Alirocumab addition to statins fails to improve endothelial function in acute MI patients: PACMAN-AMI trial substudy

The research, published in the Atherosclerosis journal, found no further improvement of flow-mediated dilation (FMD) with the addition of alirocumab among patients with acute myocardial infarction (AMI) than 52 weeks of secondary preventative medical therapy, including high-intensity statin therapy. FMD was significantly associated with baseline coronary plaque burden, but not lipid pool or fibrous cap thickness.

Myocardial infarction, commonly known as a heart attack, is a life-threatening condition characterized by the interruption of blood flow to the heart muscle, usually due to the obstruction of a coronary artery by a blood clot. Following a heart attack, patients are at increased risk of recurrent cardiovascular events, including further heart attacks and stroke, making effective secondary prevention strategies imperative.

Alirocumab, a monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), has garnered attention as a potential therapeutic agent for reducing low-density lipoprotein cholesterol (LDL-C) levels and lowering the risk of cardiovascular events.

Emrush Rexhaj, Department of Cardiology, Bern University Hospital Inselspital, Freiburgstrasse, Bern, Switzerland, and colleagues aimed to examine the effects of the PCSK9 inhibitor alirocumab added to high-intensity statin on FMD. They also investigated its association with coronary atherosclerosis in non-infarct-related arteries using near-infrared spectroscopy (NIRS), intracoronary intravascular ultrasound (IVUS), and optical coherence tomography (OCT).

For this purpose, the researchers conducted a pre-specified substudy among patients recruited at Bern University Hospital, Switzerland, for the randomized-controlled, double-blind, PACMAN-AMI trial that compared the effects of biweekly alirocumab 150 mg versus placebo added to rosuvastatin. At 4 and 52 weeks, brachial artery FMD was measured, and intracoronary imaging at baseline and 52 weeks.

The researchers reported the following findings:

• 139/173 patients completed the substudy. There was no difference in FMD at 52 weeks in the alirocumab (n = 68, 5.44 ± 2.24%) versus placebo (n = 71, 5.45 ± 2.19%) group (difference = −0.21%).
• FMD improved throughout 52 weeks in both groups similarly.
• There was a significant association between 4 weeks FMD and baseline plaque burden (IVUS) (n = 139, slope = −1.00), but not with lipid pool (NIRS) (n = 139, slope = −7.36), or fibrous cap thickness (OCT) (n = 81, slope = −1.57).

The study revealed improvement in endothelial function as evaluated by brachial artery FMD achieved throughout one year with guideline-based secondary preventative medical therapy, including a high-intensity statin in patients with AMI. However, adding PCSK9 inhibitor alirocumab did not further improve endothelial function.

FMD was significantly inversely related to non-infarct related arteries (non-IRA) intracoronary plaque burden before treatment initiation, but not to lipid pool or fibrous cap thickness.

Reference:

Rexhaj E, Bär S, Soria R, Ueki Y, Häner JD, Otsuka T, Kavaliauskaite R, Siontis GC, Stortecky S, Shibutani H, Spirk D, Engstrøm T, Lang I, Morf L, Ambühl M, Windecker S, Losdat S, Koskinas KC, Räber L; PACMAN-AMI Investigators. Effects of alirocumab on endothelial function and coronary atherosclerosis in myocardial infarction: A PACMAN-AMI randomized clinical trial substudy. Atherosclerosis. 2024 May;392:117504. doi: 10.1016/j.atherosclerosis.2024.117504. Epub 2024 Mar 6. PMID: 38513436.