Anticoagulation and Antiplatelet Therapy for Prevention of Venous and Arterial Thrombotic Events in Critically Ill Patients With COVID-19: COVID-PACT
- PMID: 36036760
- PMCID: PMC9624238
- DOI: 10.1161/CIRCULATIONAHA.122.061533
Anticoagulation and Antiplatelet Therapy for Prevention of Venous and Arterial Thrombotic Events in Critically Ill Patients With COVID-19: COVID-PACT
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.
Keywords: COVID-19; anticoagulants; clopidogrel; hemorrhage; platelet aggregation inhibitors; thrombosis.
Figures
Similar articles
-
Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial.JAMA. 2021 Apr 27;325(16):1620-1630. doi: 10.1001/jama.2021.4152. JAMA. 2021. PMID: 33734299 Free PMC article. Clinical Trial.
-
Rivaroxaban for Prevention of Thrombotic Events, Hospitalization, and Death in Outpatients With COVID-19: A Randomized Clinical Trial.Circulation. 2023 Jun 20;147(25):1891-1901. doi: 10.1161/CIRCULATIONAHA.123.063901. Epub 2023 May 8. Circulation. 2023. PMID: 37154020 Free PMC article. Clinical Trial.
-
Aspirin Versus Clopidogrel for Long-Term Maintenance Monotherapy After Percutaneous Coronary Intervention: The HOST-EXAM Extended Study.Circulation. 2023 Jan 10;147(2):108-117. doi: 10.1161/CIRCULATIONAHA.122.062770. Epub 2022 Nov 7. Circulation. 2023. PMID: 36342475 Clinical Trial.
-
Efficacy and safety of heparin full-dose anticoagulation in hospitalized non-critically ill COVID-19 patients: a meta-analysis of multicenter randomized controlled trials.J Thromb Thrombolysis. 2022 Oct;54(3):420-430. doi: 10.1007/s11239-022-02681-x. Epub 2022 Aug 3. J Thromb Thrombolysis. 2022. PMID: 35922578 Free PMC article. Review.
-
Continuation versus discontinuation of antiplatelet therapy for bleeding and ischaemic events in adults undergoing non-cardiac surgery.Cochrane Database Syst Rev. 2018 Jul 18;7(7):CD012584. doi: 10.1002/14651858.CD012584.pub2. Cochrane Database Syst Rev. 2018. PMID: 30019463 Free PMC article. Review.
Cited by
-
Vascular Alterations Following COVID-19 Infection: A Comprehensive Literature Review.Life (Basel). 2024 Apr 24;14(5):545. doi: 10.3390/life14050545. Life (Basel). 2024. PMID: 38792566 Free PMC article. Review.
-
Predictors of bleeding and thrombotic events among patients admitted to the hospital with COVID-19 and elevated D-dimer: insights from the ACTION randomized clinical trial.J Thromb Thrombolysis. 2024 May 18. doi: 10.1007/s11239-024-02995-y. Online ahead of print. J Thromb Thrombolysis. 2024. PMID: 38762708
-
Effect of anticoagulation on the incidence of venous thromboembolism, major bleeding, and mortality among hospitalized COVID-19 patients: an updated meta-analysis.Front Cardiovasc Med. 2024 Apr 5;11:1381408. doi: 10.3389/fcvm.2024.1381408. eCollection 2024. Front Cardiovasc Med. 2024. PMID: 38646150 Free PMC article.
-
An early warning indicator of mortality risk in patients with COVID-19: the neutrophil extracellular traps/neutrophilic segmented granulocyte ratio.Front Immunol. 2024 Jan 29;15:1287132. doi: 10.3389/fimmu.2024.1287132. eCollection 2024. Front Immunol. 2024. PMID: 38348024 Free PMC article.
-
Effect of antiplatelet therapy after COVID-19 diagnosis: A systematic review with meta-analysis and trial sequential analysis.PLoS One. 2024 Feb 1;19(2):e0297628. doi: 10.1371/journal.pone.0297628. eCollection 2024. PLoS One. 2024. PMID: 38300975 Free PMC article.
References
-
- Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, Nigoghossian C, Ageno W, Madjid M, Guo Y, et al.. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020;75:2950–2973. doi: 10.1016/j.jacc.2020.04.031 - PMC - PubMed
Publication types
MeSH terms
Substances
Associated data
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous