Table 2.
Randomised clinical trials assessing pharmacological prophylaxis of venous thromboembolism in hospitalised acutely medically ill patients
| RCT | n | Cancer patients (n, %) | Study drug/schedule | All patients | Cancer subgroup | ||
|---|---|---|---|---|---|---|---|
| VTE events | MB | VTE events | CRB or MB | ||||
|
ARTEMIS [Cohen AT, BMJ. 2006] |
849 | HC: 131 (15.4%) |
Fondaparinux sc (2.5 mg/24 h) for 6–14 days vs Placebo No extended prophylaxis |
5.6 vs 10.5% RR: 0.47 p = 0.029 |
0.2 vs 0.2% p = NS |
17.0 vs 3.9% RR: 4.3 |
NR |
|
MEDENOX [Samama MM, N Engl J Med. 1999] |
738 | HC: 101 (13.7%) |
Enoxaparin sc (40 mg/24 h) for 6–14 days vs Placebo No extended prophylaxis |
5.5 vs 14.9% RR: 0.37 p < 0.001 |
1.7 vs 1.1% p = NS |
9.7 vs 19.5%, RR: 0.50 |
NR |
|
PREVENT [Leizorovicz A, Circulation. 2004] |
3706 | HC: 190 (5.1%) |
Dalteparin sc (5000 UI/24 h) for 14 days vs Placebo No extended prophylaxis |
2.8 vs 5.0% RR: 0.55 p = 0.0015 |
0.5 vs 0.2% p = NS |
3.1 vs 8.3% RR: 0.37 |
NR |
|
EXCLAIM [Hull RD, Ann Intern Med. 2010] |
5963 |
HC: 818 (13.7%) AC: 100 (1.7%) (*) |
Enoxaparin sc (40 mg/24 h) for 10 ± 4 days, then enoxaparin sc (40 mg/24 h) for additional 28 ± 4 days vs Enoxaparin sc (40 mg/24 h) for 10 ± 4 days Extended prophylaxis for enoxaparin |
2.5 vs 4.0% ARD: − 1.53% (95% CI − 2.54% to − 0.52%) |
0.8 vs 0.3% ARD: 0.51% (95% CI 0.12% to 0.89%) |
OR: 0.71 (95% CI 0.33–1.53) | NR |
|
ADOPT [Goldhaber SZ, N Engl J Med. 2011] |
6528 |
HC: 632 (9.7%) AC: 211 (3.2%) |
Oral apixaban (2.5 mg/12 h) for 30 days vs Enoxaparin sc (40 mg/24 h) for 6–14 days Extended prophylaxis for apixaban |
2.71 vs 3.06% RR: 0.87 p = 0.44 |
0.47 vs 0.19% RR: 2.58 p = 0.04 |
NR | NR |
|
MAGELLAN [Cohen AT, N Engl J Med. 2013] |
8101 |
HC: 1378 (17.0%) AC: 592 (7.3%) (*) |
Oral rivaroxaban (10 mg/24 h) for 35 ± 4 days vs Enoxaparin sc (40 mg/24 h) for 10 ± 4 days Extended prophylaxis for rivaroxaban |
4.4 vs 5.7% RR: 0.77 p = 0.02 |
4.1 vs 1.7% RR: 2.5 p < 0.001 |
6.9 vs 7.9% OR: 0.87 (95% CI 0.51–1.48) |
5.7 vs 1.8% OR: 3.2 (95% CI 1.6–6.5) |
|
APEX [Cohen AT, N Engl J Med. 2016] |
7513 |
HC: 909 (12.1%) AC: 37 (0.49%) (*) |
Oral betrixaban (80 mg/24 h) for 35–42 days vs Enoxaparin sc (40 mg/24 h) for 10 ± 4 days |
5.3 vs 7.0% RR: 0.76 p = 0.006 |
0.7 vs 0.6% p = 0.55 |
5.7 vs 6.2% OR: 0.92 (95% CI 0.54–1.58) |
2.8 vs 1.9% OR: 1.44 (95% CI 0.62–3.36) |
|
MARINER [Spyropoulos AC; N Engl J Med. 2018] |
12,019 |
HC: 1022 (8.5%) AC: excluded (**) |
Oral rivaroxaban (10 mg/24 h) for 45 days vs Placebo for 45 days after discharge Extended prophylaxis for rivaroxaban |
0.83 vs 1.1% RR: 0.76 p = 0.14 |
0.28% vs 0.15% RR: 1.88 p = NS |
1.02 vs 1.31 OR: 0.78 (95% CI 0.25–2.47) |
3.7 vs 2.1% OR: 1.8 (95% CI 0.9–3.9) |
AC active cancer, ARD absolute risk difference, CI confidence interval, CRB clinically relevant bleeding, HC history of cancer (active and remote cancer), MB major bleeding, n sample size, NR not reported, NS not significant, OR odds ratio, p significance level, RCT randomised clinical trials, RR relative risk, sc subcutaneous, vs versus, VTE venous thromboembolism
(*) Excludes intracranial neoplasm or metastasis. (**) Excludes all active cancers