Anticoagulation and Antiplatelet Therapy for Prevention of Venous and Arterial Thrombotic Events in Critically Ill Patients With COVID-19: COVID-PACT

Erin A. Bohula, David D. Berg, Mathew S. Lopes, Jean M. Connors, Ijlal Babar, Christopher F. Barnett, Sunit Preet Chaudhry, Amit Chopra, Wilson Ginete, Michael H. Ieong, Jason N. Katz, Edy Y. Kim, Julia F. Kuder, Emilio Mazza, Dalton McLean, Jarrod M. Mosier, Ari Moskowitz, Sabina A. Murphy, Michelle L. O'Donoghue, Jeong Gun ParkRajnish Prasad, Christian T. Ruff, Mohamad N. Shahrour, Shashank S. Sinha, Stephen D. Wiviott, Sean Van Diepen, Mark Zainea, Vivian Baird-Zars, Marc S. Sabatine, David A. Morrow, Kyung Ah Im, Retu Saxena, Brandon Wiley, Carina Benson, Roman Delamed, Nedaa Skeik, Ami Chopra, Marc Judson, Scott Beegle, Boris Shkolnik, Anupama Tiwari, Gregory Wu, Abhijit Raval, Emerald Branch, Franz Rischard, Cameron Hypes, Billie Bixby, Christian Bime, Madhan Sundaram, Nancy Sweitzer, Alfredo Vazquez Sandoval, Heath White, Katherine Berg, Shahzad Shaefi, Michael Donnino, Brett Carroll, Michael Ieong, Kimberly Ackerbauer, Jaime Murphy, Ankeet Bhatt, Alexander Blood, Siddharth Patel, Victor Luu, Shraddha Narechania, Austin Lorganger, Robert Plambeck, Ali Nayfeh, Michael Sanley, Michel Del Cor, A. J. Hegg, Winston Nara, Michael Snyder, Faisal Khan, Imad Shawa, Joshua Larned, Elias Collado, Mohammed Al Faiyumi, Rajeev Mehta, Sudarshan Komanapalli, Vijayadershan Muppidi, Mehul Desai, Casey Flanagan, Leonard Genovese, Tariq Haddad, Christopher King, Amber Peterson, Thane Htun, Elizabeth Pionk, Nicolas Mouawad, Chintalapudi Kumar, Kevin Nguyen, Majid Mughal, Ryan Malek, Akarsh Parekh, Christopher Provenzano, Melissa Ianitelli, Nicole Prentice-Gaytan, Adam Bykowski, Don Tait, Shelley Schendel, Varun Yalamanchili, Vasim Lala, Victor Hunyadi, Alexander Papolos, Benjamin Kenigsberg, Aarthi Shenoy, Thomas Stuckey, Douglas McQuaid, Praveen Mannam, Jeffrey McClung, Kent Nilsson, Andrew McKown, Jason Wells, David Hotchkin, Marc Jacobs, Wayne Strauss, Rick Balestra, Vikram Sahni, R. Jeffrey Snell, Hussam Suradi, Sarah Sungurlu, Jessica Kuppy, Eileen Gajo, Foster Adams, Abbas Shehadeh, Addi Suleiman, Harish Nandigam, Jihad Slim, Sardar Ijlal Babar, Dipti Baral, Talha Nawaz, Syed Abdullah Waheed, Randy Roth, Subhas Sitaula, Shahid Hayat, Jooby Babu, Jason Caberto, Victor Hsu, Robert Chang, Markian Bochan, Rafael Garcia-Cortes, Hal Skopicki, On Chen, Lauren Pilato, Paul Richman, Alexander Adler, Praveen Sudhindra, Jamie Beversdorf, Ravindra Kashyap, Parth Mehta, Borna Mehrad, Ali Ataya, Jorge Lascano, Mark Brantly, Adam Austin, Eduard Koman, Thomas Galski, Vijaya Kumar, Ayman Soubani, Nicolas Harrison, Vineet Reddy, Audrey Fonkam

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Background: The efficacy and safety of prophylactic full-dose anticoagulation and antiplatelet therapy in critically ill COVID-19 patients remain uncertain. Methods: COVID-PACT (Prevention of Arteriovenous Thrombotic Events in Critically-ill COVID-19 Patients Trial) was a multicenter, 2×2 factorial, open-label, randomized-controlled trial with blinded end point adjudication in intensive care unit-level patients with COVID-19. Patients were randomly assigned to a strategy of full-dose anticoagulation or standard-dose prophylactic anticoagulation. Absent an indication for antiplatelet therapy, patients were additionally randomly assigned to either clopidogrel or no antiplatelet therapy. The primary efficacy outcome was the hierarchical composite of death attributable to venous or arterial thrombosis, pulmonary embolism, clinically evident deep venous thrombosis, type 1 myocardial infarction, ischemic stroke, systemic embolic event or acute limb ischemia, or clinically silent deep venous thrombosis, through hospital discharge or 28 days. The primary efficacy analyses included an unmatched win ratio and time-to-first event analysis while patients were on treatment. The primary safety outcome was fatal or life-threatening bleeding. The secondary safety outcome was moderate to severe bleeding. Recruitment was stopped early in March 2022 (≈50% planned recruitment) because of waning intensive care unit-level COVID-19 rates. Results: At 34 centers in the United States, 390 patients were randomly assigned between anticoagulation strategies and 292 between antiplatelet strategies (382 and 290 in the on-treatment analyses). At randomization, 99% of patients required advanced respiratory therapy, including 15% requiring invasive mechanical ventilation; 40% required invasive ventilation during hospitalization. Comparing anticoagulation strategies, a greater proportion of wins occurred with full-dose anticoagulation (12.3%) versus standard-dose prophylactic anticoagulation (6.4%; win ratio, 1.95 [95% CI, 1.08-3.55]; P=0.028). Results were consistent in time-to-event analysis for the primary efficacy end point (full-dose versus standard-dose incidence 19/191 [9.9%] versus 29/191 [15.2%]; hazard ratio, 0.56 [95% CI, 0.32-0.99]; P=0.046). The primary safety end point occurred in 4 (2.1%) on full dose and in 1 (0.5%) on standard dose (P=0.19); the secondary safety end point occurred in 15 (7.9%) versus 1 (0.5%; P=0.002). There was no difference in all-cause mortality (hazard ratio, 0.91 [95% CI, 0.56-1.48]; P=0.70). There were no differences in the primary efficacy or safety end points with clopidogrel versus no antiplatelet therapy. Conclusions: In critically ill patients with COVID-19, full-dose anticoagulation, but not clopidogrel, reduced thrombotic complications with an increase in bleeding, driven primarily by transfusions in hemodynamically stable patients, and no apparent excess in mortality. Registration: URL:; Unique identifier: NCT04409834.

Original languageEnglish (US)
Pages (from-to)1344-1356
Number of pages13
Issue number18
StatePublished - Nov 1 2022


  • COVID-19
  • anticoagulants
  • clopidogrel
  • hemorrhage
  • platelet aggregation inhibitors
  • thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


Dive into the research topics of 'Anticoagulation and Antiplatelet Therapy for Prevention of Venous and Arterial Thrombotic Events in Critically Ill Patients With COVID-19: COVID-PACT'. Together they form a unique fingerprint.

Cite this