Anticoagulation of cancer patients with non-valvular atrial fibrillation receiving chemotherapy

 

Approximately 4% of cancer patients have non-valvular atrial fibrillation (NVAF) and require anticoagulation for prophylaxis against embolic stroke. One third of these may receive chemotherapy, which will further increase the risk of bleeding and thrombosis. Furthermore, many chemotherapeutic agents interact with commonly used anticoagulants, which may affect their safety and efficacy.

The paucity of data may explain why no guidelines exist to advise on the management of anticoagulation during chemotherapy for patients with NVAF or even which anticoagulant should be used.

The Scientific and Standardization Committee (SSC) for Malignancy and Hemostasis of the International Society for Thrombosis and Hemostasis has reviewed the data around NVAF and cancer in order to produce a guidance document to better inform clinicians 1. Where no data exists, other patient populations or clinical scenarios have been reviewed and used to develop management suggestions.

It is needless to say that vitamin antagonists (VKA) have numerous interactions with chemotherapies or supportive care. The time in therapeutic range of cancer-patients is significantly lower than in non-cancer patients, and cancer-patients on VKA have a 6-fold increase in the risk for major bleeding as compared with non-cancer patients.

Patients with active cancer were excluded from major randomized controlled trials (RCT) evaluating direct oral anticoagulants (DOAC) in NVAF (either directly or indirectly, since life-expectancy was supposed to be greater than 1-2 year to be included in the trials). Nonetheless, secondary analyses of these RCTs were performed on patients with a history of cancer or who developed cancer during follow-up of the trials. It represented around 5% of the included patients and no negative signal was observed with regards to a lower efficacy or safety of DOACs in cancer patients as compared with warfarin.

A retrospective analysis of MarketScan claims in 16,000 patients with cancer and NVAF also showed no negative signal in terms of stroke or major bleeding associated with the use of rivaroxaban or dabigatran as compared with warfarin and perhaps a better safety associated with the use of apixaban 2. However, caution should be made in the interpretation of this study.

Lastly, no evidence was found to support the long-term use of LMWH for stroke prevention in patients with NVAF regardless of the presence or not of cancer. In high-risk patients switching transiently to a LMWH when oral intake is impossible can be considered.

Finally, the SSC proposed the following guidance:

  • SSC recommends individualized anticoagulation regimens after shared decision-making with patients, based wherever possible on risk of stroke, bleeding and patient values.
  • In cancer patients with NVAF already on an anticoagulant regimen before starting chemotherapy, SSC recommends continuing the same anticoagulation regimen unless there are clinically relevant drug-drug interactions.
    1. In cancer patients on chemotherapies with clinically relevant VKA interactions, SSC suggests considering a DOAC if no additional drug-drug interactions with DOAC or close monitoring of VKA (target INR between 2 and 3).
    2. In cancer patients on chemotherapies unable to tolerate an oral route of administration (e.g. nausea and vomiting), SSC suggests the use of parenteral anticoagulation with therapeutic dosing of LMWH with resumption of oral anticoagulation as soon as possible.
  • In cancer patients on chemotherapy with newly diagnosed NVAF, with the exception of patients with luminal gastrointestinal cancers with an intact primary or patients with active gastrointestinal mucosal abnormalities such as duodenal ulcers, gastritis, esophagitis or colitis SSC suggests the use of a DOAC over a VKA or LMWH as anticoagulant therapy if no clinically relevant drug-to-drug interactions are expected.

 

There is a very little evidence to inform the management of anticoagulation for NVAF during chemotherapy. Most guidance suggestions are extrapolated from other populations. An individualised approach to decision making is essential and should take into consideration the aims of chemotherapy and patient preferences and values.

 


References

  1. Delluc A, Wang TF, Yap ES, Ay C, Schaefer J, Carrier M, et al. Anticoagulation of cancer patients with non-valvular atrial fibrillation receiving chemotherapy: Guidance from the SSC of the ISTH. J Thromb Haemost. 2019.
  2. Shah S, Norby FL, Datta YH, Lutsey PL, MacLehose RF, Chen LY, et al. Comparative effectiveness of direct oral anticoagulants and warfarin in patients with cancer and atrial fibrillation. Blood Adv. 2018;2(3):200-9.

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