDL-C,” they wrote.
They conducted a single-center, randomized, controlled trial including 102 patients hospitalized with AMI, enrolled between October 2017 and December 2019. Patients were randomly assigned 1:1 to either 140 mg evolocumab subcutaneous injection or control.
Therapy was provided within 24 hours post-PCI, and then every 2 weeks. Pitavastatin, 2mg daily, was included in all patients’ therapy regimen. Okada and colleagues assessed for primary endpoints in patient lipid profile change, as well as inflammatory-based improvements, from baseline to 4 weeks.
Nearly all patients (n = 89) were ST-segment elevation myocardial infarction (STEMI); the rest were non-STEMI. Three-fourths (n = 76) of patients were statin-naïve. Primary PCI was conducted successfully in all trial patients.
A pair of patients, both in the control arm, were excluded from analysis due to death from severe heart failure in acute therapy phase.
Of the remaining 100 patients in evolocumab and control arms, baseline LDL-C was 121.6±30.3 mg/dL and 124.7±33.6 mg/dL, respectively. LDL-C change among evolocumab-treated patients at 4 weeks was -92.4±33.6 mg/dL—an improvement of 75%. Among control patients, improvement was just 33.1% (47.6mg/dL improvement; 95% CI, 34.8 - 60.4, P <.001).
LDL-C levels <70 mg/dL was achieved by 96% of evolocumab patients at week 4, versus just 26.5% of control patients. The ESC/EAS guideline-recommended marker of LDL-C <55 mg/dL was reached by 92.1% of treated patients by week 2; the same rate was maintained through 4 weeks.
That said, investigators observed no significant difference in high-sensitivity C-reactive protein (P = .49) and tumor necrosis factor-alpha (P = .63) between either group, suggesting limited benefit for inflammatory markers with evolocumab.
Regarding safety, Okada and colleagues observed no adverse events associated with evolocumab.
The team concluded a combination of statin therapy and early evolocumab initiated shortly after PCI may be a highly efficacious and safe treatment for patients hospitalized with AMI.
The study, “Feasibility and safety of early initiation of a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor in patients with acute myocardial infarction undergoing primary PCI,” was presented at ESC 2020.