Maligniteit geassocieerde trombose

Publicatiedatum: 01-05-2026

Beoordeeld op geldigheid: 01-05-2026

Uitgangsvraag

Wat is het optimale antistollingsbeleid bij patiënten met een actieve maligniteit en een acute VTE, voor de initiële periode (eerste 3-6 maanden) en voor de langere termijn (na 6 maanden)?

Aanbeveling

Behandel patiënten met een maligniteit en een acute VTE met een therapeutische dosis DOAC (apixaban, edoxaban, rivaroxaban) of LMWH, volgens de doseringsvoorschriften vermeld in het Farmacotherapeutisch kompas.

Behandel patiënten met acute VTE en een niet-gereseceerde maligniteit van de tractus digestivus (inclusief lever-, galweg- en pancreastumoren) of tractus urogenitalis bij voorkeur met LMWH. Overweeg apixaban als alternatief.

Overweeg patiënten met een maligniteit en VTE met een indicatie voor langdurige behandeling met therapeutische antistolling, na de eerste zes maanden te behandelen met een gereduceerde dosis apixaban (2dd 2,5 mg), tenzij er contra-indicaties zijn voor een DOAC.

Overwegingen

Balans tussen gewenste en ongewenste effecten

Uit de analyse van de literatuur blijkt dat initiële behandeling met directe orale anticoagulantia (DOACs) bij patiënten met een acute maligniteit geassocieerde veneuze trombo-embolie (VTE) waarschijnlijk leidt tot een klinisch relevant lager risico op recidief VTE (cruciale uitkomst), vergeleken met een initiële behandeling met laag-moleculair-gewicht heparine (LMWH). Er is mogelijk geen klinisch relevant verschil in majeure bloedingen (cruciale uitkomst) tussen een behandeling met DOAC of een behandeling met LMWH. Voor mortaliteit (cruciale uitkomst) geldt dat er ook geen klinisch relevant verschil is tussen de twee behandelingen. Initiële behandeling met DOACs leidt waarschijnlijk tot een relevant hoger risico op klinisch relevante niet-majeure bloedingen (belangrijke uitkomst), vergeleken met een LMWH-behandeling. Voor de belangrijke uitkomst net clinical benefit geldt dat het bewijs te onzeker is om een uitspraak te kunnen doen over het effect van behandeling met DOACs vergeleken met LMWH gezien alleen 1 studie dit heeft onderzocht.

Hoewel in de meta-analyse het risico op majeure bloedingen niet klinisch relevant verschilde tussen behandeling met DOAC en LMWH bij acute maligniteit geassocieerde VTE , zijn er wel signalen uit de individuele studies dat sommige DOAC meer majeure bloedingen geven in specifieke situaties. Met name patiënten met een (in-situ) tumor in de tractus digestivus of tractus urogenitalis bleken in sommige studies vaker majeure bloedingen te krijgen. Om die reden werd bijvoorbeeld de eerste van die twee categorieën halverwege de SELECT-D studie niet meer geïncludeerd in de studie (Young, 2018). De vorige versie van de module gaf dan ook het advies patiënten met een maligniteit van de tractus digestivus (inclusief lever- en pancreastumoren) en de tractus urogenitalis bij voorkeur met LMWH te behandelen. De studies die in deze update van de module extra zijn meegenomen, met name de Caravaggio studie waarin apixaban is gebruikt en patiënten met gastro-intestinale en urogenitale maligniteiten wel zijn meegenomen, suggereerden een vergelijkbaar risico op majeure bloedingen bij behandeling met apixaban ten opzichte van LMWH. Hoewel de subgroep analyses te klein zijn om hier een harde uitspraak over te doen, beschouwt de richtlijncommissie apixaban als een redelijk alternatief voor LMWH in deze setting.

In de beschikbare studies over acute maligniteit geassocieerde VTE met DOAC en LMWH zijn sommige types patiënten (bijvoorbeeld met ernstige nierinsufficiëntie, trombocytopenie <100x10^9/l) of soorten maligniteiten (intracerebrale tumoren, hematologische maligniteiten zoals acute leukemie of na stamceltransplantatie) niet goed vertegenwoordigd. Het is niet duidelijk in hoeverre de gevonden resultaten en aanbevelingen daarom ook van toepassing zijn voor deze patiëntengroepen en type maligniteiten.

Interacties tussen DOACs en chemotherapeutica of andere comedicatie zijn maar in beperkte mate onderzocht. De opname en klaring van DOACs is afhankelijk van P-glycoproteïne en CYP450 enzymen, die allen kunnen worden geremd of versterkt door verschillende chemotherapeutica, immuuntherapie of andere medicatie zoals -azolen of anti-epileptica. Er zijn intrinsieke verschillen tussen de drie beschikbare DOACs, maar de klinische impact hiervan is niet bekend en niet vergeleken tussen de verschillende DOACs. De farmacologisch meest ‘optimale’ DOAC zou dus per patiënt, per soort maligniteit en per type chemotherapeuticum of co-medicatie kunnen verschillen. Het is van belang om samen met de patiënt af te wegen welke DOAC het meest passend is.

We hebben geen literatuur search gedaan naar de optimale duur van antistollingsbehandeling bij patiënten met een acute VTE en een actieve maligniteit. De beschreven adviezen zijn gebaseerd op de bestaande richtlijn Antitrombotisch beleid (2016), de ASH-guidelines voor behandeling van kanker-geassocieerde VTE (2021) en de behandelduur die is gehanteerd in de beoordeelde RCTs voor initiële behandeling van acute kanker-geassocieerde VTE. De duur van de antistollingsbehandeling bij patiënten met een acute VTE en een actieve maligniteit is tenminste zes maanden. Patiënten met een hoog bloedingsrisico dienen ten minste drie maanden behandeld te worden. Zolang er sprake is van actieve maligniteit dan wel chemotherapie of adjuvante behandeling kan worden overwogen om deze behandeling te verlengen.

Twee studies (EVE-trial en API-CAT-trial) hebben onderzocht of voor verlengde behandeling van kanker-geassocieerde VTE na zes maanden dosisreductie van apixaban (naar 2dd 2.5 mg) mogelijk is (McBane, 2025; Mahé, 2025). Deze studies lieten zien dat gereduceerde dosis apixaban non-inferieur was aan volledige dosering apixaban voor recidief VTE, maar wel resulteerde in een lager risico op de combinatie van ernstige en klinisch relevante niet-ernstige bloedingen. Derhalve kan, na een initiële behandeling met LMWH of DOAC van tenminste zes maanden, worden overwogen om over te gaan op gereduceerde dosis apixaban (2dd 2.5 mg). Voor de andere DOACs is dit niet onderzocht.

Bij voortgezette behandeling is het aan te bevelen regelmatig, en in ieder geval jaarlijks, een individuele afweging te maken tussen het verlagen van het recidief tromboserisico en het bloedingsrisico tijdens behandeling met antistolling.

Kwaliteit van bewijs

De overall kwaliteit van bewijs is laag. Dit betekent dat we onzeker zijn over het gevonden geschatte effect van de cruciale uitkomstmaten. Het is relevant om te benoemen dat de bewijskracht varieerde van laag (majeure bloeding) tot redelijk (recidief VTE) en hoog (mortaliteit).

Er is afgewaardeerd vanwege (zeer) ernstige:

Imprecisie: onnauwkeurigheid, omdat het betrouwbaarheidsinterval de grens/beide grenzen van klinische relevantie overschrijdt.

Waarden en voorkeuren van patiënten (en eventueel hun naasten/verzorgers)

De uitkomst van de kankerbehandeling (bijvoorbeeld progressievrije overleving en mortaliteit) en kwaliteit van leven zijn voor de meeste patiënten met kanker doorgaans het belangrijkst. De keus DOAC of LMWH lijkt geen invloed te hebben op overleving. Wel lijken DOACs geassocieerd met een lager risico op recidief trombo-embolie, maar met meer niet-majeure klinische relevante bloedingen, met grofweg dezelfde ‘number needed to treat/harm’. Hoewel maar 1 studie onderzoek heeft gedaan naar ‘net clinical benefit’, lijken de voordelen en nadelen van DOACs ten opzichte van LMWH tegen elkaar op te wegen voor behandeling van acute maligniteit geassocieerde VTE. Er is weinig onderzoek gedaan naar het effect van subcutane injecties versus orale medicatie op de kwaliteit van leven, maar de weinig beschikbare literatuur suggereert dat patiënten een voorkeur zullen hebben voor orale medicatie (Hutchinson, 2019). In de CANVAS-studie waren er geen relevante verschillen in patiënt-gerapporteerde kwaliteit van leven of beleving van de antistollingsbehandeling tussen patiënten behandeld met een DOAC of LMWH; wel was de therapie adherentie beter in patiënten die een DOAC kregen (Schrag, 2023).

Kostenaspecten

De interventie levert minder kosten op ten opzichte van de controle behandeling vanwege de lagere kosten van (generieke) DOACs ten opzichte van LMWH. Dit zou de keuze voor DOACs kunnen laten doorslaan in positieve wijze.

Gelijkheid ((health) equity/equitable)

De interventie leidt niet tot een toename van gezondheidsgelijkheid.

Aanvaardbaarheid

Ethische aanvaardbaarheid

Zowel DOACs als LMWH zijn aanvaardbaar voor alle betrokkenen.

Duurzaamheid

LMWH zijn minder duurzaam vanwege het restmateriaal (injectiespuit).

Haalbaarheid

Behandeling met zowel DOAC als LMWH is haalbaar. Het kunnen slikken van orale medicatie is een voorwaarde voor DOACs, terwijl het (zelfstandig) kunnen toedienen van subcutane injecties een voorwaarde is voor LMWH.

Rationale van de aanbeveling: weging van argumenten voor en tegen de interventies

Een behandeling met DOACs vs LMWH leidt niet tot een klinisch relevant verschil in mortaliteit. Daarnaast leidt een behandeling met een DOAC mogelijk tot minder recidief VTE, maar zonder verschil in majeure bloedingen t.o.v. behandeling met LMWH. Wel werden er meer klinisch relevante niet-majeure bloedingen gezien in de patiënten die een DOAC kregen. Om deze reden ziet de werkgroep ruimte om patiënten met een maligniteit geassocieerde acute VTE te behandelen met een DOAC of LMWH.

Eindoordeel:

Sterke aanbeveling voor Doen.

Onderbouwing

Achtergrond

In patients with cancer and acute venous thromboembolism (VTE), low-molecular-weight heparin (LMWH) at therapeutic doses was long considered the preferred treatment. This recommendation was based on several randomized trials comparing LMWH with vitamin K antagonists (VKAs), which demonstrated superior efficacy of LMWH in preventing recurrent VTE (Kahale, 2018). Over the past two decades, direct oral anticoagulants (DOACs) were introduced. Phase 3 trials comparing DOACs with VKAs in patients with acute VTE showed similar risks of recurrent VTE and bleeding, with a potential advantage of DOACs in reducing intracranial hemorrhage (van der Hulle, 2014; Posch, 2015; van Es, 2014). However, these studies included few patients with active cancer. Subsequently, several subsequent phase 3 trials have been conducted to evaluate the efficacy and safety of DOACs compared with LMWH specifically in patients with active cancer and acute VTE.

Conclusies / Summary of Findings

Summary of Findings

Initial anticoagulant treatment in patients with acute cancer-associated venous thromboembolism (VTE)

Population: Adults with active cancer and objectively confirmed acute deep vein thrombosis (DVT) and/or pulmonary embolism (PE)

Intervention: Direct oral anticoagulant (DOAC) – Rivaroxaban, edoxaban, apixaban

Comparator: Low-molecular-weight heparin (LMWH) – Dalteparin

Duration of treatment	Outcome	Study results and measurements	Absolute effect estimates		Certainty of the Evidence (Quality of evidence)	Conclusions
3-6 months			LMWH	DOAC
	Recurrent VTE (critical)	RR 0.66 (95%CI 0.50 to 0.87)	8 per 100	6 per 100	⨁⨁⨁◯ Moderate¹	Initial treatment with DOAC likely reduces the risk of a recurrent VTE when compared with LMWH in patients with acute cancer- associated VTE. .
	Major bleeding (critical)	RR 1.22 (95%CI 0.74 to 2.00)	4 per 100	5 per 100	⨁⨁◯◯ Low²	Initial treatment with DOAC may result in little to no difference in major bleeding events when compared with LMWH in patients with acute cancer-associated VTE.
	Mortality (critical)	RR 1.02 (95%CI 0.87 to 1.19)	29 per 100	29 per 100	⨁⨁⨁⨁ High	Initial treatment with DOAC results in little to no difference in mortality when compared with LMWH in patients with acute cancer-associated VTE.
	CRNMB (important)	RR 1.60 (95%CI 1.13 to 2.28)	7 per 100	12 per 100	⨁⨁⨁◯ Moderate¹	Initial treatment with DOAC likely increases the risk of a clinically relevant non-major bleeding when compared with LMWH in patients with acute cancer-associated VTE.
	Net clinical benefit (important)	HR 0.97 (95%CI 0.70 to 1.36)	14 per 100	13 per 100	⨁◯◯◯ Very low³	The evidence is very uncertain about the effect of initial treatment with DOAC on net clinical benefit when compared with LMWH in patients with acute cancer-associated VTE.
> 6 months			LMWH	DOAC
> 6 months	All outcomes	No trial could be included on the treatment duration longer than six months.

_{HR: hazard ratio; RR: risk ratio; CRNMB: clinically relevant non-major bleeding.}

_{¹ Downgraded because of imprecision (CI crosses one boundary of clinically important difference)}

_{² Downgraded because of imprecision (CI crosses both boundaries of clinically important difference)}

_{³ Downgraded because of risk of bias (industry sponsorship heavily involved in the trial) and imprecision (CI crosses both boundaries of clinically important difference)}

Samenvatting literatuur

Description of studies

A total of six studies were included in the analysis of the literature. Important study characteristics and results are summarized in Table 2. Of these studies, six investigated the initial treatment of cancer-associated VTE and none the long-term treatment of cancer-associated VTE (beyond the initial six months following diagnosis). In the trial of Raskob (2018), participants could continue the treatment beyond 6 months; however, this was up to the treating physician. The results on long-term treatment were therefore not included. The assessment of the risk of bias is summarized in the risk of bias tables (under the tab ‘Evidence tabellen’).

Young (2018) conducted the SELECT-D-trial, a multicenter, randomized, open label phase 3 pilot trial in the United Kingdom, comparing rivaroxaban with dalteparin in patients with active cancer and symptomatic or incidental PE, or symptomatic lower extremity proximal DVT. Patients were allocated to six months of rivaroxaban (15 mg twice daily for three weeks, then 20 mg once daily for a total of six months) or dalteparin (200 IU/kg daily during month one, then 150 IU/kg daily for months 2-6). The primary outcome was VTE recurrence over six months, and secondary safety outcomes were major bleeding and CRNMB. Exclusion criteria included high bleeding risk, platelet count <75 x 10⁹/L, creatinine clearance <30 mL/min, or life expectancy <3 months. Due to the high incidence of major bleeding, patients with malignant tumors of the esophagus or gastroesophageal junction were excluded from enrollment as a precautionary measure from the midpoint of the trial onwards. The trial was extended for a follow-up of 12 months. However, in this continuation of the SELECT-D trial, participants were newly randomized to rivaroxaban or placebo which was not the comparison of interest. Therefore, the 12 months publication of the SELECT-D trial was excluded (Marshall, 2020; see also exclusion table).

Raskob (2018) conducted the Hokusai VTE Cancer trial, a multinational, randomized, open label, noninferiority phase 3 trial in patients with active cancer and newly diagnosed acute symptomatic or incidental VTE. Participants were randomized to receive either edoxaban (60 mg once daily after at least five days of initial LMWH), or subcutaneous dalteparin (200 IU/kg for one month followed by 150 IU/kg daily). Patients with severe renal dysfunction, high bleeding risk, or brain tumors were excluded. In both groups, treatment was continued for at least six months, with a possible extension up to 12 months. Primary outcome was a composite of recurrence VTE or major bleeding. Secondary outcomes were the individual components recurrent VTE and major bleeding, and all-cause mortality.

McBane (2020) conducted the ADAM VTE-trial, a multicenter, open label, randomized trial in the United States. Adult patients, 18 years or older, with histologically confirmed active cancer and acute newly diagnosed VTE (symptomatic or incidental PE, proximal or distal upper or lower extremity DVT, splanchnic or cerebral vein thrombosis) were enrolled. Patients were randomized to receive apixaban (10 mg twice daily for seven days followed by 5 mg twice daily) or subcutaneous dalteparin (200 IU/kg for 1 month, followed by 150 IU/kg daily) for a total of six months. Exclusion criteria included ECOG PS >2, platelet count <50 x10⁹/L, or high bleeding risk. The primary safety outcome was any episode of major bleeding, secondary outcomes were any VTE recurrence, and a composite of major bleeding plus CRNMB.

Agnelli (2020) conducted the CARAVAGGIO-trial, a multinational, randomized, open label, noninferiority trial. Adult patients with active cancer and objectively confirmed newly diagnosed symptomatic or incidental proximal lower-limb DVT or PE (symptomatic or incidental) were enrolled. Participants were randomized to receive apixaban (10 mg twice daily for seven days followed by 5 mg twice daily) or dalteparin (200 IU/kg for one month followed by 150 IU/kg daily), for six months. Patients with brain tumors, platelet count <50 x10⁹/L, or high bleeding risk were excluded. Primary outcome was objectively confirmed recurrent VTE during the six-month trial period. The principal safety outcome was major bleeding.

Planquette (2022) conducted the CASTA-DIVA-trial, a multicenter, open-label, randomized controlled noninferiority trial performed in France. The study included adult patients with active cancer and objectively confirmed newly diagnosed VTE (symptomatic or incidental lower-limb DVT or inferior vena cava thrombosis, or PE, or both). Patients were randomized to receive rivaroxaban (15 mg twice daily for three weeks followed by 20 mg once daily) or dalteparin (200 IU/kg for one month then 150 IU/kg once daily) for a period of three months. Patients with ECOG performance status >2, significant thrombocytopenia (<75 x10⁹/L), or severe renal insufficiency were excluded. The primary efficacy outcome was a composite of recurrent VTE and worsening of pulmonary vascular or venous obstruction at three months. Secondary outcomes included symptomatic recurrences of PE or DVT, major bleeding events, a composite of major and CRNMB events, and all-cause mortality. Recruitment was stopped prematurely after 158 patients had been randomized, due to a slower-than-anticipated recruitment rate.

Schrag (2023) performed the CANVAS-trial, a multicenter, open label, noninferiority randomized comparative effectiveness study conducted across 67 oncology practices in the United States. Adult patients with active cancer and a new diagnosis of VTE (including symptomatic or asymptomatic PE or DVT) were eligible. Patients were randomized to receive either a DOAC (rivaroxaban, apixaban, or edoxaban, per physician’s choice) or LMWH. There were minimal exclusion criteria to reflect real-world practice. Outcomes were recurrence of nonfatal VTE, major bleeding, CRNMB, minor bleeding, mortality at six months, and health-related quality of life and participants’ perceptions of the burdens or benefits of anticoagulant treatment.

Table 2. Characteristics of included studies

Study	Participants	Comparison	Follow-up for primary outcome	Outcome measures	Comments	Risk of bias (per outcome measure)*
Young, 2018 (SELECT-D)	N=406 Intervention: 203 Median age: 67 (22-87) years Male sex: 116 (57%) Metastatic disease: 58% Control: 203 Median age: 67 (34-87) years Male sex: 98 (48%) Metastatic disease: 58%	Rivaroxaban (15 mg twice daily for 3 weeks followed by 20 mg once daily) vs. Dalteparin (200 IU/kg once daily for 1 month followed by 150 IU/kg once daily)	6 months	Primary: Recurrent VTE Secondary: Major bleeding and CRNMB	Pilot trial; open-label; industry-funded; Inclusion of esophagus or gastroesophageal junction tumors was stopped halfway due to high bleeding incidences	Some concerns (all outcomes)
Raskob, 2018 (Hokusai VTE Cancer)	N=1050 (analyzed = 1046) Intervention: 522 Mean age: 64.3 (11.) Male sex:: 277 (53.1%) Metastatic disease: 52.5% Control: 524 Mean age: 63.7 (11.7) Male sex: 263 (50.2%) Metastatic disease: 53.4%	Edoxaban (60 mg once daily after at least 5 days LMWH) vs. Dalteparin (200 IU/kg once daily for 1 month followed by 150 IU/kg once daily)	12 months	Primary: Composite of recurrent VTE or major bleeding Secondary: Recurrent VTE CRNMB Major or CRNMB Mortality Event-free survival	Open-label; industry-funded	High risk of bias (all outcomes)
McBane, 2020 (ADAM VTE)	N=300 (treated = 187) Intervention: 145 Mean age: 64.4 (11.3) years Male sex: 72 (48%) Metastatic disease: 65.3% Control: 142 Mean age: 64 (10.8) years Male sex: 73 (48.7%) Metastatic disease: 66%	Apixaban (10 mg twice daily for 7 days followed by 5 mg twice daily) vs. Dalteparin (200 IU/kg once daily for 1 month followed by 150 IU/kg once daily)	6 months	Primary: Major bleeding Secondary: Recurrent VTE or arterial thromboembolism CRNMB Major plus CRNMB Mortality	Open-label; small trial; industry-funded	Low risk of bias (all outcomes)
Agnelli, 2020 (CARAVAGGIO)	N=1155 Intervention: 576 Mean age: 67.2 (11.3) years Male sex: 292 (50.7%) Metastatic disease: 67.5% Control: 579 Mean age: 67.2 (10.9) years Male sex: 276 (47.7%) Metastatic disease: 68.4%	Apixaban (10 mg twice daily for 7 days followed by 5 mg twice daily) vs. Dalteparin (200 IU/kg once daily for 1 month followed by 150 IU/kg once daily)	6 months	Primary: Recurrent VTE Principal safety: Major bleeding Secondary: Recurrent VTE or major bleeding CRNMB Major bleeding or CRNMB Mortality Event-free survival	Open-label; noninferiority trial; partially industry-funded	Low risk of bias (all outcomes)
Planquette, 2022 (CASTA-DIVA)	N=158 Intervention: 74 Mean age: 68.6 (62.9-77.8) years Male sex: 37 (50%) Metastatic disease: 76.8% Control: 84 Mean age: 70.7 (62.7-78.7) years Male sex: 40 (47.6%) Metastatic disease: 75.6%	Rivaroxaban (15 mg twice daily for 3 weeks followed by 20 mg once daily) vs. Dalteparin (200 IU/kg once daily for 1 month followed by 150 IU/kg once daily)	3 months	Primary: Recurrent VTE Secondary: Major bleeding CRNMB Composite of major bleeding or CRNMB Mortality Symptomatic recurrent PE or DVT	Noninferiority criteria not met due to small sample	Low risk of bias (all outcomes)
Schrag, 2023 (CANVAS)	N=671 Intervention: 335 Median age: 64 (56-70) years Male sex: 149 (45%) Metastatic disease: 70% Control: 336 Median age: 62 (54-68) years Male sex: 111 (36%) Metastatic disease: 68%	DOAC (rivaroxaban (N=122; 37.0%), apixaban (N=193; 58.5%), dabigatran (N=9; 2.7%) or edoxaban (N=6; 1.8%), per physician’s choice) vs. LMWH (enoxaparin (N=277; 89.9%), fondaparinux (N=23; 7.5%),or dalteparin (N=8; 2.6%))	6 months	Primary: Recurrent nonfatal VTE Secondary: Bleeding: Major bleeding, CRNMB, or minor bleeding Mortality	Open-label; noninferiority trial; partially third party-funded	Low risk of bias (all outcomes)

_{*For further details, see risk of bias table in the appendix}

Results

The effect estimates were differently reported across studies; some studies reported a hazard ratio, others only the event numbers. In order to use all the available information, risk ratios (RR) were calculated based on the numbers provided in the studies.

Treatment duration 3-6 months

Recurrent VTE (critical)

Six studies (Young, 2018; Raskob, 2018; McBane, 2020; Agnelli, 2020; Planquette, 2022; Schrag, 2023) reported on the incidence of recurrent venous thromboembolism (VTE) in patients with active cancer receiving direct oral anticoagulants (DOACs) compared with low-molecular-weight heparin (LMWH) for initial treatment of acute VTE. The studies evaluated rivaroxaban, edoxaban, apixaban, or various DOACs per physician’s discretion.

The results were estimated with RRs. The number of events and number of randomized participants was used to calculate the RRs. The pooled analysis showed that the risk of a recurrent VTE decreased (clinically relevant) with the use of a DOAC compared with LMWH (RR 0.66; 95%CI 0.50 to 0.87; Figure 1).

_{Figure 1. Meta-analysis on the effect of initial treatment of acute VTE in patients with active cancer with DOAC compared to treatment with LMWH, on the outcome recurrent VTE}

_{DOAC: direct oral anticoagulants, LMWH: low molecular weight heparin}

Major bleeding (critical)

Six studies (Young, 2018; Raskob, 2018; McBane, 2020; Agnelli, 2020; Planquette, 2022; Schrag, 2023) reported on the incidence of major bleeding in patients with active cancer receiving DOACs compared with LMWH for initial treatment of acute VTE. One study (McBane, 2020; ADAM-VTE trial) reported no major bleeding events in DOAC-group and two events in the LMWH-group. No effect estimate was calculated for this study.

The results were estimated with RRs. The number of events and number of randomized participants was used to calculate the RRs. The pooled analysis showed that the risk of a major bleeding was similar (no clinically relevant difference) with the use of a DOAC compared with LMWH (RR 1.22; 95%CI 0.74 to 2.00; Figure 2).

_{Figure 2. Meta-analysis on the effect of initial treatment of acute VTE in patients with active cancer with DOAC compared to treatment with LMWH, on the outcome major bleeding}

_{DOAC: direct oral anticoagulants, LMWH: low molecular weight heparin}

Mortality (critical)

Six studies (Young, 2018; Raskob, 2018; McBane, 2020; Agnelli, 2020; Planquette, 2022; Schrag, 2023) reported on the incidence of all-cause mortality in patients with active cancer receiving DOACs compared to LMWH for initial treatment of acute VTE.

The results were estimated with RRs. The number of events and number of randomized participants was used to calculate the RRs. The pooled analysis showed that the risk of mortality was similar (no clinically relevant difference) with the use of a DOAC compared with LMWH (RR 1.02; 95%CI 0.87 to 1.19, Figure 3).

_{Figure 3. Meta-analysis on the effect of initial treatment of acute VTE in patients with active cancer with DOAC compared to treatment with LMWH, on the outcome mortality}

_{DOAC: direct oral anticoagulants, LMWH: low molecular weight heparin}

Clinically relevant non-major bleeding (CRNMB) (important)

Six studies (Young, 2018; Raskob, 2018; McBane, 2020; Agnelli, 2020; Planquette, 2022; Schrag, 2023) reported on the incidence of clinically relevant non-major bleeding (CRNMB) in patients with active cancer receiving DOACs compared with LMWH for initial treatment of acute VTE.

The results were estimated with RRs. The number of events and number of randomized participants was used to calculate the RRs. The pooled analysis showed that the risk of a CRNMB was increased (clinically relevant) with the use of a DOAC compared with LMWH (RR 1.60; 95%CI 1.13 to 2.28, Figure 4).

_{Figure 4. Meta-analysis on the effect of initial treatment of acute VTE in patients with active cancer with DOAC compared to treatment with LMWH, on the outcome clinically relevant non-major bleeding}

_{DOAC: direct oral anticoagulants, LMWH: low molecular weight heparin}

Net clinical benefit (important)

One study (Raskob, 2018) reported a net clinical benefit (a composite of recurrent VTE or major bleeding) in patients with active cancer receiving edoxaban compared with dalteparin for initial treatment of acute VTE. The reported HR was 0.97 (95%CI 0.70 to 1.36), which is not a clinically relevant difference.

Treatment duration > 6 months

No trial was included on the effect of treatment with DOACs beyond the initial six months, compared to LMWH-treatment in patients with acute cancer-associated VTE.

Zoeken en selecteren

A systematic review of the literature was performed to answer the following question(s):

What is the efficacy and safety of direct oral anticoagulants (DOACs) compared to low-molecular-weight heparin (LMWH) in patients with cancer-associated VTE (i.e., deep vein thrombosis (DVT) of the leg and/or pulmonary embolism (PE)), for (a) the initial treatment period (first 3–6 months), and (b) the long-term treatment period (beyond 6 months)?

Table 1. PICO

Patients	Adults with acute cancer-associated venous thromboembolism (VTE, i.e. DVT of the leg and/or PE)
Intervention	Anticoagulant therapy with direct oral anticoagulants (DOACs)
Control	Anticoagulant therapy with low-molecular-weight heparin (LMWH)
Outcomes	Mortality, recurrent VTE, major bleeding, net clinical benefit, clinically relevant non-major bleeding (CRNMB)
Other selection criteria	Study design: systematic reviews and randomized controlled trials
Planned analyses	Analyses will be separated by the duration of treatment (3-6 months versus > 6 months) If the pooled analysis shows indications of heterogeneity, a subgroup analysis by type of DOAC will be performed

Relevant outcome measures

The guideline panel considered mortality, recurrent VTE and major bleeding as critical outcome measures for decision making; and net clinical benefit and CRNMB as important outcome measures for decision making.

A priori, the guideline panel did not define the outcome measures listed above but used the definitions used in the studies.

The definition of active malignancy differs in the literature and between studies, but roughly was as follows:

a diagnosis of (recurrent) cancer (excluding basal cell carcinoma or squamous cell carcinoma of the skin) in the past 6 months;
up to 6 months after the last anti-cancer treatment;
the presence of a known chronic malignant condition (such as chronic myeloid/ lymphoid leukemia or multiple myeloma) or
the presence of known metastatic disease, regardless of whether the patient is in a (terminal) palliative phase.

The guideline panel defined a relative risk of ≤ 0.80 or ≥ 1.25 as the threshold for a minimal clinically important difference across all outcome measures. These criteria were applied to both hazard ratios (HR) and odds ratios (OR).

Search and select (Methods)

In 2020 the module Treatment of cancer-associated thrombosis was updated. A systematic literature update was performed by a medical information specialist searching the following bibliographic databases on 23 April 2018 for systematic reviews and RCTs: Medline (via PubMed), Embase (via Ovid), Web of Science, The Cochrane Library en Academic Search Premier. Initially, 28 studies were selected based on title and abstract screening. After reading the full text, 25 studies were excluded (see the exclusion table under the tab ‘Evidence tabellen’), and three studies were included: two RCTs (Raskob, 2018; Young, 2018) and one systematic literature review (Li, 2018). Dose-finding studies (phase 2 trials) and studies on primary prophylaxis of VTE in cancer patients were excluded. Since the review of Li (2018) only included the studies of Raskob (2018) and Young (2018) and some additional non-randomized studies, the literature analysis focused on the studies of Raskob (2018) and Young (2018).

In this 2024 update, a systematic literature update was performed by a medical information specialist using the following bibliographic databases: Embase.com and Ovid/Medline. Both databases were searched from January 2018 to 17 October 2024 for systematic reviews and RCTs. Systematic searches were completed using a combination of controlled vocabulary/subject headings (e.g., Emtree-terms, MeSH) wherever they were available and natural language keywords. Duplicates were removed using EndNote software. After deduplication a total of 1232 records were imported for title/abstract screening. Initially, 27 studies were selected based on title and abstract screening. After reading the full text, 23 studies were excluded (see the exclusion table under the tab ‘Evidence tabellen’), and four additional studies were included (McBane, 2020; Agnelli, 2020; Planquette, 2022 and Schrag, 2023). Dose-finding studies (phase 2 trials), comparisons between two doses of DOACs and studies on primary prophylaxis of VTE in cancer patients were excluded.

Referenties

Agnelli G, Becattini C, Meyer G, Muñoz A, Huisman MV, Connors JM, Cohen AT, Lee AYY, Gallus AS, Johnson M, Porreca E, Bauersachs R. Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. N Engl J Med. 2020 Apr 23;382(17):1599-1607. doi: 10.1056/NEJMoa1915103. PMID: 32320557.
van Es N, Coppens M, Schulman S, Middeldorp S, Büller HR. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood. 2014 Sep 18;124(12):1968-75. doi: 10.1182/blood-2014-04-571232. Epub 2014 Jun 24. PMID: 24963045.
van der Hulle T, den Exter PL, Kooiman J, van der Hoeven JJ, Huisman MV, Klok FA. Meta-analysis of the efficacy and safety of new oral anticoagulants in patients with cancer-associated acute venous thromboembolism. J Thromb Haemost. 2014 Jul;12(7):1116-20. doi: 10.1111/jth.12605. Epub 2014 Jun 19. PMID: 24819040.
Hutchinson A, Rees S, Young A, Maraveyas A, Date K, Johnson MJ. Oral anticoagulation is preferable to injected, but only if it is safe and effective: An interview study of patient and carer experience of oral and injected anticoagulant therapy for cancer-associated thrombosis in the select-d trial. Palliat Med. 2019 May;33(5):510-517. doi: 10.1177/0269216318815377. Epub 2018 Nov 29. PMID: 30488789; PMCID: PMC6506899.
Kahale LA, Tsolakian IG, Hakoum MB, Matar CF, Barba M, Yosuico VE, Terrenato I, Sperati F, Schünemann H, Akl EA. Anticoagulation for people with cancer and central venous catheters. Cochrane Database Syst Rev. 2018 Jun 1;6(6):CD006468. doi: 10.1002/14651858.CD006468.pub6. PMID: 29856471; PMCID: PMC6389340.
Mahé I, Carrier M, Mayeur D, Chidiac J, Vicaut E, Falvo N, Sanchez O, Grange C, Monreal M, López-Núñez JJ, Otero-Candelera R, Le Gal G, Yeo E, Righini M, Robert-Ebadi H, Huisman MV, Klok FA, Westerweel P, Agnelli G, Becattini C, Bamias A, Syrigos K, Szmit S, Torbicki A, Verhamme P, Maraveyas A, Cohen AT, Ay C, Chapelle C, Meyer G, Couturaud F, Mismetti P, Girard P, Bertoletti L, Laporte S; API-CAT Investigators. Extended Reduced-Dose Apixaban for Cancer-Associated Venous Thromboembolism. N Engl J Med. 2025 Apr 10;392(14):1363-1373. doi: 10.1056/NEJMoa2416112. Epub 2025 Mar 29. PMID: 40162636.
McBane RD, Wysokinski WE, Le-Rademacher JG, Nahhas GJ, Ashrani AA, Tafur A, McCrae KR, Milhem M, Kolesar J, Wieben ED, Khorana AA. Apixaban and Dalteparin in Active Malignancy–Associated Venous Thromboembolism: The ADAM VTE Trial. J Thromb Haemost. 2020 Nov;18(11):4115-4123. doi: 10.1111/jth.15002. PMID: 32686279.
McBane RD 2nd, Loprinzi CL, Zemla T, Tafur A, Sanfilippo K, Liu JJ, Garcia DA, Heun J, Gundabolu K, Onitilo AA, Perepu U, Drescher MR, Henkin S, Houghton D, Ashrani A, Billett H, McCue SA, Lee MK, Le-Rademacher JG, Wysokinski WE; EVE trial investigators. Extending venous thromboembolism secondary prevention with apixaban in cancer patients. The EVE trial. J Thromb Haemost. 2024 Jun;22(6):1704-1714. doi: 10.1016/j.jtha.2024.03.011. Epub 2024 Mar 25. Erratum in: J Thromb Haemost. 2025 Feb;23(2):756. doi: 10.1016/j.jtha.2024.12.011. PMID: 38537780.
Planquette B, Faille D, Doubine S, Canet E, Lemarié C, Doubovetzky M, Chatellier G, Sanchez O. Rivaroxaban vs Dalteparin in Cancer-Associated Thromboembolism: A Randomized Trial. Chest. 2022 Jun;161(6):1571-1580. doi: 10.1016/j.chest.2021.11.018. PMID: 34875463.
Posch F, Königsbrügge O, Zielinski C, Pabinger I, Ay C. Treatment of venous thromboembolism in patients with cancer: A network meta-analysis comparing efficacy and safety of anticoagulants. Thromb Res. 2015 Sep;136(3):582-9. doi: 10.1016/j.thromres.2015.07.011. Epub 2015 Jul 17. PMID: 26210891; PMCID: PMC7311195.
Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Segers A, Shi M, Wang TF, Weitz JI, Büller HR; Hokusai VTE Cancer Investigators. Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism. N Engl J Med. 2018 Feb 15;378(7):615-624. doi: 10.1056/NEJMoa1711948. PMID: 29231094.
Schrag D, Lin GA, Goldhaber SZ, Sanoff HK, Bhatia S, Hudis C, Meara E, Shah N, Rivest A, Trivedi A, Finkelstein DM. Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin and Recurrent VTE in Patients with Cancer: A Randomized Clinical Trial. JAMA. 2023 Aug 1;330(5):425–434. doi:10.1001/jama.2023.12515. PMID: 37523463.
Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, Hale D, Dunn JA, Lyman GH, Hutchinson C, MacCallum P, Kakkar A, Hobbs FDR, Petrou S, Dale J, Poole CJ, Maraveyas A, Levine M. Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D). J Clin Oncol. 2018 Jul 10;36(20):2017-2023. doi: 10.1200/JCO.2018.78.8034. PMID: 29746227.

Evidence tabellen

Risk of Bias tables

Study reference	Was the allocation sequence adequately generated?	Was the allocation adequately concealed?	Blinding: Was knowledge of the allocated interventions adequately prevented? Were patients/healthcare providers/data collectors/outcome assessors/data analysts blinded? Were patients blinded?	Was loss to follow-up (missing outcome data) infrequent?	Are reports of the study free of selective outcome reporting?	Was the study apparently free of other problems that could put it at a risk of bias?	Overall risk of bias
Young, 2018	Definitely yes – “Consenting patients were randomly assigned at a one-to-one ratio using a computer-based minimization algorithm with stratification by stage of disease, baseline platelet count, type of VTE, and risk of clotting by tumor type.”	Definitely yes – Secure allocation process used across sites.	Probably yes – Open-label design “Trial staff, participants, and investigators were not blinded to treatment allocation.” An independent committee of experienced clinicians unaware of treatment allocation adjudicated all the outcomes.	Definitely yes	Definitely yes	Probably no Although the trial was sponsored by the industry, the grant was unrestricted and the sponsor had no conduct in the design, data analysis, etc. However, after a safety analysis showing a nonsignificant difference in major bleeding, the enrollment of patients with esophagus or gastroesophageal cancer was stopped.	Some concerns - for all outcomes Due to the exclusion of some patients halfway through the study.
Raskob, 2018	Definitely yes – “Randomization was performed with the use of an interactive Web-based system, with stratification according to whether risk factors for bleeding were present and whether the patient met the criteria to receive a lower dose of edoxaban.”	Definitely yes – Allocation concealment via web system.	Definitely yes – Blinded outcome adjudication committee ensured unbiased assessment.	Definitely yes	Definitely yes	Definitely no The trial was sponsored by industry and was heavily involved in every aspect of the trial.	High Risk of bias – all outcome Due to industry sponsor being heavily involved in every aspect of the trial.
McBane, 2020	Definitely yes – Randomized controlled trial with clear procedure. Stratification factors used for randomization include cancer stage and cancer specific risk of venous thromboembolism using the Khorana score.	Probably yes – Randomization mentioned, but concealment method unclear.	Probably yes – Open-label design with no blinding for bleeding outcomes. Major bleeding and thrombotic events were centrally adjudicated without knowledge of the patient treatment assignment. Although CRNMB was not blinded adjudicated, there is a clear definition for this outcome.	Definitely yes	Definitely yes	Probably yes The trial received a grant from the industry. Most likely the sponsor had no influence on the design, etc. because the authors stated: “The primary investigator, in collaboration with the Academic and Community Cancer Research United (ACCRU) research consortium, was responsible for the trial design, protocol development, data collection, statistical analysis, data interpretation, manuscript preparation, and trial oversight.”	Low Risk of bias - for all outcomes
Agnelli, 2020	Definitely yes – Computer-generated random sequence with stratification stratified according to the type of venous thromboembolism (symptomatic or incidental) and timing of the cancer diagnosis (active or historical).	Definitely yes – Centralized randomization via interactive web system ensured concealment.	Probably yes – Outcomes assessed by blinded committee, but open-label design may influence patient behavior. Comment by authors on blinding: “double-blinding would have required daily subcutaneous injection of placebo in the apixaban recipients. Ethically, the use of daily injectable placebo and the related inconvenience for patients that already need complex treatment for cancer are difficult to justify.”	Definitely yes – Low loss to follow-up; outcomes assessed for nearly all randomized patients.	Definitely yes	Definitely yes Although the trial was sponsored by the industry, the grant was unrestricted and the sponsor had no conduct in the design, data analysis, etc.	Low Risk of bias - for all outcomes
Planquette, 2022	Definitely yes – “Randomization was performed centrally through an interactive web response system (CleanWeb) and was stratified according to center and disease stage (localized or locally advanced vs metastatic).”	Definitely yes – Allocation sequence concealed through electronic system.	Definitely yes – Blinded central adjudication committee assessed outcomes.	Definitely yes	Definitely yes	Definitely yes Trial was supported by an unrestricted grant from the industry.	Low Risk of bias - for all outcomes
Schrag, 2023	Definitely yes – Randomization process and blocking per site clearly described.	Definitely yes – Concealment ensured through central assignment.	Definitely yes - Treating physician was blinded to group assignment. Outcomes were adjudicated blinded to group assignment for all outcomes.	Definitely yes	Definitely yes	Definitely yes – Non-industry sponsor was not involved in the design, analysis, etc.	Low Risk of bias - for all outcomes

Table of excluded studies 2024

Reference	Reason for exclusion
Ageno W, Vedovati MC, Cohen A, Huisman M, Bauersachs R, Gussoni G, Becattini C, Agnelli G. Bleeding with Apixaban and Dalteparin in Patients with Cancer-Associated Venous Thromboembolism: Results from the Caravaggio Study. Thromb Haemost. 2021 May;121(5):616-624. doi: 10.1055/s-0040-1720975. Epub 2020 Nov 17. PMID: 33202447.	Post-hoc analysis of original RCT (Agnelli 2020)
Agnelli G, Muñoz A, Franco L, Mahé I, Brenner B, Connors JM, Gussoni G, Hamulyak EN, Lambert C, Suero MR, Bauersachs R, Torbicki A, Becattini C. Apixaban and Dalteparin for the Treatment of Venous Thromboembolism in Patients with Different Sites of Cancer. Thromb Haemost. 2022 May;122(5):796-807. doi: 10.1055/s-0041-1735194. Epub 2021 Sep 16. PMID: 34530482.	Post-hoc analysis of original RCT (Agnelli 2020)
Al-Mansouri L, AL-Obaidi FR, Altaweel RB, Soto-Perez-de-Celis E, Al-Farhan H, Abdullah NA, Alrubaiy L. Direct oral anticoagulants for the prevention and treatment of venous thromboembolic events in cancer patients: a meta-analysis of randomized controlled trials. J Cancer Prev Curr Res. 2024;20(1):100–105. Published 2023 May 19.	Not a primary study
Al-Tourah L, Mithoowani S, Lim W, Ikesaka R. The incidence of major bleeding in adult patients with urogenital and gynecological cancer being treated with direct oral anticoagulants (DOACs): a systematic review. J Thromb Thrombolysis. 2024 Apr;57(4):630-637. doi: 10.1007/s11239-024-02956-5. Epub 2024 Mar 1. PMID: 38429468.	Not a primary study
Alikhan R, Gomez K, Maraveyas A, Noble S, Young A, Thomas M; British Society for Haematology. Cancer-associated venous thrombosis in adults (second edition): A British Society for Haematology Guideline. Br J Haematol. 2024 Jul;205(1):71-87. doi: 10.1111/bjh.19414. Epub 2024 Apr 25. PMID: 38664942.	Not a primary study, guideline
Bosch FTM, Mulder FI, Huisman MV, Zwicker JI, Di Nisio M, Carrier M, Segers A, Verhamme P, Middeldorp S, Weitz JI, Grosso MA, Duggal A, Büller HR, Wang TF, Garcia D, Kamphuisen PW, Raskob GE, van Es N. Risk factors for gastrointestinal bleeding in patients with gastrointestinal cancer using edoxaban. J Thromb Haemost. 2021 Dec;19(12):3008-3017. doi: 10.1111/jth.15516. Epub 2021 Sep 12. PMID: 34455706; PMCID: PMC9292167.	Did not adhere to PICO
Chatani R, Yamashita Y, Morimoto T, Muraoka N, Umetsu M, Nishimoto Y, Takada T, Ogihara Y, Nishikawa T, Ikeda N, Otsui K, Sueta D, Tsubata Y, Shoji M, Shikama A, Hosoi Y, Tanabe Y, Tsukahara K, Nakanishi N, Kim K, Ikeda S, Mushiake K, Kadota K, Ono K, Kimura T. Edoxaban for 12 vs. 3 months in cancer-associated isolated distal deep vein thrombosis according to different doses: insights from the ONCO DVT study. Eur Heart J Cardiovasc Pharmacother. 2024 Aug 14;10(5):422-431. doi: 10.1093/ehjcvp/pvae028. PMID: 38650055; PMCID: PMC11323369.	Post-hoc analysis of Yamashita 2023
Chaudhury A, Balakrishnan A, Thai C, Holmstrom B, Nanjappa S, Ma Z, Jaglal MV. The Efficacy and Safety of Rivaroxaban and Dalteparin in the Treatment of Cancer Associated Venous Thrombosis. Indian J Hematol Blood Transfus. 2018 Jul;34(3):530-534. doi: 10.1007/s12288-017-0895-8. Epub 2017 Oct 27. PMID: 30127566; PMCID: PMC6081306.	Did not adhere to PICO
Cohen AT, Creeper KJ, Alikhan R, Er C, Connors JM, Huisman MV, Munoz A, Vescovo G, Bauersachs R, Ageno W, Agnelli G, Becattini C. Early Time Courses of Recurrent Venous Thromboembolism and Bleeding during Apixaban or Dalteparin Therapy for Patients with Cancer. Thromb Haemost. 2024 Jul;124(7):676-683. doi: 10.1055/s-0043-1778642. Epub 2024 Jan 9. PMID: 38196077.	Secondary publication of Agnelli (2020)
Di Nisio M, van Es N, Carrier M, Wang TF, Garcia D, Segers A, Weitz J, Buller H, Raskob G. Extended treatment with edoxaban in cancer patients with venous thromboembolism: A post-hoc analysis of the Hokusai-VTE Cancer study. J Thromb Haemost. 2019 Nov;17(11):1866-1874. doi: 10.1111/jth.14561. Epub 2019 Jul 25. PMID: 31271705.	Secondary publication of Raskob (2018)
Grifoni E, Baroncelli A, Pinto G, Cosentino E, Micheletti I, Signorini I, Panigada G, Landini G, Masotti L. Efficacy and Safety of Edoxaban in Cancer-Associated Venous Thromboembolism: A Real World Retrospective Study. TH Open. 2022 Mar 1;6(2):e99-e106. doi: 10.1055/a-1783-9744. PMID: 35707622; PMCID: PMC9113858.	Did not adhere to PICO (not a randomized controlled trial)
Kraaijpoel N, Di Nisio M, Mulder FI, van Es N, Beyer-Westendorf J, Carrier M, Garcia D, Grosso M, Kakkar AK, Mercuri MF, Middeldorp S, Hernandez CR, Santamaria A, Schwocho L, Segers A, Verhamme P, Wang TF, Weitz JI, Zhang G, Zwicker JI, Büller HR, Raskob GE. Clinical Impact of Bleeding in Cancer-Associated Venous Thromboembolism: Results from the Hokusai VTE Cancer Study. Thromb Haemost. 2018 Aug;118(8):1439-1449. doi: 10.1055/s-0038-1667001. Epub 2018 Jul 30. PMID: 30060256.	Secondary publication of Raskob (2018)
Mahe I, Muñoz A, Cohen A, Raskob G, Mahé I, Bauersachs R, Vedovati MC, Brenner B, Connors JM, Gussoni G, Huisman MV, Suero MR, Torbicki A, Agnelli G, Becattini C. Reduced-dose versus full-dose apixaban in cancer patients with venous thromboembolism: the API-CAT non-inferiority randomized trial. Lancet Haematol. 2025 Feb;10(2):e99-e109. doi: 10.1016/S2352-3026(24)00012-7. PMID: 38435012.	Dose comparison trial for extended VTE treatment with apixaban
Marshall A, Campbell C, Hill C, Hale D, Thirlwall J, Parpia S, Maraveyas A, Poole C, Levine M, Young AM. Treatment of cancer-associated venous thromboembolism: 12-month outcomes of the placebo versus rivaroxaban randomization of the SELECT-D Trial (SELECT-D: 12m). J Thromb Haemost. 2020 May;18(5):905-915. doi: 10.1111/jth.14740. PMID: 32087556.	Compared with placebo, not LMWH
McBane RD, Tafur A, Le-Rademacher JG, Fashanu OE, Khorana AA, Lyman GH, Milhem M, McCrae KR, Wysokinski WE, Ashrani AA. Extending venous thromboembolism secondary prevention with apixaban in cancer patients: The EVE randomized clinical trial. J Thromb Haemost. 2024 Jan;22(1):97-108. doi: 10.1111/jth.16585. PMID: 37816545.	Dose comparison trial for extended VTE treatment with apixaban
Moik F, Colling M, Mahé I, Jara-Palomares L, Pabinger I, Ay C. Extended anticoagulation treatment for cancer-associated thrombosis-Rates of recurrence and bleeding beyond 6 months: A systematic review. J Thromb Haemost. 2022 Mar;20(3):619-634. doi: 10.1111/jth.15599. Epub 2021 Dec 8. PMID: 34816583; PMCID: PMC9299994.	Not a primary study
Mokadem ME, Hassan A, Algaby AZ. Efficacy and safety of apixaban in patients with active malignancy and acute deep venous thrombosis. Vascular. 2021 Oct;29(5):745-750. doi: 10.1177/1708538120971148. Epub 2020 Nov 5. PMID: 33153401.	Not randomized or comparative
Palumbo JS, Lensing AWA, Brandão LR, Hooimeijer HL, Kenet G, van Ommen H, Pap AF, Majumder M, Kubitza D, Thelen K, Willmann S, Prins MH, Monagle P, Male C. Anticoagulation in pediatric cancer-associated venous thromboembolism: a subgroup analysis of EINSTEIN-Jr. Blood Adv. 2022 Nov 22;6(22):5821-5828. doi: 10.1182/bloodadvances.2022008160. PMID: 36006613; PMCID: PMC9641171.	Pediatric population, not adult
Pina E, Antonio M, Peris J, Rosselló E, Domènech P, Peñafiel J, Tebe C. Bemiparin as a long-term treatment for venous thrombosis in cancer patients: the ELEBAMA study. Clin Transl Oncol. 2020 Apr;22(4):616-620. doi: 10.1007/s12094-019-02159-y. Epub 2019 Jun 19. PMID: 31218649.	Did not adhere to PICO
Ullah F, Song J, Rojas Hernandez CM, Kroll MH, Escalante CP, Toale KM. Safety and Effectiveness of Direct Oral Anticoagulants for the Treatment of Gastrointestinal Cancer-Associated Venous Thromboembolism. Oncologist. 2023 Nov 2;28(11):e1005-e1016. doi: 10.1093/oncolo/oyad148. PMID: 37310796; PMCID: PMC10628557.	Wrong study design
Tia JM, Casapao JC, Liangco W, Gaspar-Trinidad E. Treatment efficacy and risk of bleeding among cancer patients treated for venous thromboembolism with dabigatran compared to warfarin. Phil J Intern Med. 2018;56:252–257.	Did not adhere to PICO
Yamashita Y, Morimoto T, Amano H, Hasegawa K, Okabe H, Tsubata Y, Nishimoto Y, Umetsu M, Takase T, Muraoka N, Ikeda S, Fukuda K. Edoxaban for 12 Months Versus 3 Months in Patients with Cancer with Isolated Distal Deep Vein Thrombosis (ONCO DVT Study): An Open-Label, Multicenter, Randomized Clinical Trial. JAMA Intern Med. 2023 Oct 1;183(10):1056-1064. doi: 10.1001/jamainternmed.2023.3764. PMID: 37627168.	Comparison between two durations of treatment with edoxaban.

Table of excluded studies 2018

Author, year	Reason for exclusion
Van der Hulle 2014	Meta-analysis DOAC versus VKA
Carrier 2014	No comparison between DOAC and LMWH
Di Minno 2017	Meta-analysis DOAC versus VKA
Brunetti 2017	Meta-analysis DOAC versus VKA
Posch 2015	Meta-analysis DOAC versus VKA
Vedovati 2015	Meta-analysis DOAC versus VKA
Larsen 2014	Meta-analysis DOAC versus VKA
Van En 2014	Meta-analysis DOAC versus VKA
Schulman 2016	Meta-analysis DOAC versus VKA
Agnelli 2015	Non-randomized study
Bott-Kitslaar 2016	Non-randomized study
Davies 2018	Non-randomized study
Mancuso 2016	Non-randomized study
Mantha 2017	Non-randomized study
Raskob 2016	Non-randomized study
Schulman 2015	Non-randomized study
Simmons 2018	Non-randomized study
Alzghari 2017	Non-randomized study
Streiff 2018	Non-randomized study
Ross 2017	Non-randomized study
Xiang 2018	Non-randomized study
Hirsh 2018	Editorial
Lee 2018	Narrative review
Noble 2016a	Narrative review
Noble 2016b	Narrative review

Verantwoording

Beoordelingsdatum en geldigheid

Publicatiedatum : 01-05-2026

Beoordeeld op geldigheid : 01-05-2026

Initiatief en autorisatie

Initiatief:

Cluster Antitrombotisch beleid

Geautoriseerd door:

Nederlandse Internisten Vereniging
Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose
Nederlandse Vereniging van Ziekenhuisapothekers
Hartstichting

Samenstelling werkgroep

Voor het ontwikkelen van de richtlijnmodule is in 2022 een multidisciplinaire cluster ingesteld. Het cluster Antitrombotisch beleid bestaat uit meerdere richtlijnen, zie hier voor de actuele clusterindeling. De stuurgroep bewaakt het proces van modulair onderhoud binnen het cluster. De expertisegroepsleden geven hun expertise in, indien nodig. De volgende personen uit het cluster zijn betrokken geweest bij de herziening van deze module:

Clusterstuurgroepleden

Prof. dr. M.V. (Menno) Huisman, internist-vasculaire geneeskunde, LUMC, NIV (voorzitter)
Dr. M.J.H.A. (Marieke) Kruip, internist-hematoloog, Erasmus MC, NIV, NVVH (Nederlandse Vereniging voor Hematologie)
Dr. S.H. (Steven) Renes, anesthesioloog, Radboudumc, NVA
Dr. L.M. (Linda) de Heer, cardiothoracaal chirurg, UMC Utrecht, NVT
Dr. A.K. Stroobants, klinisch chemicus, Radboudumc, NVKC
Drs. E. (Egbert) Krug, traumachirurg, LUMC, NVvH
Dr. H.B. (Harmen) Ettema, orthopedisch chirurg, Isala, NOV
Dr. B. (Banne) Nemeth, aios orthopedie, LUMC, NOV
Dr. M.E. (Maarten) Tushuizen, maag-darm-leverarts, LUMC, NVMDL
Dr. C.H. (Heleen) van Ommen, kinderarts-hematoloog, Erasmus MC, NVK
Dr. E.J. (Esther) Nossent, longarts, Amsterdam UMC, NVALT
Dr. N. (Nakisa) Khorsand, ziekenhuisapotheker, OLVG, NVZA
Dr. S.A. (Sonja) de Munnik, klinisch geneticus, Radboudumc, VKGN

Betrokken clusterexpertisegroepleden

Dr. M.N. (Mandy) Lauw, internist-hematoloog, Erasmus MC, NIV, NVVH (Nederlandse Vereniging voor Hematologie)
Prof. Dr. F.A. (Erik) Klok, internist-vasculaire geneeskunde, LUMC, NIV

Meelezende clusterexpertisegroepleden

Dr. J. (Josien) van Es, longarts, Amsterdam UMC, NVALT

Met ondersteuning van

H. (Hanneke) Olthuis, adviseur, Kennisinstituut van de Federatie Medisch Specialisten (tot 1 februari 2026)
Dr. B.H. (Bernardine) Stegeman, senior adviseur, Kennisinstituut van de Federatie Medisch Specialisten
E. (Esther) van der Bijl, Informatiespecialist, Kennisinstituut van de Federatie Medisch Specialisten

Belangenverklaringen

Een overzicht van de belangen van de clusterleden en het oordeel over het omgaan met eventuele belangen vindt u in onderstaande tabel. De ondertekende belangenverklaringen zijn op te vragen bij het secretariaat van het Kennisinstituut van de Federatie Medisch Specialisten via secretariaat@kennisinstituut.nl.

Tabel Gemelde (neven)functies en belangen stuurgroepleden en betrokken clusterexpertisegroepleden

Naam	Hoofdfunctie	Nevenwerkzaamheden	Persoonlijke financiële belangen	Persoonlijke relaties	Extern gefinancierd onderzoek	Intellectuele belangen en reputatie	Overige belangen	Restrictie
Stuurgroepleden
*Huisman (vz)*	internist LUMC Leiden	Voorzitter nederlands kennisplatform antistollingszorg onbetaald; board of directors PERT USA onbetaald	geen	geen	Hartstichting, COVID en herseninfarct, projectleider ja; ZonMw register atriumfibrilleren, projectleider ja; BI, register AF -afgerond, register af, - afgerond; Bayer, register VTE en Kanker, projectleider ja – afgerond; Leo Pfizer-BMS, register VTE en kanker, projectleider ja - afgerond	nee	nvt	Geen restricties
*Ettema*	Orthopedisch chirurg Isala Zwolle	Geen	Geen	Geen	Geen	Geen	Geen	Geen restricties (in 2025 geen herbevestiging ontvangen)
*de Heer*	Cardio-thoracaal chirurg UMC Utrecht	Geen	Geen	Geen	Geen	Geen	Geen	Geen restricties
*Stroobants*	Klinisch chemicus RadboudUMC	Bestuur vakvereniging VHL (secretaris, onbetaald), Werkgroep hemostase VHL (voorzitter, onbetaald), Sectie stolling van de SKML (voorzitter, onbetaald), Advisory board ECAT (onbetaald); RvT ECAT (betaald, aan RadboudUMC)	Dienstverband RadboudUMC	n.v.t.	n.v.t.	Geen	n.v.t.	Geen restricties
*Tushuizen*	MDL-arts LUMC	lid Horizonscan Geneesmiddelen, onbetaald	Geen	Geen	TNO, markers voor fibrose, rol als projectleider	Geen	Geen	Geen restricties
*Khorsand*	Ziekenhuisapotheker OLVG	Voorzitter SIG hematologie NVZA (onbetaald); Voorzitter programma commissie congres NVZA (onbetaald)	Geen	Geen	Geen	Geen	Geen	Geen restricties
*Kruip*	Hematoloog Erasmus MC (0.3 FTE) Directier Kwaliteite en Patiëntenzorg Erasmus MC (0.7 FTE)	Voorzitter Federatie Nederlandse trombosediensten, onbetaald (afgerond); Bestuur Nederlandse Vereniging voor Trombose en hemostase, onbetaald (afgerond); RvT Trombosestichting Nederland, onbetaald; RvC Lenticure, onbetaald; Lid guideline committee European Hematology Association, onbetaald	Geen	Geen	ZonMw en Trombosestichting NL, Trombose bij Covid 19 (afgerond); ZonMw, VITT na Coronavaccinatie (afgerond); FNT, coronavaccinatie bij VKA (afgerond); Sobi, DDAVP bij milde hemof (afgerond); Trombosestichting NL - Antiplatelet Therapy and menstrual blood loss; PARASOL study (Projectleider JA); Horizon Europe - SERENITY: Improved supportive, palliative, survivorship and end-of-life care of cancer patients (Local PI); Zorginstituut, Recognition and registration of low health literary in patients with diabetes to enable shared decision making (Projectleider NEE); ZonMW, Bloedstollend veilig: Safety-II education focused on anticoagulants in master of Medicine (Projectleider NEE); Citrienfonds, Inclusieve zorg voor mensen met geldzorgen in digitale tijden (projectleider NEE)	Geen	Sprekersvergoeding, betaald aan het Erasmus MC van Sobi, Roche en BMS (afgerond)	Geen restricties (onderwerp van commercieel gefinancieerd onderzoek valt buiten bestek van deze cyclus)
*Renes*	Anesthesioloog-pijnspecialist, RadboudUMC (betaald)	Kwaliteitsvisitatie NVA (vacatiegeld) Medische expertise op persoonlijke titel (betaald)	geen	geen	Geen	geen	geen	Geen restricties
*van Ommen*	Hoofd afd. Kinderhematologie & kinderoncologie Erasmus MC Sophia Kinderziekenhuis	Geen	geen	Geen	Fase 3 trial effectiviteit van edoxaban voor behandeling van trombose bij kinderen, financier Daiichi Sankyo, local PI en steeringCie (afgesloten in 2022); Microscopic evaluation of clots in ECMO systems, Octapharma, rol als PI; IPTN ThromPED registry (international observational registry/study of children with thrombosis, financier BI, BMS en INVENT, rol als chair IPTN	Geen	Adviseur voor verschillende farmaceuten voor ontwikkeling van onderzoek van antistollingsmiddelen of antidota bij kinderen zoals Asundexian (Bayer BV), andexanet (Astra Zeneca)	Geen restricties (onderwerp van commercieel gefinancierd onderzoek valt buiten bestek van deze cyclus, adviesrollen neergelegd gedurende de richtlijnontwikkeling.)
*Krug*	Chirurg, LUMC	Geen	Geen	Geen	Geen	Geen	Geen	Geen restricties
*de Munnik*	Klinisch geneticus Radboudumc Klinisch geneticus MUMC+	Voorzitter commissie kwaliteit VKGN, Lid werkgroep prenatale genetica VKGN, Vertegenwoordiger in de raad van Kwaliteit van de FMS	Geen	Geen	Geen	Geen	Geen	Geen restricties
*Nossent*	Longarts Amsterdam UMC	NVALT Bronkhorst Colloquium(onbetaald); NVALT CCO Pulmonary Vascular Diseases and ILD; chair (betaald); Scientific Committtee PHA Europe (onbetaald); ERS/ESC taskforce redefining pulmonary arterial hypertension with cardiopulmonary comorbidities; secretary (onbetaald); PHAROS TF PH-CLD (onbetaald); Medical advisory board: MSD. (betaald).	Geen.	Geen	E.J. Nossent has received research grants from: Janssen Bayer/MSD Boehringer Ingelheim B.V. (OPTICS-studie, afgerond) United Therapeutics/Ferrer AbbVie Breathomix (P4O2 ILD-extension, rol als projectleider)	Geen	Geen	Geen restricties (studies en betreffen onderwerpen die niet relevant zijn in deze cyclus)
Betrokken clusterexpertisegroepleden
*Klok*	Internist, LUMC Leiden, betaald (1 FTE) Universiteit van Mainz (onbetaald)	voorzitter NVIVG voorzitter Dutch Thrombosis Network aankomend voorzitter ESC werkgroep pulmonale circulatie Diverse richtlijncommissies en werkgroepen van ESC en ERS (onbetaald)	Geen	Geen	• Bayer, Leo Pharma en BSCI (toelichting: Ik heb recent een project voorgezeten om met een internationale werkgroep een standaard set van uitkomsten (ICHOM) te maken voor VTE. Dit project werd financieel ondersteund door Bayer (40k EUR), BSCI (40k EUR) en Leo Pharma (40k EUR). Dit betrof ‘ unrestricted’ grants, waarbij deze sponsoren op geen enkele manier invloed hadden op de inhoud van het projetct, dat in 2020 begon en nu is afgerond), • Actelion en The Netherlands Organisation for Health Research and Development (toelichting: Ik ben mede-aanvrager van 3 ZonMw beurzen voor onderzoek naar voorkomen van VTE en herseninfarcten bij COVID-19 patiënten (DC&TC en CORONIS consortium). De DC&TC wordt ook ondersteund door TSN en een unrestricted grant (75k EUR) van Actelion; dat laatste zodat we extra diagnostiek konden doen tijdens lange termijn follow-up van COVID-19 patiënten die ook een longembolie door hebben gemaakt. Met deze diagnostiek konden we de lange termijn impact van longembolie in deze setting beter vaststellen. Dit project is afgerond.), • The Dutch Thrombosis Association (toelichting: ik doe onderzoek naar nieuwe beeldvormende technieken van trombose met hulp van de TSN), • The Dutch Heart Foundation (toelichting: Daarnaast heb ik dit jaar een project naar lange termijn prognose van longembolie afgerond dat was ondersteund door een dekker beurs van de hartstichting) • The Horizon Europe Program (toelichting: ik ben de voorzitter van een Europees consortium dat wordt gefinancierd vanuit het Horizon Europe programma en tot doel heeft het gebruik van antitrombotische medicatie in de laatste levensfase te optimaliseren. Tevens WP leider in een nader consortium dat onderzoek doet naar samen beslissen over duur antistolling na veneuze trombose ) •ZonMw/ZIN/Hartstichting - studie die onderzoekt wat de rol van katheter trombectomie is bij hoog risico longembolie. 2 catheter bedrijven (Inari en Penumbra) leveren ook een unrestricted grant hiervoor, projectleidersrol	Geen	Geen	Geen restricties (onderwerp van commercieel gefinancierd onderzoek valt buiten bestek van deze cyclus)
*Lauw*	Internist-hematoloog, Erasmus MC Rotterdam, afdeling hematologie	Scientific editor HemaSphere, betaald, EHA Faculty CRTH, betaald Editorial board member van diverse jounrals in hematologi en trombose, onbetaald	nvt	nvt	1. ZONMW- Prevention of venous thromboembolic complications to optimize treatment for ALL (projectleidersrol, betreft studie naar LMWH, afgerond) 2. GlaxoSmithKline- Prevention of venous thromboembolic complications to optimize treatment for ALL (projectleidersrol, afgerond) 3. LeoPharma- Treatment of VTE in hematological malignancies (projectleidersrol, betreft restricted grant voor literatuuronderzoek naar alle antistollingsmiddelen) 4. ISTH, Splanchnic Venous Thrombosis Outcomes in Patients with Myeloproliferative Neoplasms (SSC grant, projectleidersrol) 5. INVENT-VTE, ADAPTiON-study, Apixaban Dose Adjustment in Patient with Thrombocytopenia in Oncology, rol als projectleider	Nvt	Sprekersvergoedingen, betaald aan het Erasmus MC, van: Inari, MEDtalks, Viatris, Amgen, AbbVie	Restrictie t.a.v. besluitvorming over tromboseprofylaxe bij patiënten met ALL en behandeling van VTE bij patiënten met hematologische maligniteiten.

Inbreng patiëntenperspectief

Kwalitatieve raming van mogelijke financiële gevolgen in het kader van de Wkkgz

Bij de richtlijnmodule voerden de clusterleden conform de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) een kwalitatieve raming uit om te beoordelen of de aanbevelingen mogelijk leiden tot substantiële financiële gevolgen. Bij het uitvoeren van deze beoordeling is de richtlijnmodule op verschillende domeinen getoetst (zie het stroomschema bij Werkwijze).

Module	Uitkomst raming	Toelichting
Maligniteit geassocieerde trombose	geen financiële gevolgen	Hoewel uit de toetsing volgt dat de aanbeveling(en) breed toepasbaar zijn (5.000-40.000 patiënten), volgt ook uit de toetsing dat het overgrote deel (±90%) van de zorgaanbieders en zorgverleners al aan de norm voldoet. Er worden daarom geen substantiële financiële gevolgen verwacht.

Werkwijze

Voor meer details over de gebruikte richtlijnmethodologie verwijzen wij u naar de Werkwijze. Relevante informatie voor de ontwikkeling/herziening van deze richtlijnmodule is hieronder weergegeven.

Zoekverantwoording

Zoekstrategie – 17 oktober 2024

Embase.com

*No.*	*Query*	*Results*
#1	'venous thromboembolism'/exp OR 'deep vein thrombosis'/exp OR 'lung embolism'/exp OR (((venous OR vein* OR lung* OR pulmon) NEAR/3 (embol OR microembol* OR thromboembol)):ti,ab,kw) OR vte:ti,ab,kw OR dvt:ti,ab,kw OR ((deep NEAR/3 (thromb* OR 'blood clot' OR embol)):ti,ab,kw)	266601
#2	'neoplasm'/exp OR adenoma:ti,ab,kw OR anticarcinogen:ti,ab,kw OR blastoma:ti,ab,kw OR cancer:ti,ab,kw OR carcinogen:ti,ab,kw OR carcinom:ti,ab,kw OR carcinosarcom:ti,ab,kw OR chordoma:ti,ab,kw OR germinoma:ti,ab,kw OR gonadoblastom:ti,ab,kw OR hepatoblastom:ti,ab,kw OR ((hodgkin NEXT/1 disease):ti,ab,kw) OR leukemi:ti,ab,kw OR lymphangioma:ti,ab,kw OR lymphangiomyoma:ti,ab,kw OR lymphangiosarcom:ti,ab,kw OR lymphom:ti,ab,kw OR malign:ti,ab,kw OR melanom:ti,ab,kw OR meningiom:ti,ab,kw OR mesenchymom:ti,ab,kw OR mesonephrom:ti,ab,kw OR metasta:ti,ab,kw OR neoplas:ti,ab,kw OR neuroma:ti,ab,kw OR nsclc:ti,ab,kw OR oncogen:ti,ab,kw OR oncolog:ti,ab,kw OR paraneoplastic:ti,ab,kw OR plasmacytom:ti,ab,kw OR precancer:ti,ab,kw OR sarcoma:ti,ab,kw OR teratocarcinom:ti,ab,kw OR teratom:ti,ab,kw OR tumor:ti,ab,kw OR tumour:ti,ab,kw	7825666
#3	'thrombosis prevention'/exp OR 'anticoagulant agent'/exp OR 'anticoagulation'/exp OR 'anticoagulant therapy'/exp OR 'apixaban'/exp OR 'dabigatran'/exp OR 'rivaroxaban'/exp OR 'edoxaban'/exp OR 'blood clotting factor 10a inhibitor'/exp OR thromboprophyla:ti,ab,kw OR (((thrombo OR antithrombo* OR vte) NEAR/3 (prophylaxis OR prophylactic OR prevention)):ti,ab,kw) OR 'anti coagulant':ti,ab,kw OR 'anticoagulant':ti,ab,kw OR 'anticoagulat':ti,ab,kw OR 'anti coagulat':ti,ab,kw OR 'antithrombotic':ti,ab,kw OR 'anti thrombotic':ti,ab,kw OR 'antithrombos':ti,ab,kw OR 'anti thrombos':ti,ab,kw OR 'antithrombocytic':ti,ab,kw OR 'anti thrombocytic':ti,ab,kw OR 'antiplatelet agent':ti,ab,kw OR 'antiplatelet drug':ti,ab,kw OR 'platelet aggregation inhibitor':ti,ab,kw OR 'platelet inhibitor':ti,ab,kw OR 'platelet antagonist':ti,ab,kw OR 'thrombocyte aggregation inhibiting agent':ti,ab,kw OR 'thrombocyte aggregation inhibitor':ti,ab,kw OR 'direct oral anticoagulant agent'/exp OR 'direct oral anticoagulant'/exp OR doac:ti,ab,kw OR oac:ti,ab,kw OR oacs:ti,ab,kw OR 'aboxoma':ti,ab,kw OR 'apixaban':ti,ab,kw OR 'apixaben':ti,ab,kw OR 'bms 562247':ti,ab,kw OR 'bms 562247 01':ti,ab,kw OR 'bms562247':ti,ab,kw OR 'eliques':ti,ab,kw OR 'eliquis':ti,ab,kw OR 'lunast':ti,ab,kw OR 'pf 0465257':ti,ab,kw OR 'pf0465257':ti,ab,kw OR 'tah 3311':ti,ab,kw OR 'tah 3341':ti,ab,kw OR 'tah3311':ti,ab,kw OR 'tah3341':ti,ab,kw OR 'bibr 953':ti,ab,kw OR 'bibr953':ti,ab,kw OR 'dabigatran':ti,ab,kw OR 'aban':ti,ab,kw OR 'assubex':ti,ab,kw OR 'ast 8294':ti,ab,kw OR 'ast8294':ti,ab,kw OR 'bay 59 7939':ti,ab,kw OR 'bay 597939':ti,ab,kw OR 'bay59 7939':ti,ab,kw OR 'bay597939':ti,ab,kw OR 'bs 112':ti,ab,kw OR 'bs112':ti,ab,kw OR 'dst 8294':ti,ab,kw OR 'dst8294':ti,ab,kw OR 'jnj 39039039':ti,ab,kw OR 'jnj39039039':ti,ab,kw OR 'kriva':ti,ab,kw OR 'naxat':ti,ab,kw OR 'rivaro':ti,ab,kw OR 'rivarolto':ti,ab,kw OR 'rivaroxaban':ti,ab,kw OR 'rivaxa':ti,ab,kw OR 'throsaben':ti,ab,kw OR 'xanirva':ti,ab,kw OR 'xarelto':ti,ab,kw OR 'xerdoxo':ti,ab,kw OR 'xindus':ti,ab,kw OR 'du 176':ti,ab,kw OR 'du 176b':ti,ab,kw OR 'du176':ti,ab,kw OR 'du176b':ti,ab,kw OR 'edoxaban':ti,ab,kw OR 'edoxaban tosilate':ti,ab,kw OR 'edoxaban tosylate':ti,ab,kw OR 'endoxaban':ti,ab,kw OR 'lixiana':ti,ab,kw OR 'roteas':ti,ab,kw OR 'savaysa':ti,ab,kw OR ((('factor 10a' OR 'factor xa') NEAR/3 'inhibit*'):ti,ab,kw)	959177
#4	#1 AND #2 AND #3	26130
#5	#4 AND [2018-2025]/py NOT ('conference abstract'/it OR 'editorial'/it OR 'letter'/it OR 'note'/it) NOT (('animal'/exp OR 'animal experiment'/exp OR 'animal model'/exp OR 'nonhuman'/exp) NOT 'human'/exp)	7013
#6	'meta analysis'/exp OR 'meta analysis (topic)'/exp OR metaanaly:ti,ab OR 'meta analy':ti,ab OR metanaly:ti,ab OR 'systematic review'/de OR 'cochrane database of systematic reviews'/jt OR prisma:ti,ab OR prospero:ti,ab OR (((systemati OR scoping OR umbrella OR 'structured literature') NEAR/3 (review* OR overview)):ti,ab) OR ((systemic NEAR/1 review):ti,ab) OR (((systemati OR literature OR database* OR 'data base') NEAR/10 search):ti,ab) OR (((structured OR comprehensive* OR systemic) NEAR/3 search):ti,ab) OR (((literature NEAR/3 review):ti,ab) AND (search:ti,ab OR database:ti,ab OR 'data base':ti,ab)) OR (('data extraction':ti,ab OR 'data source':ti,ab) AND 'study selection':ti,ab) OR ('search strategy':ti,ab AND 'selection criteria':ti,ab) OR ('data source':ti,ab AND 'data synthesis':ti,ab) OR medline:ab OR pubmed:ab OR embase:ab OR cochrane:ab OR (((critical OR rapid) NEAR/2 (review* OR overview* OR synthes)):ti) OR ((((critical OR rapid) NEAR/3 (review OR overview* OR synthes)):ab) AND (search:ab OR database:ab OR 'data base':ab)) OR metasynthes:ti,ab OR 'meta synthes':ti,ab	1070871
#7	'randomized controlled trial'/exp OR random:ti,ab OR (((pragmatic OR practical) NEAR/1 'clinical trial'):ti,ab) OR ((('non inferiority' OR noninferiority OR superiority OR equivalence) NEAR/3 trial*):ti,ab) OR rct:ti,ab,kw	2257783
#8	#5 AND #6 - SR	646
#9	#5 AND #7 NOT #8 - RCT	505
#10	#8 OR #9 - Totaal	1151

Ovid/Medline

#	*Searches*	*Results*
1	Venous Thromboembolism/ or exp Venous Thrombosis/ or exp Pulmonary Embolism/ or ((venous or vein* or lung* or pulmon) adj3 (embol or microembol* or thromboembol)).ti,ab,kf. or vte.ti,ab,kf. or dvt.ti,ab,kf. or (deep adj3 (thromb or 'blood clot' or embol)).ti,ab,kf.	159254
2	exp Neoplasms/ or adenoma.ti,ab,kf. or anticarcinogen.ti,ab,kf. or blastoma.ti,ab,kf. or cancer.ti,ab,kf. or carcinogen.ti,ab,kf. or carcinom.ti,ab,kf. or carcinosarcoma.ti,ab,kf. or chordoma.ti,ab,kf. or germinoma.ti,ab,kf. or gonadoblastom.ti,ab,kf. or hepatoblastom.ti,ab,kf. or (hodgkin adj1 disease).ti,ab,kf. or leukemi.ti,ab,kf. or lymphangioma.ti,ab,kf. or lymphangiomyoma.ti,ab,kf. or lymphangiosarcom.ti,ab,kf. or lymphom.ti,ab,kf. or malign.ti,ab,kf. or melanom.ti,ab,kf. or meningiom.ti,ab,kf. or mesenchymom.ti,ab,kf. or mesonephrom.ti,ab,kf. or metasta.ti,ab,kf. or neoplas.ti,ab,kf. or neuroma.ti,ab,kf. or nsclc.ti,ab,kf. or oncogen.ti,ab,kf. or oncolog.ti,ab,kf. or paraneoplastic.ti,ab,kf. or plasmacytom.ti,ab,kf. or precancer.ti,ab,kf. or sarcoma.ti,ab,kf. or teratocarcinom.ti,ab,kf. or teratom.ti,ab,kf. or tumor.ti,ab,kf. or tumour.ti,ab,kf.	5600681
3	exp Anticoagulants/ or exp Platelet Aggregation Inhibitors/ or exp Dabigatran/ or exp Rivaroxaban/ or exp Factor Xa Inhibitors/ or thromboprophyla.ti,ab,kf. or ((thrombo or antithrombo* or vte) adj3 (prophylaxis or prophylactic or prevention)).ti,ab,kf. or (anti coagulant* or anticoagulant* or anticoagulat* or anti coagulat* or antithrombotic* or anti thrombotic* or 'antithrombos' or 'anti thrombos' or antithrombocytic* or anti thrombocytic* or 'antiplatelet agent' or 'antiplatelet drug' or 'platelet aggregation inhibitor' or 'platelet inhibitor' or platelet antagonist* or 'thrombocyte aggregation inhibiting agent' or 'thrombocyte aggregation inhibitor' or doac).ti,ab,kf. or oac.ti,ab,kf. or oacs.ti,ab,kf. or aboxoma.ti,ab,kf. or apixaban.ti,ab,kf. or apixaben.ti,ab,kf. or bms 562247.ti,ab,kf. or "bms 562247 01".ti,ab,kf. or bms562247.ti,ab,kf. or eliques.ti,ab,kf. or eliquis.ti,ab,kf. or lunast.ti,ab,kf. or "pf 0465257".ti,ab,kf. or pf0465257.ti,ab,kf. or tah 3311.ti,ab,kf. or tah 3341.ti,ab,kf. or tah3311.ti,ab,kf. or tah3341.ti,ab,kf. or bibr 953.ti,ab,kf. or bibr953.ti,ab,kf. or dabigatran.ti,ab,kf. or aban.ti,ab,kf. or assubex.ti,ab,kf. or ast 8294.ti,ab,kf. or ast8294.ti,ab,kf. or bay 59 7939.ti,ab,kf. or bay 597939.ti,ab,kf. or bay59 7939.ti,ab,kf. or bay597939.ti,ab,kf. or bs 112.ti,ab,kf. or bs112.ti,ab,kf. or dst 8294.ti,ab,kf. or dst8294.ti,ab,kf. or jnj 39039039.ti,ab,kf. or jnj39039039.ti,ab,kf. or kriva.ti,ab,kf. or naxat.ti,ab,kf. or rivaro.ti,ab,kf. or rivarolto.ti,ab,kf. or rivaroxaban.ti,ab,kf. or rivaxa.ti,ab,kf. or throsaben.ti,ab,kf. or xanirva.ti,ab,kf. or xarelto.ti,ab,kf. or xerdoxo.ti,ab,kf. or xindus.ti,ab,kf. or du 176.ti,ab,kf. or du 176b.ti,ab,kf. or du176.ti,ab,kf. or du176b.ti,ab,kf. or edoxaban.ti,ab,kf. or edoxaban tosilate.ti,ab,kf. or edoxaban tosylate.ti,ab,kf. or endoxaban.ti,ab,kf. or lixiana.ti,ab,kf. or roteas.ti,ab,kf. or savaysa.ti,ab,kf. or ((factor 10a or factor xa) adj3 inhibit).ti,ab,kf.	455799
4	1 and 2 and 3	8718
5	limit 4 to yr="2018 -Current"	3568
6	5 not (comment/ or editorial/ or letter/) not ((exp animals/ or exp models, animal/) not humans/)	3399
7	meta-analysis/ or meta-analysis as topic/ or (metaanaly* or meta-analy* or metanaly).ti,ab,kf. or systematic review/ or cochrane.jw. or (prisma or prospero).ti,ab,kf. or ((systemati or scoping or umbrella or "structured literature") adj3 (review* or overview)).ti,ab,kf. or (systemic adj1 review).ti,ab,kf. or ((systemati or literature or database* or data-base) adj10 search).ti,ab,kf. or ((structured or comprehensive* or systemic) adj3 search).ti,ab,kf. or ((literature adj3 review) and (search or database* or data-base)).ti,ab,kf. or (("data extraction" or "data source") and "study selection").ti,ab,kf. or ("search strategy" and "selection criteria").ti,ab,kf. or ("data source" and "data synthesis").ti,ab,kf. or (medline or pubmed or embase or cochrane).ab. or ((critical or rapid) adj2 (review or overview* or synthes)).ti. or (((critical or rapid) adj3 (review or overview* or synthes)) and (search or database* or data-base)).ab. or (metasynthes or meta-synthes*).ti,ab,kf.	782315
8	exp randomized controlled trial/ or randomized controlled trials as topic/ or random.ti,ab. or rct?.ti,ab. or ((pragmatic or practical) adj "clinical trial").ti,ab,kf. or ((non-inferiority or noninferiority or superiority or equivalence) adj3 trial*).ti,ab,kf.	1762443
9	6 and 7 - SR	403
10	(6 and 8) not 9 - RCT	333
11	9 or 10 - Totaal	736

23 april 2018

Medline (PubMed) 23 april 2018

(("direct oral anticoagulants"(tw) OR "direct oral anticoagulant"(tw) OR "DOAC"(tw) OR "DOACs"(tw) OR "rivaroxaban"(tw) OR "rivaroxaban"(Supplementary Concept) OR "Xarelto"(tw) OR "BAY 59-7939"(tw) OR "dabigatran"(tw) OR "dabigatran"(Supplementary Concept) OR "apixaban"(tw) OR "apixaban" (Supplementary Concept) OR "BMS 562247"(tw) OR "BMS-562247"(tw) OR "edoxaban"(Supplementary Concept) OR "Edoxaban"(tw) OR "DU-176b"(tw) OR "DU-176"(tw) OR "direct thrombin inhibitor"(tw) OR "direct thrombin inhibitors"(tw) OR "betrixaban"(Supplementary Concept) OR "Betrixaban"(tw) OR "melagatran"(Supplementary Concept) OR "Melagatran"(tw) OR "ximelagatran"(Supplementary Concept) OR "ximelagatran"(tw) OR "xi-melagatran"(tw) OR "Exanta"(tw) OR "H 376 95"(tw) OR "H 376-95"(tw) OR noac*(tw) OR "novel oral anticoagulant"(tw) OR "novel oral anticoagulants"(tw) OR "new oral anticoagulant"(tw) OR "new oral anticoagulants"(tw) OR "New orally active anticoagulants"(tw) OR "New oral anticoagulant"(tw) OR "New oral anticoagulants"(tw) OR "NOAC"(tw) OR "NOACs"(tw)) AND ("Venous Thrombosis"(mesh) OR "Venous Thrombosis"(tw) OR "Phlebothrombosis"(tw) OR "Vein Thrombosis"(tw) OR "Venous Thromboembolism"(mesh) OR "Venous Thromboembolism"(tw) OR "DVT"(tw) OR "Pulmonary Embolism"(mesh) OR "pulmonary embolism"(tw) OR "Pulmonary Thromboembolism"(tw) OR "lung embolism"(tw) OR "lung thromboembolism"(tw)) AND ("Neoplasms"(Mesh) OR "cancer"(tw) OR "cancers"(tw) OR "neoplasm"(tw) OR "neoplasms"(tw) OR "tumor"(tw) OR "tumors"(tw) OR "tumour"(tw) OR "tumours"(tw) OR "carcinoma"(tw) OR "carcinomas"(tw) OR "malignancy"(tw) OR "malignancies"(tw)))

Aantal hits: 350

(Ref ID 1-310)

Embase (Ovid) 23 april 2018

(("direct oral anticoagulants".ti,ab OR "direct oral anticoagulant".ti,ab OR "DOAC".ti,ab OR "DOACs".ti,ab OR *"rivaroxaban"/ OR *"dabigatran"/ OR *"dabigatran etexilate"/ OR *"apixaban"/ OR *"edoxaban"/ OR exp *"blood clotting factor 10a inhibitor"/ OR "rivaroxaban".ti,ab OR "Xarelto".ti,ab OR "BAY 59-7939".ti,ab OR "dabigatran".ti,ab OR "apixaban".ti,ab OR "BMS 562247".ti,ab OR "BMS-562247".ti,ab OR "Edoxaban".ti,ab OR "DU-176b".ti,ab OR "DU-176".ti,ab OR "direct thrombin inhibitor".ti,ab OR "direct thrombin inhibitors".ti,ab OR *"betrixaban"/ OR "Betrixaban".ti,ab OR *"melagatran"/ OR "Melagatran".ti,ab OR *"ximelagatran"/ OR "ximelagatran".ti,ab OR "xi-melagatran".ti,ab OR "Exanta".ti,ab OR "H 376 95".ti,ab OR "H 376-95".ti,ab OR noac*.ti,ab OR "novel oral anticoagulant".ti,ab OR "novel oral anticoagulants".ti,ab OR "new oral anticoagulant".ti,ab OR "new oral anticoagulants".ti,ab OR "New orally active anticoagulants".ti,ab OR "New oral anticoagulant".ti,ab OR "New oral anticoagulants".ti,ab OR "NOAC".ti,ab OR "NOACs".ti,ab) AND (exp *"Vein Thrombosis"/ OR "Venous Thrombosis".ti,ab OR "Phlebothrombosis".ti,ab OR "Vein Thrombosis".ti,ab OR exp *"Venous Thromboembolism"/ OR "Venous Thromboembolism".ti,ab OR "DVT".ti,ab OR *"Lung Embolism"/ OR "pulmonary embolism".ti,ab OR "Pulmonary Thromboembolism".ti,ab OR "lung embolism".ti,ab OR "lung thromboembolism".ti,ab) AND (exp *"Neoplasms"/ OR "cancer".ti,ab OR "cancers".ti,ab OR "neoplasm".ti,ab OR "neoplasms".ti,ab OR "tumor".ti,ab OR "tumors".ti,ab OR "tumour".ti,ab OR "tumours".ti,ab OR "carcinoma".ti,ab OR "carcinomas".ti,ab OR "malignancy".ti,ab OR "malignancies".ti,ab)) NOT (conference review or conference abstract).pt

Aantal hits: 361, waarvan 93 uniek (Ref ID 351-456)

Web of Science 23 april 2018

(TI=("direct oral anticoagulants" OR "direct oral anticoagulant" OR "DOAC" OR "DOACs" OR "rivaroxaban" OR "dabigatran" OR "dabigatran etexilate" OR "apixaban" OR "edoxaban" OR "blood clotting factor 10a inhibitor" OR "rivaroxaban" OR "Xarelto" OR "BAY 59-7939" OR "dabigatran" OR "apixaban" OR "BMS 562247" OR "BMS-562247" OR "Edoxaban" OR "DU-176b" OR "DU-176" OR "direct thrombin inhibitor" OR "direct thrombin inhibitors" OR "betrixaban" OR "Betrixaban" OR "melagatran" OR "Melagatran" OR "ximelagatran" OR "ximelagatran" OR "xi-melagatran" OR "Exanta" OR "H 376 95" OR "H 376-95" OR noac* OR "novel oral anticoagulant" OR "novel oral anticoagulants" OR "new oral anticoagulant" OR "new oral anticoagulants" OR "New orally active anticoagulants" OR "New oral anticoagulant" OR "New oral anticoagulants" OR "NOAC" OR "NOACs") AND TS=("Vein Thrombosis" OR "Venous Thrombosis" OR "Phlebothrombosis" OR "Vein Thrombosis" OR "Venous Thromboembolism" OR "Venous Thromboembolism" OR "DVT" OR "Lung Embolism" OR "pulmonary embolism" OR "Pulmonary Thromboembolism" OR "lung embolism" OR "lung thromboembolism") AND TS=("Neoplasms" OR "cancer" OR "cancers" OR "neoplasm" OR "neoplasms" OR "tumor" OR "tumors" OR "tumour" OR "tumours" OR "carcinoma" OR "carcinomas" OR "malignancy" OR "malignancies")) OR (TS=("direct oral anticoagulants" OR "direct oral anticoagulant" OR "DOAC" OR "DOACs" OR "rivaroxaban" OR "dabigatran" OR "dabigatran etexilate" OR "apixaban" OR "edoxaban" OR "blood clotting factor 10a inhibitor" OR "rivaroxaban" OR "Xarelto" OR "BAY 59-7939" OR "dabigatran" OR "apixaban" OR "BMS 562247" OR "BMS-562247" OR "Edoxaban" OR "DU-176b" OR "DU-176" OR "direct thrombin inhibitor" OR "direct thrombin inhibitors" OR "betrixaban" OR "Betrixaban" OR "melagatran" OR "Melagatran" OR "ximelagatran" OR "ximelagatran" OR "xi-melagatran" OR "Exanta" OR "H 376 95" OR "H 376-95" OR noac* OR "novel oral anticoagulant" OR "novel oral anticoagulants" OR "new oral anticoagulant" OR "new oral anticoagulants" OR "New orally active anticoagulants" OR "New oral anticoagulant" OR "New oral anticoagulants" OR "NOAC" OR "NOACs") AND TI=("Vein Thrombosis" OR "Venous Thrombosis" OR "Phlebothrombosis" OR "Vein Thrombosis" OR "Venous Thromboembolism" OR "Venous Thromboembolism" OR "DVT" OR "Lung Embolism" OR "pulmonary embolism" OR "Pulmonary Thromboembolism" OR "lung embolism" OR "lung thromboembolism") AND TS=("Neoplasms" OR "cancer" OR "cancers" OR "neoplasm" OR "neoplasms" OR "tumor" OR "tumors" OR "tumour" OR "tumours" OR "carcinoma" OR "carcinomas" OR "malignancy" OR "malignancies")) OR (TS=("direct oral anticoagulants" OR "direct oral anticoagulant" OR "DOAC" OR "DOACs" OR "rivaroxaban" OR "dabigatran" OR "dabigatran etexilate" OR "apixaban" OR "edoxaban" OR "blood clotting factor 10a inhibitor" OR "rivaroxaban" OR "Xarelto" OR "BAY 59-7939" OR "dabigatran" OR "apixaban" OR "BMS 562247" OR "BMS-562247" OR "Edoxaban" OR "DU-176b" OR "DU-176" OR "direct thrombin inhibitor" OR "direct thrombin inhibitors" OR "betrixaban" OR "Betrixaban" OR "melagatran" OR "Melagatran" OR "ximelagatran" OR "ximelagatran" OR "xi-melagatran" OR "Exanta" OR "H 376 95" OR "H 376-95" OR noac* OR "novel oral anticoagulant" OR "novel oral anticoagulants" OR "new oral anticoagulant" OR "new oral anticoagulants" OR "New orally active anticoagulants" OR "New oral anticoagulant" OR "New oral anticoagulants" OR "NOAC" OR "NOACs") AND TS=("Vein Thrombosis" OR "Venous Thrombosis" OR "Phlebothrombosis" OR "Vein Thrombosis" OR "Venous Thromboembolism" OR "Venous Thromboembolism" OR "DVT" OR "Lung Embolism" OR "pulmonary embolism" OR "Pulmonary Thromboembolism" OR "lung embolism" OR "lung thromboembolism") AND TI=("Neoplasms" OR "cancer" OR "cancers" OR "neoplasm" OR "neoplasms" OR "tumor" OR "tumors" OR "tumour" OR "tumours" OR "carcinoma" OR "carcinomas" OR "malignancy" OR "malignancies"))

NOT (conference review or conference abstract).pt

NOT ti=(veterinary OR rabbit OR rabbits OR animal OR animals OR mouse OR mice OR rodent OR rodents OR rat OR rats OR pig OR pigs OR porcine OR horse* OR equine OR cow OR cows OR bovine OR goat OR goats OR sheep OR ovine OR canine OR dog OR dogs OR feline OR cat OR cats))

Aantal hits: 302, waarvan 70 uniek (Ref ID 457-529)

Cochrane Library 23 april 2018

(("direct oral anticoagulants" OR "direct oral anticoagulant" OR "DOAC" OR "DOACs" OR "rivaroxaban" OR "dabigatran" OR "dabigatran etexilate" OR "apixaban" OR "edoxaban" OR "blood clotting factor 10a inhibitor" OR "rivaroxaban" OR "Xarelto" OR "BAY 59-7939" OR "dabigatran" OR "apixaban" OR "BMS 562247" OR "BMS-562247" OR "Edoxaban" OR "DU-176b" OR "DU-176" OR "direct thrombin inhibitor" OR "direct thrombin inhibitors" OR "betrixaban" OR "Betrixaban" OR "melagatran" OR "Melagatran" OR "ximelagatran" OR "ximelagatran" OR "xi-melagatran" OR "Exanta" OR "H 376 95" OR "H 376-95" OR noac* OR "novel oral anticoagulant" OR "novel oral anticoagulants" OR "new oral anticoagulant" OR "new oral anticoagulants" OR "New orally active anticoagulants" OR "New oral anticoagulant" OR "New oral anticoagulants" OR "NOAC" OR "NOACs") AND ("Vein Thrombosis" OR "Venous Thrombosis" OR "Phlebothrombosis" OR "Vein Thrombosis" OR "Venous Thromboembolism" OR "Venous Thromboembolism" OR "DVT" OR "Lung Embolism" OR "pulmonary embolism" OR "Pulmonary Thromboembolism" OR "lung embolism" OR "lung thromboembolism") AND ("Neoplasms" OR "cancer" OR "cancers" OR "neoplasm" OR "neoplasms" OR "tumor" OR "tumors" OR "tumour" OR "tumours" OR "carcinoma" OR "carcinomas" OR "malignancy" OR "malignancies")):ti,ab,kw

Aantal hits: 63, waarvan 18 uniek (Ref ID 530-550)

Academic Search Premier 23 april 2018

TI(("direct oral anticoagulants" OR "direct oral anticoagulant" OR "DOAC" OR "DOACs" OR "rivaroxaban" OR "dabigatran" OR "dabigatran etexilate" OR "apixaban" OR "edoxaban" OR "blood clotting factor 10a inhibitor" OR "rivaroxaban" OR "Xarelto" OR "BAY 59-7939" OR "dabigatran" OR "apixaban" OR "BMS 562247" OR "BMS-562247" OR "Edoxaban" OR "DU-176b" OR "DU-176" OR "direct thrombin inhibitor" OR "direct thrombin inhibitors" OR "betrixaban" OR "Betrixaban" OR "melagatran" OR "Melagatran" OR "ximelagatran" OR "ximelagatran" OR "xi-melagatran" OR "Exanta" OR "H 376 95" OR "H 376-95" OR noac* OR "novel oral anticoagulant" OR "novel oral anticoagulants" OR "new oral anticoagulant" OR "new oral anticoagulants" OR "New orally active anticoagulants" OR "New oral anticoagulant" OR "New oral anticoagulants" OR "NOAC" OR "NOACs") AND ("Vein Thrombosis" OR "Venous Thrombosis" OR "Phlebothrombosis" OR "Vein Thrombosis" OR "Venous Thromboembolism" OR "Venous Thromboembolism" OR "DVT" OR "Lung Embolism" OR "pulmonary embolism" OR "Pulmonary Thromboembolism" OR "lung embolism" OR "lung thromboembolism") AND ("Neoplasms" OR "cancer" OR "cancers" OR "neoplasm" OR "neoplasms" OR "tumor" OR "tumors" OR "tumour" OR "tumours" OR "carcinoma" OR "carcinomas" OR "malignancy" OR "malignancies")) OR SU(("direct oral anticoagulants" OR "direct oral anticoagulant" OR "DOAC" OR "DOACs" OR "rivaroxaban" OR "dabigatran" OR "dabigatran etexilate" OR "apixaban" OR "edoxaban" OR "blood clotting factor 10a inhibitor" OR "rivaroxaban" OR "Xarelto" OR "BAY 59-7939" OR "dabigatran" OR "apixaban" OR "BMS 562247" OR "BMS-562247" OR "Edoxaban" OR "DU-176b" OR "DU-176" OR "direct thrombin inhibitor" OR "direct thrombin inhibitors" OR "betrixaban" OR "Betrixaban" OR "melagatran" OR "Melagatran" OR "ximelagatran" OR "ximelagatran" OR "xi-melagatran" OR "Exanta" OR "H 376 95" OR "H 376-95" OR noac* OR "novel oral anticoagulant" OR "novel oral anticoagulants" OR "new oral anticoagulant" OR "new oral anticoagulants" OR "New orally active anticoagulants" OR "New oral anticoagulant" OR "New oral anticoagulants" OR "NOAC" OR "NOACs") AND ("Vein Thrombosis" OR "Venous Thrombosis" OR "Phlebothrombosis" OR "Vein Thrombosis" OR "Venous Thromboembolism" OR "Venous Thromboembolism" OR "DVT" OR "Lung Embolism" OR "pulmonary embolism" OR "Pulmonary Thromboembolism" OR "lung embolism" OR "lung thromboembolism") AND ("Neoplasms" OR "cancer" OR "cancers" OR "neoplasm" OR "neoplasms" OR "tumor" OR "tumors" OR "tumour" OR "tumours" OR "carcinoma" OR "carcinomas" OR "malignancy" OR "malignancies")) OR KW(("direct oral anticoagulants" OR "direct oral anticoagulant" OR "DOAC" OR "DOACs" OR "rivaroxaban" OR "dabigatran" OR "dabigatran etexilate" OR "apixaban" OR "edoxaban" OR "blood clotting factor 10a inhibitor" OR "rivaroxaban" OR "Xarelto" OR "BAY 59-7939" OR "dabigatran" OR "apixaban" OR "BMS 562247" OR "BMS-562247" OR "Edoxaban" OR "DU-176b" OR "DU-176" OR "direct thrombin inhibitor" OR "direct thrombin inhibitors" OR "betrixaban" OR "Betrixaban" OR "melagatran" OR "Melagatran" OR "ximelagatran" OR "ximelagatran" OR "xi-melagatran" OR "Exanta" OR "H 376 95" OR "H 376-95" OR noac* OR "novel oral anticoagulant" OR "novel oral anticoagulants" OR "new oral anticoagulant" OR "new oral anticoagulants" OR "New orally active anticoagulants" OR "New oral anticoagulant" OR "New oral anticoagulants" OR "NOAC" OR "NOACs") AND ("Vein Thrombosis" OR "Venous Thrombosis" OR "Phlebothrombosis" OR "Vein Thrombosis" OR "Venous Thromboembolism" OR "Venous Thromboembolism" OR "DVT" OR "Lung Embolism" OR "pulmonary embolism" OR "Pulmonary Thromboembolism" OR "lung embolism" OR "lung thromboembolism") AND ("Neoplasms" OR "cancer" OR "cancers" OR "neoplasm" OR "neoplasms" OR "tumor" OR "tumors" OR "tumour" OR "tumours" OR "carcinoma" OR "carcinomas" OR "malignancy" OR "malignancies"))

Aantal hits: 34, waarvan 9 uniek (Ref ID 551-559)

Totaal aantal hits: 540

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