Covid-19 living Data

Pharmacologic treatments for covid-19 patients

Therapeutic anticoagulant vs Prophylactic anticoagulant

This comparison will not be updated. Last search date 28 Feb, 2022.

Hospitalized patients

Forest plots
(last update: 2022-04-29)

Summary of findings
(last update: 2022-05-04)

Patient or population: COVID-19 patients
Setting: Worldwide
Intervention: Therapeutic anticoagulant
Comparison: Prophylactic anticoagulant

Outcome	Relative effect (95% CI)	Absolute effect (95% CI)¹		Certainty of the Evidence (GRADE)
Clinical improvement D28	RR: 1.00 (0.95 - 1.05)	0 fewer per 1000 (from 41 fewer to 41 more)		Low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level: some concerns or high risk regarding deviation from intended intervention, missing data, outcome measurement and selection of the reported results Inconsistency: Serious Inconsistency downgraded by 1 level: I²=:65.4% Indirectness: Not serious Imprecision: Not serious
6 trials Goligher E, 2021; Lawler PR, 2021, Lopes RD, 2021; Marcos M, 2021; Spyropouplos A, 2021; Sholzberg M, 2021 4853 participants		Therapeutic anticoagulant 816 per 1,000 (775 - 856)	Prophylactic anticoagulant 816 per 1,000
Clinical improvement D60	Outcome not yet measured or reported
WHO progression score (level 7 or above) D28	RR: 0.89 (0.67 - 1.18)	13 fewer per 1000 (from 40 fewer to 22 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
3 trials Lawler PR, 2021; Lopes RD, 2021; Sholzberg M, 2021 3324 participants		Therapeutic anticoagulant 108 per 1,000 (81 - 144)	Prophylactic anticoagulant 122 per 1,000
WHO progression score (level 7 or above) D60	Outcome not yet measured or reported
All-cause mortality D28	RR: 0.75 (0.49 - 1.17)	53 fewer per 1000 (from 109 fewer to 36 more)		Very low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level: some concerns or high risk regarding adequate randomization, deviation from intended intervention, missing data and selection of the reported results Inconsistency: Serious Inconsistency downgraded by 1 level: I²=: 69.6% Indirectness: Not serious Imprecision: Very serious Imprecision downgraded by 2 levels: due to wide confidence interval consistent with the possibility for benefit and the possibility for harm and low number of participants
8 trials Marcos M, 2021; Sholzberg M, 2021; Lopes RD, 2021; Spyropoulos A, 2021; Rashidi F, 2021; Goligher E, 2021; Oliynyk O, 2021; Lemos ACB, 2020; 2723 participants		Therapeutic anticoagulant 160 per 1,000 (105 - 250)	Prophylactic anticoagulant 214 per 1,000	1 additional study was identified that assessed this outcome, but no results were reported.
All-cause mortality D60	RR: 0.89 (0.66 - 1.18)	9 fewer per 1000 (from 28 fewer to 15 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Multicentre study conducted across several countries, therefore not downgraded for indirectness Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
1 trials Lawler PR 2021 2244 participants		Therapeutic anticoagulant 73 per 1,000 (54 - 96)	Prophylactic anticoagulant 82 per 1,000	1 additional study was identified that assessed this outcome, but no results were reported.
Viral negative conversion D7	RR: 1.11 (0.73 - 1.69)	66 more per 1000 (from 162 fewer to 414 more)		Very low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level: some concerns or high risk regarding deviation from intended intervention, missing data, and selection of the reported results Inconsistency: Not serious Indirectness: Serious despite a multicentre design this is a single study from a single country, therefore results in this population might not be generalizable to other settings. Imprecision: Very serious due to wide confidence interval consistent with the possibility for benefit and the possibility for harm and very low number of participants
1 trials Marcos M, 2021 52 participants		Therapeutic anticoagulant 666 per 1,000 (438 - 1000)	Prophylactic anticoagulant 600 per 1,000
Adverse events	RR: 1.84 (0.27 - 12.56)	244 more per 1000 (from 212 fewer to 1000 more)		Very low certainty Reasons to downgrade Risk of bias: Not serious Despite some concerns with adequate randomization, deviation from intended intervention, outcome measurement and selection of the reported results, not downgraded for risk of bias because the studies with these concerns contributed only a small proportion of weight to the effect estimate Inconsistency: Serious Inconsistency downgraded by 1 level: I²=:54.6% Indirectness: Not serious We presume that the adverse event rates and the corresponding relative risks, are similar across diverse settings, therefore not downgraded for indirectness Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
2 trials Oliynyk O, 2021; Sholzberg M, 2021 549 participants		Therapeutic anticoagulant 534 per 1,000 (78 - 1000)	Prophylactic anticoagulant 290 per 1,000
Serious adverse events	RR: 1.41 (0.32 - 6.16)	52 more per 1000 (from 85 fewer to 648 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Despite some concerns or high risk regarding adequate randomization, deviation from intended intervention, missing data, outcome measurement and selection of the reported results not downgraded for risk of bias because the studies with these concerns contributed only a small proportion of weight to the effect estimate Inconsistency: Not serious Indirectness: Not serious Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
4 trials Marcos M, 2021; Spyropoulos A, 2021; Sholzberg M, 2021; Oliynyk O, 2021 806 participants		Therapeutic anticoagulant 177 per 1,000 (40 - 774)	Prophylactic anticoagulant 126 per 1,000

¹The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

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Permanent URL for this comparison: https://covid-nma.com/living_data/index.php?comparison=97

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Trial	Funding	Comparisons		Design	Participants	Sample size	Overall risk of bias Highest assessment	Full description
		Treatment 1	Treatment 2
N/A Rashidi F, Thromb Res, 2021 Full text Commentary	Not reported/unclear	Tissue-plasminogen activator Tissue-plasminogen activator Therapeutic anticoagulant	Therapeutic anticoagulant Prophylactic anticoagulant Prophylactic anticoagulant	RCT	Patients with confirmed COVID-19 (severe-critical) admitted to 2 centers in Iran.	N=15	Some concerns Details	Full description
0112U001413 (Ukraine) Oliynyk O, Life, 2021 Full text Commentary	Public/non profit	Therapeutic LMWH	Prophylactic anticoagulant	RCT	Patients with confirmed COVID-19 (critical) admitted to a single center in the Ukraine	N=126	Some concerns Details	Full description
NCT04604327 Marcos M, Thromb Haemost, 2021 Full text Commentary Commentary	Mixed	Therapeutic anticoagulant	Prophylactic anticoagulant	RCT	Patients with suspected or confirmed COVID-19 (mild-moderate) admitted to 5 centers in Spain.	N=65	High Details	Full description
NCT04401293 Spyropoulos A, JAMA Intern Med, 2021 Full text Commentary Commentary	Public/non profit	Therapeutic anticoagulant	Intermediate-Dose prophylactic anticoagulation	RCT	Patients with confirmed COVID-19 (moderate-critical) admitted to 12 centers in the USA	N=257	Some concerns Details	Full description
NCT04362085; NCT04444700 RAPID Sholzberg M, BMJ, 2021 Full text Full text Commentary Commentary Commentary	Public/non profit	Therapeutic Heparin	Prophylactic Heparin	RCT	Patients with confirmed COVID-19 (moderate-severe) admitted to a 28 centers in Brazil, Canada, Ireland, Saudi Arabia, UAE, USA.	N=465	Some concerns Details	Full description
NCT04394377 ACTION Lopes RD, Lancet , 2021 Full text 01203-4/fulltext Commentary Commentary (21)01291-5/fulltext	Mixed	Therapeutic anticoagulant	Prophylactic anticoagulant	RCT	Patients with confirmed COVID-19 (mild-critical) admitted to 31 centers in Brazil	N=615	Some concerns Details	Full description
NCT02735707, NCT04505774, NCT04359277, NCT04372589 Lawler PR, N Engl J Med, 2021 Full text Full text Commentary	Mixed	Therapeutic Heparin	Prophylactic anticoagulant	RCT	Patients with confirmed COVID-19 (mild-severe) admitted to 121 centers in Australia, Brazil, Canada, Mexico, Nepal, Netherlands, Spain, UK, USA.	N=2244	Some concerns Details	Full description
NCT02735707, NCT04505774, NCT04359277, NCT04372589 Goligher E, N Engl J Med, 2021 Full text Full text Commentary	Mixed	Therapeutic heparin	Prophylactic anticoagulant	RCT	Patients with confirmed COVID-19 (severe-critical) admitted to 393 centers in Australia, Brazil, Canada, Ireland, Mexico, Netherlands, New Zealand, Saudi Arabia, UK, USA	N=1207	Some concerns Details	Full description
RBR-949z6v Lemos ACB, Thromb Res, 2020 Full text Commentary	No specific funding	Therapeutic enoxaparin	Prophylactic anticoagulant	RCT	Patients with confirmed COVID-19 (critical) admitted to a single center in Brazil	N=20	Some concerns Details	Full description