RCT 14,892 very late stage (9 days from symptom onset) hospitalized patients, not showing a significant difference in mortality with treatment. A statistically significant increased chance of hospital discharge was found for treatment <= 7 days from symptom onset (supplement page 52). Only 7% of patients were not receiving thromboprophylaxis. Authors note that the lack of benefit seen may be because there was no significant additional benefit given the high rates of antithrombotic therapy with LMWH. Authors also note that potential benefit may depend on treatment delay, especially if thrombi had developed before admission. Lower RR is shown for patients not on LMWH (0.83), and patients treated <= 7 days from onset (0.93). Results restricted to earlier treatment times are not provided. Patients already receiving aspirin were excluded. NCT04381936
Horby et al., 6/8/2021, Randomized Controlled Trial, United Kingdom, Europe, preprint, 35 authors.
risk of death, 4.0% lower, RR 0.96, p = 0.35, treatment 1222 of 7351 (16.6%), control 1299 of 7541 (17.2%).
risk of death, 17.0% lower, RR 0.83, p = 0.11, treatment 129 of 466 (27.7%), control 169 of 513 (32.9%), no LMWH, supplement page 54.
risk of death, 7.0% lower, RR 0.93, p = 0.25, treatment 1222 of 7351 (16.6%), control 1299 of 7541 (17.2%), <=7 days from onset, supplement page 52.
risk of mechanical ventilation, 5.0% lower, RR 0.95, p = 0.32, treatment 772 of 6993 (11.0%), control 829 of 7169 (11.6%).
Effect extraction follows pre-specified rules
prioritizing more serious outcomes. For an individual study the most serious
outcome may have a smaller number of events and lower statistical signficance,
however this provides the strongest evidence for the most serious outcomes
when combining the results of many trials.