Precision medicine versus standard of care for patients with myocardial infarction with non-obstructive coronary arteries (MINOCA): rationale and design of the multicentre, randomised PROMISE trial

Rocco Antonio Montone, Nicola Cosentino, Francesca Graziani, Riccardo Gorla, Marco Giuseppe Del Buono, Giulia La Vecchia, Riccardo Rinaldi, Giancarlo Marenzi, Antonio L Bartorelli, Federico De Marco, Luca Testa, Francesco Bedogni, Carlo Trani, Giovanna Liuzzo, Giampaolo Niccoli, Filippo Crea, Rocco Antonio Montone, Nicola Cosentino, Francesca Graziani, Riccardo Gorla, Marco Giuseppe Del Buono, Giulia La Vecchia, Riccardo Rinaldi, Giancarlo Marenzi, Antonio L Bartorelli, Federico De Marco, Luca Testa, Francesco Bedogni, Carlo Trani, Giovanna Liuzzo, Giampaolo Niccoli, Filippo Crea

Abstract

Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents about 6-8% of patients presenting with myocardial infarction (MI), and it is associated with a significant risk of mortality, rehospitalisation, and angina burden, with high associated socioeconomic costs. It is important to note that multiple mechanisms may be responsible for MINOCA. However, to date, there are few prospective clinical trials on MINOCA and the treatment of these patients is still not defined, most likely because of the multiple underlying pathogenic mechanisms. The PROMISE trial is a randomised, multicentre, prospective, superiority, phase IV trial that will include 180 MINOCA patients randomised 1:1 to a "precision-medicine approach", consisting of a comprehensive diagnostic workup and pharmacological treatment specific for the underlying cause, versus a "standard of care" approach, consisting of routine diagnostic workup and standard medical treatment for acute coronary syndrome. The aim of this study is to evaluate if the "precision-medicine approach" will improve the angina status, evaluated using the Seattle Angina Questionnaire summary score, at 12 months (primary endpoint). Secondary endpoints include the rate of major adverse cardiovascular events at 12-month follow-up, the related primary and secondary healthcare costs, and the ability of cardiac magnetic resonance to evaluate the different mechanisms of MINOCA. Of importance, the results derived from this trial may pave the way for a new pathophysiology-driven approach with cause-target therapies personalised for the mechanisms of MINOCA (ClinicalTrials.gov: NCT05122780).

Conflict of interest statement

L. Testa has served as an advisory board member and proctor for Abbott Vascular. The other authors have no conflicts of interest to declare.

Figures

Figure 1. Study flowchart.
Figure 1. Study flowchart.
ACEi: angiotensin-converting enzymes inhibitors; ACh: acetylcholine; ACS: acute coronary syndrome; ARB: angiotensin receptor blockers; CCB: calcium channel blockers; CE: contrast enhanced; CMR: cardiac magnetic resonance; DAPT: dual antiplatelet therapy; ECG: electrocardiogram; LV: left ventricle; MINOCA: myocardial infarction with non-obstructive coronary arteries; NSTE: non-ST-segment elevation; OCT: optical coherence tomography; OMT: optimal medical therapy; PCI: percutaneous coronary intervention; PE: plaque erosion; PR: plaque rupture; SAQSS: Seattle Angina Questionnaire summary score; SCAD: spontaneous coronary artery dissection; STEMI: ST-segment elevation myocardial infarction; TO: transoesophageal.
Figure 2. Detailed description of the different…
Figure 2. Detailed description of the different pharmacological approaches according to the specific aetiology underlying MINOCA.
ACEi: angiotensin-converting enzymes inhibitors; ACh: acetylcholine; AF: atrial fibrillation; ARB: angiotensin receptor blockers; CCB: calcium channel blockers; DAPT: dual antiplatelet therapy; ECG: electrocardiogram; LV: left ventricle; MINOCA: Myocardial Infarction with Non-Obstructive Coronary Arteries; OCT: optical coherence tomography; PCI: percutaneous coronary intervention; SAPT: single antiplatelet therapy.

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