Anticoagulation and Antiplatelet Therapy for Prevention of Venous and Arterial Thrombotic Events in Critically Ill Patients With COVID-19: COVID-PACT. Issue 18 (29th August 2022)

• Record Type: Journal Article
• Authors: Bohula, Erin A.; Berg, David D.; Lopes, Mathew S.; Connors, Jean M.; Babar, Ijlal; Barnett, Christopher F.; Chaudhry, Sunit-Preet; Chopra, Amit; Ginete, Wilson; Ieong, Michael H.; Katz, Jason N.; Kim, Edy Y.; Kuder, Julia F.; Mazza, Emilio; McLean, Dalton; Mosier, Jarrod M.; Moskowitz, Ari; Murphy, Sabina A.; O'Donoghue, Michelle L.; Park, Jeong-Gun; Prasad, Rajnish; Ruff, Christian T.; Shahrour, Mohamad N.; Sinha, Shashank S.; Wiviott, Stephen D.; Van Diepen, Sean; Zainea, Mark; Baird-Zars, Vivian; Sabatine, Marc S.; Morrow, David A.
• Other Names: Im Kyung Ah author non-byline.; Saxena Retu author non-byline.; Wiley Brandon author non-byline.; Benson Carina author non-byline.; Delamed Roman author non-byline.; Skeik Nedaa author non-byline.; Chopra Ami author non-byline.; Judson Marc author non-byline.; Beegle Scott author non-byline.; Shkolnik Boris author non-byline.; Tiwari Anupama author non-byline.; Wu Gregory author non-byline.; Raval Abhijit author non-byline.; Branch Emerald author non-byline.; Rischard Franz author non-byline.; Hypes Cameron author non-byline.; Bixby Billie author non-byline.; Bime Christian author non-byline.; Sundaram Madhan author non-byline.; Sweitzer Nancy author non-byline.; Sandoval Alfredo Vazquez author non-byline.; White Heath author non-byline.; Berg Katherine author non-byline.; Shaefi Shahzad author non-byline.; Donnino Michael author non-byline.; Carroll Brett author non-byline.; Ieong Michael author non-byline.; Ackerbauer Kimberly author non-byline.; Murphy Jaime author non-byline.; Bhatt Ankeet author non-byline.; Blood Alexander author non-byline.; Patel Siddharth author non-byline.; Luu Victor author non-byline.; Narechania Shraddha author non-byline.; Lorganger Austin author non-byline.; Plambeck Robert author non-byline.; Nayfeh Ali author non-byline.; Sanley Michael author non-byline.; Del Cor Michel author non-byline.; Hegg AJ author non-byline.; Nara Winston author non-byline.; Snyder Michael author non-byline.; Khan Faisal author non-byline.; Shawa Imad author non-byline.; Larned Joshua author non-byline.; Collado Elias author non-byline.; Al Faiyumi Mohammed author non-byline.; Mehta Rajeev author non-byline.; Komanapalli Sudarshan author non-byline.; Muppidi Vijayadershan author non-byline.; Desai Mehul author non-byline.; Flanagan Casey author non-byline.; Genovese Leonard author non-byline.; Haddad Tariq author non-byline.; King Christopher author non-byline.; Peterson Amber author non-byline.; Htun Thane author non-byline.; Pionk Elizabeth author non-byline.; Mouawad Nicolas author non-byline.; Kumar Chintalapudi author non-byline.; Nguyen Kevin author non-byline.; Mughal Majid author non-byline.; Malek Ryan author non-byline.; Parekh Akarsh author non-byline.; Provenzano Christopher author non-byline.; Ianitelli Melissa author non-byline.; Prentice-Gaytan Nicole author non-byline.; Bykowski Adam author non-byline.; Tait Don author non-byline.; Schendel Shelley author non-byline.; Yalamanchili Varun author non-byline.; Lala Vasim author non-byline.; Hunyadi Victor author non-byline.; Papolos Alexander author non-byline.; Kenigsberg Benjamin author non-byline.; Shenoy Aarthi author non-byline.; Stuckey Thomas author non-byline.; McQuaid Douglas author non-byline.; Mannam Praveen author non-byline.; McClung Jeffrey author non-byline.; Nilsson Kent author non-byline.; McKown Andrew author non-byline.; Wells Jason author non-byline.; Hotchkin David author non-byline.; Jacobs Marc author non-byline.; Strauss Wayne author non-byline.; Balestra Rick author non-byline.; Sahni Vikram author non-byline.; Snell R. Jeffrey author non-byline.; Suradi Hussam author non-byline.; Sungurlu Sarah author non-byline.; Kuppy Jessica author non-byline.; Gajo Eileen author non-byline.; Adams Foster author non-byline.; Shehadeh Abbas author non-byline.; Suleiman Addi author non-byline.; Nandigam Harish author non-byline.; Slim Jihad author non-byline.; Babar Sardar Ijlal author non-byline.; Baral Dipti author non-byline.; Nawaz Talha author non-byline.; Waheed Syed Abdullah author non-byline.; Roth Randy author non-byline.; Sitaula Subhas author non-byline.; Hayat Shahid author non-byline.; Babu Jooby author non-byline.; Caberto Jason author non-byline.; Hsu Victor author non-byline.; Chang Robert author non-byline.; Bochan Markian author non-byline.; Garcia-Cortes Rafael author non-byline.; Skopicki Hal author non-byline.; Chen On author non-byline.; Pilato Lauren author non-byline.; Richman Paul author non-byline.; Adler Alexander author non-byline.; Sudhindra Praveen author non-byline.; Beversdorf Jamie author non-byline.; Kashyap Ravindra author non-byline.; Mehta Parth author non-byline.; Mehrad Borna author non-byline.; Ataya Ali author non-byline.; Lascano Jorge author non-byline.; Brantly Mark author non-byline.; Austin Adam author non-byline.; Koman Eduard author non-byline.; Galski Thomas author non-byline.; Kumar Vijaya author non-byline.; Soubani Ayman author non-byline.; Harrison Nicolas author non-byline.; Reddy Vineet author non-byline.; Fonkam Audrey author non-byline.;
• Is Part Of: Circulation. Volume 146:Issue 18(2022)
• Page Start: 1344
• Page End: 1356
• Publication Date: 2022-08-29
• Subjects: anticoagulants -- clopidogrel -- COVID-19 -- hemorrhage -- platelet aggregation inhibitors -- thrombosis; Blood -- Circulation -- Periodicals; Cardiovascular system -- Periodicals; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; 616.1
• DOI: 10.1161/CIRCULATIONAHA.122.061533
• Languages: English
• ISSNs: 0009-7322

Abstract

Abstract : 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: https://www.clinicaltrials.gov ; Unique identifier: NCT04409834.