What oral medications, such as Direct Oral Anticoagulants (DOACs) like apixaban (apixaban), rivaroxaban (rivaroxaban), or dabigatran (dabigatran), can be used to prevent Pulmonary Embolism (PE) and Deep Vein Thrombosis (DVT) in patients at risk, particularly those with impaired mobility, a history of clotting disorders, undergoing major surgery, or with a history of cancer?

Oral Medications for Prevention of Pulmonary Embolism and Deep Vein Thrombosis

Direct oral anticoagulants (DOACs)—specifically apixaban, rivaroxaban, edoxaban, or dabigatran—are the preferred oral medications for preventing PE and DVT, with DOACs recommended over vitamin K antagonists for most patients. 1

Primary Prevention in At-Risk Patients

General Population (Non-Cancer)

• For patients with uncomplicated DVT or low-risk PE, DOACs are preferred over vitamin K antagonists (VKAs) for primary treatment and prevention of recurrence. 1
• The American Society of Hematology suggests using DOACs over VKAs based on moderate certainty evidence, though no single DOAC is recommended over another. 1
• Selection among DOACs depends on practical factors: requirement for lead-in parenteral anticoagulation, once versus twice-daily dosing, out-of-pocket cost, renal function, and concomitant medications metabolized through CYP3A4 or P-glycoprotein. 1

Important Exceptions Where DOACs May Not Apply

• Patients with creatinine clearance <30 mL/min should not receive standard DOAC dosing. 1
• Patients with moderate to severe liver disease require alternative anticoagulation strategies. 1
• Patients with antiphospholipid syndrome should avoid DOACs and use alternative anticoagulation. 1

Cancer Patients: Special Considerations

Acute VTE Treatment in Cancer

For patients with active cancer and acute VTE, DOACs (apixaban, rivaroxaban, or edoxaban) are now preferred over low molecular weight heparin (LMWH) for short-term treatment (3-6 months). 1

• The 2023 ASCO guidelines added apixaban as an option for VTE treatment in cancer patients with high quality evidence and a strong recommendation. 1
• DOACs are suggested over LMWH based on low certainty evidence, and over VKAs based on very low certainty evidence. 1
• LMWH remains strongly recommended over unfractionated heparin (UFH) for initial treatment in cancer patients. 1

When to Avoid DOACs in Cancer Patients

Avoid DOACs in cancer patients with:

• Gastrointestinal malignancies with high bleeding risk (particularly gastroesophageal or colorectal cancers with mucosal involvement). 1
• Platelet count <50,000/μL—hold anticoagulation or use reduced-dose LMWH with caution. 1
• Significant drug-drug interactions with chemotherapy agents metabolized through CYP3A4 or P-glycoprotein. 1

In these high-risk scenarios, LMWH (such as dalteparin) remains the safer choice. 1

Primary Thromboprophylaxis in Ambulatory Cancer Patients

For ambulatory cancer patients at high risk (Khorana score ≥2) starting chemotherapy, apixaban 2.5 mg twice daily or rivaroxaban 10 mg once daily can be offered for primary VTE prevention. 1

• The AVERT trial showed apixaban significantly reduced VTE (4.2% vs 10.2%, p<0.001) but increased major bleeding (3.5% vs 1.8%). 1
• The CASSINI trial showed rivaroxaban numerically reduced VTE (6.0% vs 8.8%) with numerically increased major bleeding (2.0% vs 1.0%). 1
• The number needed to treat (NNT) is 17 for apixaban and 35 for rivaroxaban, while the number needed to harm (NNH) for major bleeding is 59 and 101, respectively. 1

This approach is most appropriate for patients with solid tumors or lymphoma at intermediate-to-high VTE risk who do not have gastrointestinal cancer or other high bleeding risk features. 1

Perioperative Prophylaxis After Cancer Surgery

For extended thromboprophylaxis after major cancer surgery, apixaban and rivaroxaban are now acceptable alternatives to LMWH, though with a weak strength of recommendation. 1

• Extended prophylaxis (up to 4 weeks post-discharge) is recommended after major abdominal/pelvic cancer surgery. 1
• LMWH or fondaparinux remain preferred over UFH for perioperative prophylaxis. 1
• Postoperative initiation is preferred over preoperative dosing. 1

Specific DOAC Dosing Regimens

Rivaroxaban

• Treatment of acute DVT/PE: 15 mg twice daily with food for 3 weeks, then 20 mg once daily with food. 2
• Extended prophylaxis after completing initial treatment: 10 mg once daily with food (superior to aspirin 100 mg, HR 0.26, p<0.0001). 2

Apixaban

• Treatment of acute DVT/PE: 10 mg twice daily for 7 days, then 5 mg twice daily. 3
• Primary prophylaxis in high-risk ambulatory cancer patients: 2.5 mg twice daily. 1

Dabigatran and Edoxaban

• Both require initial parenteral anticoagulation (5-10 days) before transitioning to oral therapy. 1, 4
• This requirement makes them less convenient than rivaroxaban or apixaban for acute VTE treatment. 1

Duration of Anticoagulation

For patients with active cancer and VTE, continue anticoagulation for at least 3-6 months, and consider indefinite therapy as long as cancer remains active. 1

• Reassess at 3-6 months based on ongoing VTE risk, bleeding risk, cancer status, and patient preference. 1
• For patients in complete cancer remission, consider discontinuing anticoagulation after 6-12 months. 1
• For patients with idiopathic VTE or persistent risk factors, extended therapy beyond 6 months reduces recurrence risk. 1, 2

Critical Safety Considerations

Bleeding Risk Management

Major bleeding risk is the primary concern with all anticoagulants, occurring in 2-3% of patients annually. 1

• DOACs show consistently lower major bleeding rates than VKAs in non-cancer populations. 1
• In cancer patients, DOACs have similar or slightly lower bleeding rates compared to LMWH. 1
• Avoid concomitant NSAIDs (including topical formulations) with any DOAC, as this increases bleeding risk by at least 60%. 5

Renal Function Monitoring

All DOACs require dose adjustment or avoidance in severe renal impairment (CrCl <30 mL/min). 1

• Monitor renal function at baseline and periodically, especially in elderly patients, those receiving nephrotoxic chemotherapy, or with fluctuating clinical status. 1
• For cancer patients with renal impairment (CrCl 20-50 mL/min), LMWH (particularly tinzaparin) may be safer as it does not accumulate. 6

Drug Interactions

Screen for interactions with CYP3A4 inhibitors/inducers and P-glycoprotein inhibitors before prescribing DOACs. 1

• Strong CYP3A4 and P-glycoprotein inhibitors (e.g., ketoconazole, ritonavir) significantly increase DOAC levels. 1
• Strong inducers (e.g., rifampin, phenytoin, carbamazepine) significantly decrease DOAC efficacy. 1

Common Clinical Pitfalls to Avoid

• Do not use DOACs in patients with mechanical heart valves or moderate-to-severe mitral stenosis—VKAs remain the only option. 1
• Do not abruptly switch from DOAC to warfarin without overlap—this creates a period of inadequate anticoagulation and increased thrombotic risk. 2
• Do not assume "oral" means "safer"—DOACs carry similar overall bleeding risk to warfarin but with different bleeding patterns (less intracranial hemorrhage, potentially more GI bleeding). 1, 4
• Do not forget that incidental PE and subsegmental PE in cancer patients require the same anticoagulation as symptomatic PE. 1