Immunomodulatory Effects of PCSK9 Inhibition

Launched by MASSACHUSETTS GENERAL HOSPITAL · Jan 30, 2023

Keywords

ClinConnect Summary

This clinical trial is studying the effects of a new type of medication called PCSK9 inhibitors on inflammation in patients with atherosclerotic cardiovascular disease (ASCVD), which is a condition that can lead to heart attacks and strokes. While existing medications like statins are effective at lowering cholesterol and reducing heart disease risk, they may not fully address inflammation in the arteries. The goal of this study is to see if PCSK9 inhibitors can not only lower cholesterol even further but also reduce inflammation in the arteries, potentially leading to better heart health.

To participate in this trial, individuals must be between the ages of 18 and 85 and have a history of ASCVD while being on high-intensity statin therapy for at least six months. Participants will receive either evolocumab or alirocumab, two types of PCSK9 inhibitors. Throughout the study, participants can expect to undergo specific imaging tests to measure inflammation in their arteries. This research is important because it aims to improve how we prevent and treat cardiovascular diseases, ultimately helping to reduce the risks associated with heart attacks and strokes.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 18 to 85 years of age
• • CASE PARTICIPANTS ONLY: History of ASCVD (including a history of coronary artery disease, carotid artery disease, peripheral artery disease, acute coronary syndrome, percutaneous coronary intervention, coronary bypass surgery, carotid endarterectomy, stroke or TIA)
• • CASE PARTICIPANTS ONLY: High-intensity statin therapy for at least 6 months prior enrollment and without an interruption of \>1 month
• • CASE PARTICIPANTS ONLY: Initiation of PCSK9 inhibition with either evolocumab or alirocumab (and not inclisiran - PSCK9 inhibition through small interfering RNA)
• Exclusion Criteria:
• • pregnancy or breastfeeding
• • CONTROL PARTICIPANTS ONLY: No known history of ASCVD (including a history of coronary artery disease, carotid artery disease, peripheral artery disease, acute coronary syndrome, percutaneous coronary intervention, coronary bypass surgery, carotid endarterectomy, stroke or TIA)
• • current treatment with prescription, systemic (oral, IV, IM or intra-articular) steroids or anti-inflammatory/immune suppressant medical therapies (excluding topical therapies, UV therapy, ASA-derivative therapies, or NSAIDS) for autoimmune/inflammatory diseases (psoriasis, RA, IBD, lupus), post-transplant care, asthma, or pain syndromes
• • use of oral steroids or prescription oral anti-inflammatory/immune suppressant medication for \> 7 days within the past 1 month
• • use of IV, IM or intra-articular steroids or IV, IM or intra-articular anti-inflammatory/immune suppressant medication within the past 3 months
• • Any prior use of PCSK9 inhibitors including both monoclonal antibodies or small interfering RNA
• • CONTROL PARTICIPANTS ONLY: use of cholesterol lowering therapy (including statins, ezetimibe, bempedoic acid, PCSK9 inhibitors including both monoclonal antibodies or small interfering RNA, niacin, fibrates) or other lipid lowering agents associated with ASCVD risk reduction such as Vascepa. Cholesterol lowering therapies that that predominantly target triglycerides including over the counter omega-3 fatty acids and Lovaza are permitted.
• • known allergy to dextrans and/or DTPA and/or radiometals
• • significant radiation exposure (\>2 CT angiograms) received within the past 12 months
• • concurrent enrollment in another research study judged by the study investigators to interfere with the current study