Therapeutic-dose anticoagulation or thromboprophylaxis with low-molecular-weight heparin for moderate Covid-19: meta-analysis of randomized controlled trials

Ena, Javier; Valls, Victoria

doi:10.1007/s10238-022-00876-3

Cited by 3 publications

(9 citation statements)

References 33 publications

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“…Our results suggest that (1) HD-PA use, given its 4-fold reduction thrombosis risk compared with SD-PA use, is the lowest effective dose to prevent de novo macrovascular thrombosis, and (2) TA use does not outperform HD-PA use in lowering thrombotic risk. Our results concur with those of a multiplatform trial and the COVID-PACT trial of critically ill patients, and with the meta-analysis of Ena and Valls that showed that TA reduced macrovascular thrombosis. Of note, 4 of 5 RCTs included in the meta-analysis enrolled patients with high D-dimer levels .…”

Section: Discussionsupporting

confidence: 90%

“…No absolute value reported for the primary end point effect estimate, ie, probability of more favorable outcome because the probability for either group is itself the comparator effect estimate; their combined probability equals 100%. c Median (IQR) time to first thrombosis event was 6 (4-13) days in the SD-PA, 12 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) CTPA was similar in the 3 groups. Second, a relatively small number of patients were randomized, based on assumptions and power calculations for the primary hierarchical outcome.…”

Section: Efficacy and Safety Outcomesmentioning

confidence: 97%

“…No absolute value reported for the primary end point effect estimate, ie, probability of more favorable outcome because the probability for either group is itself the comparator effect estimate; their combined probability equals 100%. c Median (IQR) time to first thrombosis event was 6 (4-13) days in the SD-PA, 12 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) days in the HD-PA group, and 11 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) days in the TA group (P = .33).…”

Section: Efficacy and Safety Outcomesmentioning

confidence: 99%

“…Meta-analyses of randomized clinical trials (RCTs) of noncritically ill and critically ill patients reported that TA significantly reduced venous thromboembolic risk, with no significant effect on death or organ support. In contrast, escalating heparin dose with HD-PA showed no benefit to thrombosis or mortality in an RCT of noncritically ill patients and 2 RCTs of critically ill patients .…”

Section: Introductionmentioning

confidence: 99%

“…1,2 Given that observational data show macrovascular thrombosis in 10% to 30% of patients with COVID-19 receiving standard-dose prophylactic anticoagulation (SD-PA), [2][3][4] several institutions have recommended the use of high-dose prophylactic anticoagulation (HD-PA) and therapeutic anticoagulation (TA), either empirically or according to certain criteria, such as body mass index (BMI) or D-dimer concentration. [5][6][7] Meta-analyses of randomized clinical trials (RCTs) of noncritically ill 8 and critically ill patients 9 reported that TA significantly reduced venous thromboembolic risk, with no significant effect on death or organ support. In contrast, escalating heparin dose with HD-PA showed no benefit to thrombosis or mortality in an RCT of noncritically ill patients 10 and 2 RCTs of critically ill patients.…”

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confidence: 99%

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Effects of Standard-Dose Prophylactic, High-Dose Prophylactic, and Therapeutic Anticoagulation in Patients With Hypoxemic COVID-19 Pneumonia

et al. 2023

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ImportanceGiven the high risk of thrombosis and anticoagulation-related bleeding in patients with hypoxemic COVID-19 pneumonia, identifying the lowest effective dose of anticoagulation therapy for these patients is imperative.ObjectivesTo determine whether therapeutic anticoagulation (TA) or high-dose prophylactic anticoagulation (HD-PA) decreases mortality and/or disease duration compared with standard-dose prophylactic anticoagulation (SD-PA), and whether TA outperforms HD-PA; and to compare the net clinical outcomes among the 3 strategies.Design, Settings, and ParticipantsThe ANTICOVID randomized clinical open-label trial included patients with hypoxemic COVID-19 pneumonia requiring supplemental oxygen and having no initial thrombosis on chest computer tomography with pulmonary angiogram at 23 health centers in France from April 14 to December 13, 2021. Of 339 patients randomized, 334 were included in the primary analysis—114 patients in the SD-PA group, 110 in the HD-PA, and 110 in the TA. At randomization, 90% of the patients were in the intensive care unit. Data analyses were performed from April 13, 2022, to January 3, 2023.InterventionsPatients were randomly assigned (1:1:1) to receive either SD-PA, HD-PA, or TA with low-molecular-weight or unfractionated heparin for 14 days.Main Outcomes and MeasuresA hierarchical criterion of all-cause mortality followed by time to clinical improvement at day 28. Main secondary outcome was net clinical outcome at day 28 (composite of thrombosis, major bleeding, and all-cause death).ResultsAmong the study population of 334 individuals (mean [SD] age, 58.3 [13.0] years; 226 [67.7%] men and 108 [32.3%] women), use of HD-PA and SD-PA had similar probabilities of favorable outcome (47.3% [95% CI, 39.9% to 54.8%] vs 52.7% [95% CI, 45.2% to 60.1%]; P = .48), as did TA compared with SD-PA (50.9% [95% CI, 43.4% to 58.3%] vs 49.1% [95% CI, 41.7% to 56.6%]; P = .82) and TA compared with HD-PA (53.5% [95% CI 45.8% to 60.9%] vs 46.5% [95% CI, 39.1% to 54.2%]; P = .37). Net clinical outcome was met in 29.8% of patients receiving SD-PA (20.2% thrombosis, 2.6% bleeding, 14.0% death), 16.4% receiving HD-PA (5.5% thrombosis, 3.6% bleeding, 11.8% death), and 20.0% receiving TA (5.5% thrombosis, 3.6% bleeding, 12.7% death). Moreover, HD-PA and TA use significantly reduced thrombosis compared with SD-PA (absolute difference, −14.7 [95% CI −6.2 to −23.2] and −14.7 [95% CI −6.2 to −23.2], respectively). Use of HD-PA significantly reduced net clinical outcome compared with SD-PA (absolute difference, −13.5; 95% CI −2.6 to −24.3).Conclusions and RelevanceThis randomized clinical trial found that compared with SD-PA, neither HD-PA nor TA use improved the primary hierarchical outcome of all-cause mortality or time to clinical improvement in patients with hypoxemic COVID-19 pneumonia; however, HD-PA resulted in significantly better net clinical outcome by decreasing the risk of de novo thrombosis.Trial RegistrationClinicalTrials.gov Identifier: NCT04808882

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Section: Discussionsupporting

confidence: 90%

Section: Efficacy and Safety Outcomesmentioning

confidence: 97%

“…No absolute value reported for the primary end point effect estimate, ie, probability of more favorable outcome because the probability for either group is itself the comparator effect estimate; their combined probability equals 100%. c Median (IQR) time to first thrombosis event was 6 (4-13) days in the SD-PA, 12 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) days in the HD-PA group, and 11 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) days in the TA group (P = .33).…”

Section: Efficacy and Safety Outcomesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of Standard-Dose Prophylactic, High-Dose Prophylactic, and Therapeutic Anticoagulation in Patients With Hypoxemic COVID-19 Pneumonia

et al. 2023

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Thromboprophylaxis in Pregnant Women with COVID-19: An Unsolved Issue

Varlas

Borş

Plotogea

et al. 2023

IJERPH

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SARS-CoV-2 infection in pregnant women is of growing interest due to controversy over the use of antiplatelet and/or anticoagulant drugs during pregnancy and postpartum. Pregnant women are susceptible to develop severe forms of viral infections due to pregnancy-related immune alterations, changes in lung functions, and hypercoagulability. The association of pregnancy with SARS-CoV-2 infection can cause an increased incidence of thrombotic complications, especially in the case of patients with some genetic variants that favor inflammation and thrombosis. Compared to the general population, pregnant women may be at increased risk of thrombotic complications related to COVID-19. The lack of extensive clinical trials on thromboprophylaxis and extrapolating data from non-pregnant patients lead to major discrepancies in treating pregnant women with COVID-19. Currently, a multidisciplinary team should determine the dose and duration of prophylactic anticoagulant therapy for these patients, depending on the disease severity, the course of pregnancy, and the estimated due date. This narrative review aims to evaluate the protective effect of thromboprophylaxis in pregnant women with COVID-19. It is unknown at this time whether antiplatelet or anticoagulant therapy initiated at the beginning of pregnancy for various diseases (preeclampsia, intrauterine growth restriction, thrombophilia) offers a degree of protection. The optimal scheme for thromboprophylaxis in pregnant women with COVID-19 must be carefully established through an individualized decision concerning gestational age and the severity of the infection.

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Major Bleeding Events in Hospitalized COVID-19 Patients: A Retrospective Observational Study

Poloni,

Casalini,

Pozza

et al. 2024

Medicina

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Thromboprophylaxis/anticoagulation treatment is often required in hospitalized COVID-19 patients. We aimed to estimate the prevalence of major bleeding events in hospitalized COVID-19 patients. This was a retrospective observational study including all COVID-19 hospitalized patients ≥18 years of age at one reference center in northern Italy. The crude prevalence (between February 2020–2022) of major bleeding events was estimated as the number of major bleeding episodes divided by patients at risk. Uni- and multivariable Cox models were built to assess factors potentially associated with major bleeding events. Twenty-nine (0.98%) out of 2,945 COVID-19 patients experienced a major bleeding event [prevalence of 0.55% (95%CI 0.37–0.79)], of which five were fatal. Patients who experienced a major bleeding event were older [78 years (72–84 IQR) vs. 67 years (55–78 IQR), p-value < 0.001] and more frequently exposed to anti-aggregating therapy (44.8% vs. 20.0%, p-value 0.002) when compared to those who did not. In the multivariable Cox model, age [per 1 year more AHR 1.05 (CI95% 1.02–1.09)] was independently associated with an increased risk of major bleeding events. A strict monitoring of older hospitalized COVID-19 patients is warranted due to the risk of major bleeding events.

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Therapeutic-dose anticoagulation or thromboprophylaxis with low-molecular-weight heparin for moderate Covid-19: meta-analysis of randomized controlled trials

Cited by 3 publications

References 33 publications

Effects of Standard-Dose Prophylactic, High-Dose Prophylactic, and Therapeutic Anticoagulation in Patients With Hypoxemic COVID-19 Pneumonia

Effects of Standard-Dose Prophylactic, High-Dose Prophylactic, and Therapeutic Anticoagulation in Patients With Hypoxemic COVID-19 Pneumonia

Thromboprophylaxis in Pregnant Women with COVID-19: An Unsolved Issue

Major Bleeding Events in Hospitalized COVID-19 Patients: A Retrospective Observational Study

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