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Randomized Controlled Trial
. 2023 Aug;21(8):2213-2222.
doi: 10.1016/j.jtha.2023.04.045. Epub 2023 May 23.

A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial

Prapa Kanagaratnam  1 , Darrel P Francis  2 , Daniel Chamie  3 , Clare Coyle  2 , Alena Marynina  4 , George Katritsis  4 , Patricia Paiva  3 , Matyas Szigeti  5 , Graham Cole  2 , David de Andrade Nunes  3 , James Howard  2 , Rodrigo Esper  6 , Masood Khan  7 , Ranjit More  8 , Guilherme Barreto  9 , Rafael Meneguz-Moreno  10 , Ahran Arnold  2 , Alexandra Nowbar  4 , Amit Kaura  2 , Myril Mariveles  4 , Katherine March  4 , Jaymin Shah  11 , Sukhjinder Nijjer  12 , Gregory Y H Lip  13 , Nicholas Mills  14 , A John Camm  15 , Graham S Cooke  2 , Simon J Corbett  16 , Martin J Llewelyn  17 , Waleed Ghanima  18 , Mark Toshner  19 , Nicholas Peters  2 , Ricardo Petraco  2 , Rasha Al-Lamee  2 , Ana Sousa Marcelino Boshoff  20 , Margarita Durkina  20 , Iqbal Malik  2 , Neil Ruparelia  21 , Victoria Cornelius  20 , Matthew Shun-Shin  22
Affiliations
Randomized Controlled Trial

A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial

Prapa Kanagaratnam et al. J Thromb Haemost. 2023 Aug.

Abstract

Background: Patients hospitalized with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease.

Objectives: To investigate the efficacy of an acute coronary syndrome regimen in patients hospitalized with COVID-19 and coronary disease risk factors.

Methods: A randomized controlled, open-label trial across acute hospitals (United Kingdom and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28 days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, or death).

Results: Three hundred twenty patients from 9 centers were randomized. The trial terminated early due to low recruitment. At 30 days, there was no significant difference in mortality (intervention vs control, 11.5% vs 15%; unadjusted odds ratio [OR], 0.73; 95% CI, 0.38-1.41; p = .355). Significant bleeds were infrequent and were not significantly different between the arms (intervention vs control, 1.9% vs 1.9%; p > .999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR, 1.46; 95% credible interval [CrI], 0.88-2.37; Pr [beta > 0], 93%; adjusted OR, 1.50; 95% CrI, 0.91-2.45; Pr [beta > 0], 95%) and median time to discharge to home was 2 days shorter (95% CrI, -4 to 0; 2% probability that it was worse).

Conclusion: Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality.

Keywords: COVID-19 infection; anticoagulant agent; antiplatelet agent; ischemic heart disease; randomized controlled trial; thrombosis.

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Conflict of interest statement

Declaration of competing interests P.K. receives research grants and consulting fees from Biosense-Webster, Abbott-Medical, Medtronic, and Boston Scientific. A patent for Ripple Mapping is licensed to Biosense-Webster, and royalties are paid to Imperial College. C.C. is the recipient of a British Heart Foundation Clinical Research Training Fellowship (number FS/20/14/34917). A.A. has had support to attend conferences from Bayer. A.N. received a research grant from the NIHR Academy. S.N. received payment or honoraria for speaker events/presentations from Bayer, Pfizer, and Philips and participates on an Advisory Board for Astra Zeneca. G.Y.H.L. is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, and Daiichi Sankyo. No fees are received personally. N.M. is supported by a Chair Award, Program Grant, and Research Excellence Award (CH/F/21/90010, RG/20/10/34966, and RE/18/5/34216, respectively) from the British Heart Foundation. A.J.C. reports personal fees/consulting fees from Bayer, Pfizer, BMS, Daiichi Sankyo, and Boehringer Ingelheim; reports royalties and/or editorial fees from Oxford University Press, Wiley, and Springer Verlag; and participates on DSMBs/Advisory Boards at Biotronik, Johnson and Johnson, and Allergan. G.S.C. receives grants from the NIHR, participates on DSMBs, and is a nonexecutive director at the MHRA. W.G. reports fees for participation in Advisory Board from Amgen, Novartis, Pfizer, Principia Biopharma Inc—a Sanofi Company, Sanofi, SOBI, Grifols, UCB, Argenx, Cellphire, and Hutchmed; lecture honoraria from Amgen, Novartis, Pfizer, Bristol Myers Squibb, SOBI, Grifols, and Sanofi; and research grants from Bayer and BMS/Pfizer. M.T. reports Scientific Advisory Board personal fees from MorphogenIX and personal fees/honoraria from J&J/Actelion. R.A.-L. receives speaker’s honoraria from Philips Volcano, Medtronic, and Menarini. M.S.-S. has received honoraria from Pfizer (<£500). D.P.F., D.C., A.M., G.K., P.P., M.S., G.C., D.d.A.N., J.H., R.E., M.K., R.M., G.B., R.M.M., A.K., M.M., K.M., J.S., S.J.C., M.J.L., N.P., R.P., A.S.M.B., M.D., I.M., N.P., V.C. have no competing interests to disclose.

Figures

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Graphical abstract
Figure 1
Figure 1
CONSORT diagram.
Figure 2
Figure 2
The proportion of participants in each of the 4 clinical states, split by the active and control arms (pairs of columns, active left and control right), over the 30 days after randomization. ICU, intensive care unit.
See this image and copyright information in PMC

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