Background: The risk for cardiovascular adverse events after acute myocardial infarction (AMI) remains high despite potent medical treatment including low-density lipoprotein cholesterol (LDL-C) lowering with statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies substantially reduce LDL-C when added to statin. Alirocumab, a monoclonal antibody to PCSK9, reduces major adverse cardiovascular events after AMI. The effects of alirocumab on coronary atherosclerosis including plaque burden, plaque composition and fibrous cap thickness in patients presenting with AMI remains unknown. Aims: To determine the effect of LDL-C lowering with alirocumab on top of high-intensity statin therapy on intravascular ultrasound (IVUS)-derived percent atheroma volume (PAV), near-infrared spectroscopy (NIRS)-derived maximum lipid core burden index within 4 mm (maxLCBI4 mm) and optical coherence tomography (OCT)-derived fibrous cap thickness (FCT) in patients with AMI. Methods: In this multicenter, double-blind, placebo-controlled trial, 300 patients with AMI (ST-elevation or non-ST-elevation myocardial infarction) were randomly assigned to receive either biweekly subcutaneous alirocumab (150 mg) or placebo beginning <24 hours after the acute event as add-on therapy to rosuvastatin 20 mg. Patients undergo serial IVUS, NIRS and OCT in the two non-infarct related arteries at baseline (at the time of treatment of the culprit lesion) and at 52 weeks. The primary endpoint, change in IVUS-derived PAV, and the powered secondary endpoints, change in NIRS-derived maxLCBI4 mm, and OCT-derived minimal FCT, will be assessed 52 weeks post randomization. The PACMAN-AMI trial will determine the effect of alirocumab on top of high-intensity statin therapy on high-risk coronary plaque characteristics as assessed by serial, multimodality intracoronary imaging in patients presenting with AMI. Clinical trial registration: NCT03067844
Bibliographical noteFunding Information:
The study is supported by a grant to Bern University Hospital provided by Regeneron, Sanofi, and Infraredx. The grant providers were not involved in protocol writing, data acquisition, storage and analysis. Regeneron provided alirocumab and the matching placebo free of charge. One employee of Sanofi (DS) contributed to the trial conception, and also provided expertise on the investigational medicinal product, study material, and drug-related assay and equipment.
KCK received research grants to the institution by Amgen and consultation or speaker fees by Amgen and Sanofi. SB reports a research grant to the institution from Medis Medical Imaging Systems. JD received institutional grant/research support from Astra Zeneca, Abbott Vascular, Boston Scientific, ACIST Medical, Medtronic, Pie Medical, and ReCor medical, and consultancy and speaker fees from Abiomed, ACIST medical, Boston Scientific, PulseCath, ReCor Medical, Pie Medical and Medtronic. CMM received research grants to the institution by Sanofi, Swiss Heart Foundation and Swiss National Science Foundation and consultation or speaker fees by Novartis, Daiichi Sankyo and MSD. CMM is a paid member of the section careers of the Swiss National Science Foundation. DS is an employee of Sanofi. TE has received speakers/advisory board fee from Abbott Vascular, Boston Scientific, Bayer, Novo Nordisk. SB reports a research grant to the institution from Medis Medical Imaging Systems. SW reports research and educational grants to the institution from Abbott, Amgen, BMS, Bayer, Boston Scientific, Biotronik, Cardinal Health, CardioValve, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Johnson&Johnson, Medtronic, Querbet, Polares, Sanofi, Terumo, Sinomed. SW serves as unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, BMS, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Sinomed, V-Wave and Xeltis, but has not received personal payments by pharmaceutical companies or device manufacturers. He is also member of the steering/executive committee group of several investigated-initiated trials that receive funding by industry without impact on his personal remuneration. SW is an unpaid member of the Pfizer Research Award selection committee in Switzerland. LR has received research grants to the institution by Abbott Vascular, Biotronik, BostonScientific, Heartflow, Sanofi, and Regeneron and consultation or speaker fees by Abbott vascular, Abbott structural, AstraZeneca, Amgen, Canon, Infraredx, Sanofi, Vifor. RvG received research grants to the institution by AstraZeneca, Amgen and InfraRedx. All other authors don't report any conflict of interest.