PCSK9 inhibitors act through plaque stabilisation not by improving coronary physiology: PACMAN-AMI trial

For this purpose, the researchers assessed QFR and 3D-QCA at baseline and one year in any non-IRA ≥2.0 mm and 3D-QCA DS% >25%. The prespecified primary endpoint was the number of patients with a mean QFR increase at one year, and the secondary endpoint was the change in 3D-QCA DS%.

The study revealed the following findings:

• Of 300 enrolled patients, 265 had a serial follow-up, of which 193 underwent serial QFR/3D-QCA analysis in 282 non-IRA.
• At one year, QFR increased in 53.2% of patients with alirocumab versus 40.4% with placebo (Δ12.8%; odds ratio 1.7).
• DS% decreased by 1.03±7.28% with alirocumab and increased by 1.70±8.27% with placebo (Δ–2.50%).

The findings revealed that treating AMI patients with the PCSK9 inhibitor alirocumab on top of rosuvastatin for one year led to significant 1.0% regression of 3D-QCA DS% versus an increase of 1.7% with placebo. The researchers observed no difference in the change in coronary physiology between treatment groups. However, compared to placebo-treated patients with a baseline QFR ≤0.95 more frequently, alirocumab showed improved coronary haemodynamics.

"A significant 1.0% angiographic stenosis regression with alirocumab treatment did not translate into a significant improvement in coronary physiology as evaluated by QFR," the researchers wrote. "Thus, PCSK9 inhibitors may rather act through plaque stabilisation than through improvement of coronary haemodynamics."

Reference:

Bär S, Kavaliauskaite R, Otsuka T, Ueki Y, Häner JD, Siontis GCM, Stortecky S, Shibutani H, Temperli F, Kaiser C, Iglesias JF, Jan van Geuns R, Daemen J, Spirk D, Engstrøm T, Lang I, Windecker S, Koskinas KC, Losdat S, Räber L. Impact of alirocumab on plaque regression and haemodynamics of non-culprit arteries in patients with acute myocardial infarction: a prespecified substudy of the PACMAN-AMI trial. EuroIntervention. 2023 Jun 21:EIJ-D-23-00201. doi: 10.4244/EIJ-D-23-00201. Epub ahead of print. PMID: 37341586.