PRediction of acute coronary syndrome in acute ischemic StrokE (PRAISE) - protocol of a prospective, multicenter trial with central reading and predefined endpoints

Christian H Nolte, Regina von Rennenberg, Simon Litmeier, Jan F Scheitz, David M Leistner, Stephan Blankenberg, Martin Dichgans, Hugo Katus, Gabor C Petzold, Burkert Pieske, Vera Regitz-Zagrosek, Karl Wegscheider, Andreas M Zeiher, Ulf Landmesser, Matthias Endres, Christian H Nolte, Regina von Rennenberg, Simon Litmeier, Jan F Scheitz, David M Leistner, Stephan Blankenberg, Martin Dichgans, Hugo Katus, Gabor C Petzold, Burkert Pieske, Vera Regitz-Zagrosek, Karl Wegscheider, Andreas M Zeiher, Ulf Landmesser, Matthias Endres

Abstract

Background: Current guidelines recommend measurement of troponin in acute ischemic stroke (AIS) patients. In AIS patients, troponin elevation is associated with increased mortality and worse outcome. However, uncertainty remains regarding the underlying pathophysiology of troponin elevation after stroke, particularly regarding diagnostic and therapeutic consequences. Troponin elevation may be caused by coronary artery disease (CAD) and more precisely acute coronary syndrome (ACS). Both have a high prevalence in stroke patients and contribute to poor outcome. Therefore, better diagnostic algorithms are needed to identify those AIS patients likely to have ACS or other manifestations of CAD.

Methods/design: The primary goal of the "PRediction of Acute coronary syndrome in acute Ischemic StrokE" (PRAISE) study is to develop a diagnostic algorithm for prediction of ACS in AIS patients. The primary hypothesis will test whether dynamic high-sensitivity troponin levels determined by repeat measurements (i.e., "rise or fall-pattern") indicate presence of ACS when compared to stable (chronic) troponin elevation. PRAISE is a prospective, multicenter, observational trial with central reading and predefined endpoints guided by a steering committee. Clinical symptoms, troponin levels as well as findings on electrocardiogram, echocardiogram, and coronary angiogram will be recorded and assessed by central academic core laboratories. Diagnosis of ACS will be made by an endpoint adjudication committee. Severe adverse events will be evaluated by a critical event committee. Safety will be judged by a data and safety monitoring board. Follow-up will be conducted at three and twelve months and will record new vascular events (i.e., stroke and myocardial infarction) as well as death, functional and cognitive status. According to sample size calculation, 251 patients have to be included.

Discussion: PRAISE will prospectively determine the frequency of ACS and characterize cardiac and coronary pathologies in a large, multicenter cohort of AIS patients with troponin elevation. The findings will elucidate the origin of troponin elevation, shed light on its impact on necessary diagnostic procedures and provide data on the safety and diagnostic yield of coronary angiography early after stroke. Thereby, PRAISE will help to refine algorithms and develop guidelines for the cardiac workup in AIS.

Trial registration: NCT03609385 registered 1st August 2018.

Keywords: Acute coronary syndrome; Acute ischemic stroke; Chronic coronary disease; Heart-and-brain interaction; Stroke-heart-syndrome; Troponin elevation.

Conflict of interest statement

ME reports grants from Bayer and fees paid to the Charité from Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Amgen, GSK, Sanofi, Covidien, Novartis, Pfizer, all outside the submitted work. CHN reports lecture fees and/or consultancies from Boehringer Ingelheim, BMS, Daiichi Sankyo, Sanofi, Pfizer, Abbott and Gore & Ass..

Figures

Fig. 1
Fig. 1
shows the study flow chart and visualizes the primary endpoint assessment and follow-up. ACS = acute coronary syndrome, ECG = electrocardiography, MI = myocardial infarction, TIA = transient ischemic attack

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