Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy.
Venous thromboembolism (VTE) often complicates the clinical course of cancer. The risk is further increased by chemotherapy, but the trade-off between safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain. This is the third update of a review first published in February 2012.
To assess the efficacy and safety of primary thromboprophylaxis for VTE in ambulatory cancer patients receiving chemotherapy compared with placebo or no thromboprophylaxis, or an active control intervention.
For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 3 August 2020. We also searched the reference lists of identified studies and contacted content experts and trialists for relevant references.
Randomised controlled trials comparing any oral or parenteral anticoagulant or mechanical intervention to no thromboprophylaxis or placebo, or comparing two different anticoagulants.
We extracted data on risk of bias, participant characteristics, interventions, and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively. We applied GRADE to assess the certainty of evidence.
We identified six additional randomised controlled trials (3326 participants) for this update, bringing the included study total to 32 (15,678 participants), all evaluating pharmacological interventions and performed mainly in people with locally advanced or metastatic cancer. The certainty of the evidence ranged from high to very low across the different outcomes and comparisons. The main limiting factors were imprecision and risk of bias. Thromboprophylaxis with direct oral anticoagulants (direct factor Xa inhibitors apixaban and rivaroxaban) may decrease the incidence of symptomatic VTE (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.18 to 1.06; 3 studies, 1526 participants; low-certainty evidence); and probably increases the risk of major bleeding compared with placebo (RR 1.74, 95% CI 0.82 to 3.68; 3 studies, 1494 participants; moderate-certainty evidence). When compared with no thromboprophylaxis, low-molecular-weight heparin (LMWH) reduced the incidence of symptomatic VTE (RR 0.62, 95% CI 0.46 to 0.83; 11 studies, 3931 participants; high-certainty evidence); and probably increased the risk of major bleeding events (RR 1.63, 95% CI 1.12 to 2.35; 15 studies, 7282 participants; moderate-certainty evidence). In participants with multiple myeloma, LMWH resulted in lower symptomatic VTE compared with the vitamin K antagonist warfarin (RR 0.33, 95% CI 0.14 to 0.83; 1 study, 439 participants; high-certainty evidence), while LMWH probably lowers symptomatic VTE more than aspirin (RR 0.51, 95% CI 0.22 to 1.17; 2 studies, 781 participants; moderate-certainty evidence). 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. Only one study evaluated unfractionated heparin against no thromboprophylaxis, but did not report on VTE or major bleeding. When compared with placebo or no thromboprophylaxis, warfarin may importantly reduce symptomatic VTE (RR 0.15, 95% CI 0.02 to 1.20; 1 study, 311 participants; low-certainty evidence) and may result in a large increase in major bleeding (RR 3.82, 95% CI 0.97 to 15.04; 4 studies, 994 participants; low-certainty evidence). One study evaluated antithrombin versus no antithrombin in children. This study did not report on symptomatic VTE but did report any VTE (symptomatic and incidental VTE). The effect of antithrombin on any VTE and major bleeding is uncertain (any VTE: RR 0.84, 95% CI 0.41 to 1.73; major bleeding: RR 0.78, 95% CI 0.03 to 18.57; 1 study, 85 participants; very low-certainty evidence).
In ambulatory cancer patients, primary thromboprophylaxis with direct factor Xa inhibitors may reduce the incidence of symptomatic VTE (low-certainty evidence) and probably increases the risk of major bleeding (moderate-certainty evidence) when compared with placebo. LMWH decreases the incidence of symptomatic VTE (high-certainty evidence), but increases the risk of major bleeding (moderate-certainty evidence) when compared with placebo or no thromboprophylaxis. Evidence for the use of thromboprophylaxis with anticoagulants other than direct factor Xa inhibitors and LMWH is limited. More studies are warranted to evaluate the efficacy and safety of primary prophylaxis in specific types of chemotherapeutic agents and types of cancer, such as gastrointestinal or genitourinary cancer.
Rutjes AW
，Porreca E
，Candeloro M
，Valeriani E
，Di Nisio M
... -
《Cochrane Database of Systematic Reviews》
Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy.
Knee arthroscopy (KA) is a routine orthopedic procedure recommended to repair cruciate ligaments and meniscus injuries and in eligible patients, to assist the diagnosis of persistent knee pain. KA is associated with a small risk of thromboembolic events. This systematic review aims to assess if pharmacological or non-pharmacological interventions may reduce this risk. This review is the second update of the review first published in 2007.
To assess the efficacy and safety of interventions, whether mechanical, pharmacological, or in combination, for thromboprophylaxis in adult patients undergoing KA.
For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, the CENTRAL, MEDLINE, Embase and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries, on 14 August 2019.
We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs), whether blinded or not, of all types of interventions used to prevent deep vein thrombosis (DVT) in males and females aged 18 years and older undergoing KA. There were no restrictions on language or publication status.
Two authors independently selected studies for inclusion, assessed trial quality with the Cochrane 'Risk of bias' tool, and extracted data. A third author addressed discrepancies. We contacted study authors for additional information when required. We used GRADE to assess the certainty of the evidence.
This update adds four new studies, bringing the total of included studies to eight and involving 3818 adult participants with no history of thromboembolic disease undergoing KA. Studies compared daily subcutaneous (sc) low-molecular-weight heparin (LMWH) versus control (five studies); oral rivaroxaban 10 mg versus placebo (one study); daily sc LMWH versus graduated compression stockings (GCS) (one study); and aspirin versus control (one study). The incidence of pulmonary embolism (PE) in all trials combined was low, with seven cases in 3818 participants.There were no deaths in any of the intervention or control groups. LMWH versus control When compared with control, LMWH probably results in little to no difference in the incidence of PE in patients undergoing KA (risk ratio (RR) 1.81, 95% confidence interval (CI) 0.49 to 6.65; 1820 participants; 3 studies; moderate-certainty evidence). LMWH showed no reduction of the incidence of symptomatic DVT (RR 0.61, 95% CI 0.18 to 2.03; 1848 participants; 4 studies; moderate-certainty evidence). LMWH may reduce the risk of asymptomatic DVT but the evidence is very uncertain (RR 0.14, 95% CI 0.03 to 0.61; 369 participants; 2 studies; very low-certainty evidence). There was no evidence of an increased risk of all adverse events combined (RR 1.85, 95% CI 0.95 to 3.59; 1978 participants; 5 studies; moderate-certainty evidence). No evidence of a clear effect on major bleeding (RR 0.98, 95% CI 0.06 to 15.72; 1451 participants; 1 study; moderate-certainty evidence), or minor bleeding was observed (RR 1.79, 95% CI 0.84 to 3.84; 1978 participants; 5 studies; moderate-certainty evidence). Rivaroxaban versus placebo One study with 234 participants compared oral rivaroxaban 10 mg versus placebo. No evidence of a clear impact on the risk of PE (no events in either group), symptomatic DVT (RR 0.16, 95% CI 0.02 to 1.29; moderate-certainty evidence); or asymptomatic DVT (RR 0.95, 95% CI 0.06 to 15.01; very low-certainty evidence) was detected. Only bleeding adverse events were reported. No major bleeds occurred in either group and there was no evidence of differences in minor bleeding between the groups (RR 0.63, 95% CI 0.18 to 2.19; moderate-certainty evidence). Aspirin versus control One study compared aspirin with control. No PE, DVT or asymptomatic events were detected in either group. Adverse events including pain and swelling were reported but it was not clear what groups these were in. No bleeds were reported. LMWH versus GCS One study with 1317 participants compared the use of LMWH versus GCS. There was no clear difference in the risk of PE (RR 1.00, 95% CI 0.14 to 7.05; low-certainty evidence). LMWH use did reduce the risk of DVT compared to people using GCS (RR 0.17, 95% CI 0.04 to 0.75; low-certainty evidence). No clear difference in effects was seen between the groups for asymptomatic DVT (RR 0.47, 95% CI 0.21 to 1.09; very low-certainty evidence); major bleeding (RR 3.01, 95% CI 0.61 to 14.88; moderate-certainty evidence) or minor bleeding (RR 1.16, 95% CI 0.64 to 2.08; moderate-certainty evidence). Levels of thromboembolic events were higher in the GCS group than in any other group. We downgraded the certainty of the evidence for imprecision resulting from overall small event numbers; risk of bias due to concerns about lack of blinding, and indirectness as we were uncertain about the direct clinical relevance of asymptomatic DVT detection.
There is a small risk that healthy adult patients undergoing KA will develop venous thromboembolism (PE or DVT). There is moderate- to low-certainty evidence of no benefit from the use of LMWH, aspirin or rivaroxaban in reducing this small risk of PE or symptomatic DVT. There is very low-certainty evidence that LMWH use may reduce the risk of asymptomatic DVT when compared to no treatment but it is uncertain how this directly relates to incidence of DVT or PE in healthy patients. No evidence of differences in adverse events (including major and minor bleeding) was seen, but data relating to this were limited due to low numbers of events in the studies reporting within the comparisons.
Perrotta C
，Chahla J
，Badariotti G
，Ramos J
... -
《Cochrane Database of Systematic Reviews》
ResearchGate
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