Primary Thromboprophylaxis in Ambulatory Cancer Patients: Where Do We Stand?

Mulder, Frits I.; Bosch, Floris T. M.; Es, Nick van

doi:10.3390/cancers12020367

Cited by 16 publications

(24 citation statements)

References 86 publications

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“…The optimal way of identifying ambulatory cancer patients at high risk of VTE remains a matter of debate. 2,6,17,40,50,51 In this metaanalysis, we focused on the Khorana score, because it is the most widely studied and used risk-stratification tool. However, a substantial variation in VTE risk has been observed across different tumor types within the same Khorana score risk group.…”

Section: Discussionmentioning

confidence: 99%

“…3 VTE can lead to interruption or postponement of cancer treatment, decreased quality of life, 4 morbidity, and death. 5,6 The goal of primary thromboprophylaxis is to reduce the risk of first-time VTE and, consequently, its short-and long-term sequelae. Several randomized trials have evaluated the efficacy and safety of prophylactic-dose low molecular weight heparin (LMWH) for VTE prevention in ambulatory cancer patients.…”

Section: Introductionmentioning

confidence: 99%

“…17 Because the incidence in patients at intermediate risk is lower than in patients at high VTE risk, the NNT will increase accordingly. 6,17 Although the 2 trials demonstrated the efficacy of prophylactic DOACs in all patients with an intermediate to high risk ($2 points), it remains unclear whether the effect of thromboprophylaxis is consistent in patients at intermediate risk compared with those at high risk, because these trials did not have enough statistical power for this subgroup analysis.…”

Section: Introductionmentioning

confidence: 99%

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Primary thromboprophylaxis in ambulatory cancer patients with a high Khorana score: a systematic review and meta-analysis

et al. 2020

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Guidelines suggest thromboprophylaxis for ambulatory cancer patients starting chemotherapy with an intermediate to high risk of venous thromboembolism (VTE) according to Khorana score. Data on thromboprophylaxis efficacy in different Khorana score risk groups remain ambiguous. We sought to evaluate thromboprophylaxis in patients with an intermediate- to high-risk (≥2 points) Khorana score and an intermediate-risk score (2 points) or high-risk score (≥3 points) separately. MEDLINE, Embase, and CENTRAL were searched for randomized controlled trials (RCTs) comparing thromboprophylaxis with placebo or standard care in ambulatory cancer patients. Outcomes were VTE, major bleeding, and all-cause mortality. Relative risks (RRs) were calculated in a profile-likelihood random-effects model. Six RCTs were identified, involving 4626 cancer patients. Thromboprophylaxis with direct oral anticoagulants (DOACs) or low molecular weight heparin (LMWH) significantly reduced VTE risk in intermediate- to high-risk (RR, 0.51; 95% confidence interval [CI], 0.34-0.67), intermediate-risk (RR, 0.58; 95% CI, 0.36-0.83), and high-risk patients (RR, 0.45; 95% CI, 0.28-0.67); the numbers needed to treat (NNTs) were 25 (intermediate to high risk), 34 (intermediate risk), and 17 (high risk), respectively. There was no significant difference in major bleeding (RR, 1.06; 95% CI, 0.69-1.67) or all-cause mortality (RR, 0.90; 95% CI, 0.82-1.01). The numbers needed to harm (NNHs) for major bleeding in intermediate- to high-risk, intermediate-risk, and high-risk patients were 1000, −500, and 334, respectively. The overall NNH was lower in DOAC studies (100) versus LMWH studies (−500). These findings indicate thromboprophylaxis effectively reduces the risk of VTE in patients with an intermediate- to high-risk Khorana score, although the NNT is twice as high for intermediate-risk patients compared with high-risk patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Primary thromboprophylaxis in ambulatory cancer patients with a high Khorana score: a systematic review and meta-analysis

et al. 2020

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“…Other authors have tried to improve the Khorana score performance and proposed modifications by adding biomarkers, types of chemotherapy or performance status [52,66,67]. A recently published review aimed at the optimization of thromboprophylaxis in cancer patients has been considering all these aspects and suggested that prediction scores might be developed for specific cancer sites [68]. Pabinger et al [69] developed and validated a nomogram that included only tumor site risk category and D-dimer to assess the risk of VTE in chemotherapy-treated cancer patients [69].…”

Section: Vte Prophylaxismentioning

confidence: 99%

“…Proposed algorithm for a therapeutic strategy based on the evaluation of venous thromboembolism (VTE) risk in patients with advanced cancer on a simultaneous care program. The classical category of the Intermediate-risk patients defined by the Khorana score is no longer included, since the integration of detailed programs and evaluations allows a more specific discrimination among patients[68][69][70]73]. CHT: Chemotherapy; ECOG-PS: ECOG-Performance Status; TPX: Thromboprophylaxis.…”

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confidence: 99%

Venous Thromboembolism in Cancer Patients on Simultaneous and Palliative Care

Riondino

Ferroni

Monte

et al. 2020

Cancers

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Simultaneous care represents the ideal integration between early supportive and palliative care in cancer patients under active antineoplastic treatment. Cancer patients require a composite clinical, social and psychological management that can be effective only if care continuity from hospital to home is guaranteed and if such a care takes place early in the course of the disease, combining standard oncology care and palliative care. In these settings, venous thromboembolism (VTE) represents a difficult medical challenge, for the requirement of acute treatments and for the strong impact on anticancer therapies that might be delayed or, even, totally discontinued. Moreover, cancer patients not only display high rates of VTE occurrence/recurrence but are also more prone to bleeding and this forces clinicians to optimize treatment strategies, balancing between hemorrhages and thrombus formation. VTE prevention is, therefore, regarded as a double-edged sword. Indeed, while on one hand the appropriate use of antithrombotic agents can reduce VTE occurrence, on the other it significantly increases the bleeding risk, especially in the frail patients who present with multiple co-morbidities and poly-therapy that can interact with anticoagulant drugs. For these reasons, thromboprophylaxis should start while active cancer treatment is ongoing, according to a simultaneous care model in a patient-centered perspective.

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D-Dimer Enhances Risk-Targeted Thromboprophylaxis in Ambulatory Patients with Cancer

et al. 2020

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Background. Thromboprophylaxis for ambulatory patients with cancer is effective, although uncertainties remain on who should be targeted. Using D-dimer values from individuals enrolled to the AVERT trial, we sought to identify and validate a more efficient venous thromboembolism (VTE) risk threshold for thromboprophylaxis. Materials and Methods. The AVERT trial compared thromboprophylaxis with apixaban with placebo among patients with cancer with a Khorana Risk Score ≥2. The D-dimer measured at randomization was used to calculate an individualized 6-month VTE risk using the validated CATScore. A modified intention-to-treat analysis was used to assess efficacy (VTE) and safety (major and overall bleeding) in the (a) complete cohort and (b) ≥8% and < 8% 6-month VTE risk thresholds. Results. Five hundred seventy-four patients were randomized in the AVERT trial; 466 (81%) with baseline D-dimer were included in the study. Two hundred thirty-seven subjects received apixaban; 229 received placebo. In the complete cohort, there were 13 (5.5%) VTE events in the apixaban arm compared with 26 (11.4%) events in the placebo arm (adjusted hazard ratio [aHR] 0.49 [0.25-0.95], p < .05). Number needed to treat (NNT) to prevent one VTE = 17. Eighty-two (35%) and 72 (31%) patients in the apixaban and placebo arms, respectively, had a 6-month VTE risk ≥8%. In this subgroup, 7 (8.4%) VTE events occurred with apixaban and 19 (26.3%) events with placebo (aHR 0.33 [0.14-0.81], p < .05), NNT = 6. Individuals with a VTE risk <8% derived no benefit from apixaban thromboprophylaxis (aHR 0.89 [0.30-2.65), p = .84). Increased rates of overall bleeding were observed with apixaban in both the complete (aHR 2.11 [1.09-4.09], p < .05) and ≥ 8% predicted risk cohorts (aHR 2.87 [0.91-9.13], p = .07). Conclusion. A 6-month VTE risk threshold of ≥8% increases the efficiency of risk-targeted thromboprophylaxis in ambulatory patients with cancer. The Oncologist 2020;25:1-9 Implications for Practice: Ambulatory patients with cancer receiving chemotherapy have an increased risk of venous thromboembolism (VTE). A Khorana Risk Score (KRS) ≥2 is currently the suggested threshold for thromboprophylaxis. Using baseline D-dimer values from individuals enrolled to the AVERT trial, this retrospective validation study identifies a 6-month VTE risk of ≥8% as a more efficient threshold for thromboprophylaxis. At this threshold, the number needed to treat to prevent one VTE is 6, compared with 17 when using a KRS ≥2. Conversely, individuals with a predicted risk of <8% derive no clinical benefit from thromboprophylaxis. Future prospective studies should validate this threshold for outpatient thromboprophylaxis.

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Primary Thromboprophylaxis in Ambulatory Cancer Patients: Where Do We Stand?

Cited by 16 publications

References 86 publications

Primary thromboprophylaxis in ambulatory cancer patients with a high Khorana score: a systematic review and meta-analysis

Primary thromboprophylaxis in ambulatory cancer patients with a high Khorana score: a systematic review and meta-analysis

Venous Thromboembolism in Cancer Patients on Simultaneous and Palliative Care

D-Dimer Enhances Risk-Targeted Thromboprophylaxis in Ambulatory Patients with Cancer

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