Routine primary prophylaxis for venous thromboembolism (VTE) cannot be suggested for all cancer patients receiving chemotherapy.
The recommendation is weak because of conflicting trials, potential bleeding, the need for laboratory monitoring and dose adjustment, and the relatively low incidence of VTE.
A Cochrane review [Abstract] 1 included 32 studies with a total of 15 678 subjects to assess the efficacy and safety of primary thromboprophylaxis in ambulatory cancer patients receiving chemotherapy. All studies evaluated pharmacological interventions and performed mainly in people with locally advanced or metastatic cancer. The treatments evaluated consisted of LMWH (21 studies), the uLMWH semuloparin (1 study), UFH (2 studies), the VKA warfarin (5 studies), antithrombin (2 studies), and the oral direct factor Xa inhibitor apixaban (2 studies) and rivaroxaban (2 studies).
Thromboprophylaxis with direct oral anticoagulants (direct factor Xa inhibitors apixaban and rivaroxaban) tended to decrease the incidence of symptomatic VTE (RR 0.43, 95% CI 0.18 to 1.06; 3 studies, n=1 526) and increase the risk of major bleeding (RR 1.74, 95% CI 0.82 to 3.68; 3 studies, n=1 494) compared with placebo, although the differences were not statistically significant.
Low-molecular-weightheparin (LMWH) compared with placebo or no LMWH reduced the incidence of symptomatic VTE and increased the risk of major bleeding events (table T1). In participants with multiple myeloma, LMWH resulted in lower symptomatic VTE compared with warfarin (RR 0.33, 95% CI 0.14 to 0.83; 1 study, n=439) while LMWH seemed to lower symptomatic VTE more than aspirin (RR 0.51, 95% CI 0.22 to 1.17; 2 studies, n=781), but the difference was not statistically significant. Major bleeding was observed in none of the participants with multiple myeloma treated with LMWH or warfarin and in less than 1% of those treated with aspirin.
Warfarin seemed to reduce symptomatic VTE (RR 0.15, 95% CI 0.02 to 1.20; 1 study, n=311) and to result in a large increase in major bleeding (RR 3.82, 95% CI 0.97 to 15.04; 4 studies, n=994) compared with placebo or no thromboprophylaxis, although the observed differences were not statistically significant.
| Outcome | Number of participants (studies) | Asssumed risk - Placebo or no LMWH | Corresponding risk - LMWH (95% CI) | Relative effect (95% CI) |
|---|---|---|---|---|
| Symptomatic VTE | 3 931 (11) | 71 per 1000 | 44 per 1000(33 to 59) | RR 0.62 (0.46 to 0.83) |
| Major bleeding | 7 282 (15) | 11 per 1000 | 18 per 1000(12 to 26) | RR 1.63 (1.12 to 2.35) |
| Symptomatic PE | 5 324 (8) | 18 per 1000 | 11 per 1000(8 to 16) | RR 0.60 (0.42 to 0.88) |
| 1-year mortality | 2 681 (9) | 586 per 1000 | 551 per 1000(486 to 627) | RR 0.94 (0.83 to 1.07) |
Prophylaxis is suggested for hospitalized patients and patients with additional risk factors for VTE (patient, cancer or treatment-related) in absence of contraindications.
Marketing applications for the ultra-low molecular weight heparin semuloparin have been withdrawn worldwide, and it is therefore unlikely to ever be commercially available.
Date of latest search:
Primary/Secondary Keywords