Summary of findings 1. Higher‐dose anticoagulants compared to lower‐dose anticoagulants for people hospitalised with COVID‐19.
| Higher‐dose anticoagulants compared to lower‐dose anticoagulants for people hospitalised with COVID‐19 | ||||||
| Patient or population: people hospitalised with COVID‐19 Setting: hospital Intervention: higher‐dose anticoagulants (LMWH, UFH or rivaroxaban) Comparison: lower‐dose anticoagulants (LMWH or UFH) | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with lower‐dose anticoagulants (short‐term outcomes) | Risk with higher‐dose anticoagulants | |||||
|
All‐cause mortality Follow‐up: from 28‐30 days |
Study population | RR 1.03 (0.92 to 1.16) | 4489 (4 RCTs) | ⊕⊕⊕⊕ Higha | Higher‐dose anticoagulants results in little to no difference in all‐cause mortality | |
| 191 per 1000 | 196 per 1000 (175 to 221) | |||||
|
Necessity for additional respiratory support Follow‐up: from 28‐30 days |
Study population | RR 0.54 (0.12 to 2.47) | 3407 (3 RCTs) | ⊕⊝⊝⊝ Very lowb,c,d | The evidence is very uncertain about the effect of higher‐dose anticoagulants on necessity for additional respiratory support. | |
| 117 per 1000 | 63 per 1000 (14 to 289) | |||||
| Mortality related to COVID‐19 | No studies measured this outcome | |||||
|
Deep vein thrombosis Follow‐up: from 28‐30 days |
Study population | RR 1.08 (0.57 to 2.03) | 3422 (4 RCTs) | ⊕⊕⊝⊝ Lowd | Higher‐dose anticoagulants may result in little to no difference in DVT | |
| 11 per 1000 | 12 per 1000 (6 to 22) | |||||
|
Pulmonary embolism Follow‐up: from 28‐30 days |
Study population | RR 0.46 (0.31 to 0.70) | 4360 (4 RCTs) | ⊕⊕⊕⊝ Moderateb | Higher‐dose anticoagulants likely reduce PE | |
| 33 per 1000 | 15 per 1000 (10 to 23) | |||||
|
Major bleeding Follow‐up: from 28‐30 days |
Study population | RR 1.78 (1.13 to 2.80) | 4400 (4 RCTs) | ⊕⊕⊕⊝ Moderateb | Higher‐dose anticoagulants likely increase major bleeding slightly | |
| 14 per 1000 | 24 per 1000 (15 to 38) | |||||
|
Adverse events (minor bleeding) Follow‐up: from 28‐30 days |
Study population | RR
3.28 (1.75 to 6.14) |
1196 (3 RCTs) | ⊕⊕⊕⊕ High | Higher‐dose anticoagulants increase adverse events (minor bleeding) | |
| 20 per 1000 | 47 per 1000 (18 to 121) | |||||
| *The 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; COVID‐19: coronavirus disease 2019; DVT: deep vein thrombosis; LMWH: low‐molecular‐weight heparin; PE: pulmonary embolism; RCT: randomised controlled trial; RR: risk ratio; UFH: unfractionated heparin | ||||||
| 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. | ||||||
aThe largest study in the analysis was at high risk of bias in almost all domains; however, we did not downgrade for study limitations as removing this study in the sensitivity analysis did not change the pooled estimate. bDowngraded one level due to study limitations. One randomised controlled trial provided high risk of bias in almost all domains leading to a different pooled estimate after sensitivity analysis. cDowngraded one level due to inconsistency. We identified substantial unexplained heterogeneity (I² = 60%). dDowngraded two levels due to imprecision. Confidence interval of the absolute difference comprises both important clinical benefit and important clinical harm.