Comparative effects of fentanyl versus morphine on platelet inhibition induced by ticagrelor in patients with ST-segment elevation myocardial infarction: Full results of the PERSEUS randomized trial.

"Conflict of interest: Juan F. Iglesias reports research grants to the institution and personal fees from AstraZeneca during the conduct of the study; grants and personal fees from Biotronik, Philips Volcano, and AstraZeneca, and personal fees from Terumo, Medtronic, and Cardinal Health, outside the submitted work; Marco Valgimigli reports grants and personal fees from Abbott, Terumo, and AstraZeneca, personal fees from Bayer, Daiichi Sankyo, Amgen, Alvimedica, Idorsia, Coreflow, Vifor, Bristol-Myers Squibb, and iVascular, and grants from Medicare, outside the submitted work; Sophie Degrauwe reports grants and personal fees from Biotronik, outside the submitted work. All other authors declare no conflicts of interest."

"Funding"

"PERSEUS was an investigator-initiated, prospective, single-center, open-label, randomized controlled trial. A detailed description of the study rationale and design has been previously published []. Briefly, patients with STEMI undergoing primary PCI within 12 hours of symptoms’ onset were eligible for inclusion. Key inclusion and exclusion criteria have been reported previously []. Patients on chronic P2Y12 receptor antagonist or oral anticoagulation therapy, or who received glycoprotein IIb/IIIa inhibitors were excluded. In addition, patients with medical conditions that may adversely affect gastrointestinal absorption and metabolic activation of oral P2Y12 receptor inhibitors, including comatose patients or those with cardiogenic shock, were excluded. All patients were pre-treated with ASA (loading dose [LD] 500 mg), ticagrelor (LD 180 mg), and unfractionated heparin (LD 5000 IU or 70–100 IU per kg of body weight) at the time of STEMI diagnosis. Patients requiring analgesia for pain relief (visual analogue scale [VAS] score ≥ 3) were randomly assigned in a 1:1 ratio to treatment with intravenous fentanyl (50–100 μg) or morphine (4–8 mg) using a centralized telephone treatment allocation. Additional doses of fentanyl (25 μg, every 2–5 min) or morphine (2 mg, every 5–15 min) were administrated to achieve adequate analgesia (VAS score < 3). All patients underwent primary PCI according to institutional standards. The choice of vascular access site, periprocedural anticoagulation regimen, and procedural techniques was left to the discretion of the treating physician. After primary PCI, all patients received a maintenance dose of ASA (100 mg daily) indefinitely. A ticagrelor maintenance dose (90 mg twice daily) was initiated 12 hours after the LD and was recommended for at least 12 months. The study protocol complied with the Declaration of Helsinki. The study protocol was approved by the local Ethics Committee at Lausanne University Hospital, Switzerland (Project ID: PB_2016-00291). All enrolled patients provided written informed consent for participation. The trial was registered with ClinicalTrials.gov, identifier NCT02531165."