Effect of platelet inhibition and / or Lipid lowering in non-ACS-patients with acute chest pain, and high-sensitivity troponin values above the 99th percentile (GRAY-ZONE)
Final Report Abstract
Burden of cardiovascular disease in Western societies is tremendous. Acute coronary syndrome (ACS) is a clearly defined entity, with high sensitive (hs) troponin being a key element of diagnosis. Nevertheless, it is not clear, whether subjects presenting with acute symptoms and troponin levels at/above the 99th percentile, who are not classified as having an ACS, suffer from underlying myocardial ischemia. Pathophysiological data show that in these cases elevated Tn levels indicate underlying ischemia, and these subjects may benefit from platelet inhibition. Our databases show, that hs troponin levels above the 99th percentile in patients presenting with chest pain are indicative for future cardiovascular events, even when ACS was ruled out (Eventrate in 3 distinct prospective registries between 15 and 22% within 180 to 450 days). The vast majority of these non-ACS-patients is discharged without specific / preventive (antiplatelet or anti-lipid) therapy. We assumed, based on our own multi-center registry data that each year around 400,000 subjects in Germany might be affected. We proposed that platelet inhibition by Acetylsalicylic acid (ASA) or lipid lowering by Statin could prevent plaque rupture and superimposition of thrombosis to coronary atherosclerosis in this population. Medical profession is still so familiarized with current triage models, that the attitude would only be changed with a randomized trial showing clear clinical benefit. GrayZone was a controlled clinical trial: up to 3,000 troponin positive patients presenting at emergency room (ER)/CPU with symptoms suggestive for ACS, in whom an ACS was ruled out, were planned to be assigned randomly to ASA and/or Statin versus placebo (2x2 factorial design). However, shortly after the initiation of the study in February 2020, we were forced to deal with the COVID-19-pandemic-related lockdowns, which caused an unprecedented disruption of the public life and resulted in significant challenges to all clinical trial operations. Multiple industrial and academic sponsors announced recruitment halts and new trial initiations had been delayed to ensure health and safety of the participants and clinical trial site teams. In line, recruitment into the GrayZone trial at sponsor’s and other study sites were extremely reduced and the recruitment and initiation of others was halted. In addition, as reported by various working groups, the number of cardiovascular patients in general, but especially those presenting at emergency department and chest pain units strongly decreased. In line, Medidata has reported a striking overall 75% decrease in the number of new patients entering trials with the hardest hit in cardiovascular therapeutic area where a 95% decrease was noted. This effect was most pronounced for “low-risk” populations, as in our prevention study. Our calculations revealed that successful completion of the study would not have been achieved before 2027 to 2029. Therefore, the study was preliminary terminated on December 20th, 2021 with 68 randomized patients. Due to the low recruitment numbers no statistical evaluation of efficacy was performed but a descriptive overview of the collected data is given. Nevertheless, the topic of this study is still of great importance and therefore, we plan to further investigate this issue in a new de-centralised approach.
