Evolocumab addition to statins fails to prevent microvascular dysfunction in patients undergoing PCI

JAPAN: A recently completed study of coronary intervention published in EuroIntervention has highlighted the outcome of Evolocumab pretreatment as non-preventive for periprocedural microvascular dysfunction in patients on statin therapy before PCI.

A trial published in JAMA, " The Guass-3 Randomized Clinical Trial," advocated Evolocumab usage (compared to ezetimibe), resulting in a significant reduction of low-density lipoprotein cholesterol (LDL-C) levels after 24 weeks in patients with a history of statin intolerance relating muscle-related adverse effects. However, it was mentioned, "Further investigations are warranted to determine long-term efficacy and safety."

The use of high-intensity statins is largely supported for patients with high-risk complications of cardiovascular disease (CVD). Previous studies have mentioned the addition of Evolocumab to statins improves cardiovascular outcomes.

A study demonstrated Evolocumab outperformance compared to Ezetimive, which is more efficacious and attains lipid goals. This data is useful in treating patients with intolerance to statin therapy.

Considering the above background, an open-label EVOCATION trial was conducted by a research team led by Dr. Masaharu Ishihara, MD, Ph.D. at the Department of Cardiovascular and Renal Medicine from Hyogo College of Medicine to investigate the superiority of evolocumab pretreatment over statin therapy in preventing periprocedural microvascular dysfunction.

A total of 100 patients with a history of stable coronary artery disease indicated for PCI and having high LDL-C under statin therapy were included in the study. There were two groups: Evolocumab and the control group. The primary endpoint measured was the IMR (Microvascular Resistance Index) after PCI. Before and 24 hours after percutaneous coronary intervention (PCI), Troponin T was measured.

The key highlights of the study are:

• The Evolocumab group had 54 patients, and the control group had 46 patients.

• In the intervention group, 140 mg Evolocumab was given every two weeks before PCI for 2 to 6 weeks.

• After allocation, PCI was performed for 22.1±8.5 days.

• The geometric mean LDL-C was 94.1 mg/dl and 89.4 mg/dl at baseline in the evolocumab and control groups, respectively.

• Before PCI, the geometric mean LDL-C was 25.6 mg/dl in the Evolocumab group and 79.8 mg/dl in the control group.

• In the evolocumab group, the geometric mean IMR was 20.6 with a 95 % confidence interval : 17.2-24.6; in the control group, it was 20.6 with a 95% CI: 17.0-25.0. The p-value was 0.98.

• The geometric mean of post-PCI troponin T was 0.054, 95% CI: 0.041-0.071 ng/ml vs 0.054, 95% CI: 0.038-0.077 ng/ml with p value of 0.99 indicating no significant difference between the groups.

• There was an insignificant difference between the two groups in the incidence of major periprocedural myocardial infarction recorded as 44.4% vs. 44.2% with a p-value of 1.00.

The co-researcher Dr. Masanori Asakura from the Center for Clinical Research and Education, Hyogo College of Medicine, wrote that the background of our study was based on more potent properties of Evolocumab than statins, the latter having a role in preventing microvascular dysfunction which may cause periprocedural myocardial infarction after PCI. Evolocumab has more potent lipid-lowering properties than statins.

The researchers finally concluded that Evolocumab has good safety and tolerability profiles but does not prevent periprocedural microvascular dysfunction in patients on modern medical management with statins.

References:

• Evolocumab for prevention of microvascular dysfunction in patients undergoing percutaneous coronary intervention: the randomized, open-label EVOCATION trial EuroIntervention 2022;18:e647-e655.

• Nissen SE, Stroes E, Dent-Acosta RE, et al. Efficacy and Tolerability of Evolocumab vs. Ezetimibe in Patients With Muscle-Related Statin Intolerance: The GAUSS-3 Randomized Clinical Trial. JAMA. 2016;315(15):1580–1590.

• Koren, M.J., Jones, P.H., Robinson, J.G. et al. A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies. Cardiol Ther 9, 447–465 (2020).