Are there ongoing head-to-head studies between Direct Oral Anticoagulants (DOACs)?

Head-to-Head Studies Between DOACs

No completed head-to-head randomized controlled trials comparing different DOACs exist, and current guidelines do not recommend one DOAC over another based on direct comparative evidence. 1

Current Evidence Landscape

Absence of Direct Comparative Trials

• The American Society of Hematology 2020 guidelines explicitly state: "We did not find any systematic reviews or randomized trials comparing different DOACs head to head" 1
• Subgroup analyses found no interaction between specific DOAC agents and risk of mortality, PE, symptomatic DVT, or major bleeding when compared indirectly against vitamin K antagonists 1
• The certainty in comparative evidence between DOACs was judged "very low" for all relevant outcomes, given only indirect evidence is available 1

Ongoing Research Status

• One research commentary from 2019 explicitly calls for head-to-head DOAC trials, stating "it's time for head-to-head trials with DOACs" due to growing evidence that each DOAC has a specific risk profile 2
• The CARAVAGGIO trial (NCT03045406) comparing apixaban versus dalteparin in cancer patients was recruiting as of 2019, but this compares a DOAC to LMWH, not DOAC-to-DOAC 1
• No specific ongoing DOAC versus DOAC trials are identified in the provided evidence 1

Why Head-to-Head Trials Are Needed

Evidence of Potential Differences

• Indirect comparisons and retrospective cohort studies suggest apixaban may be associated with lower risk of major bleeding than other DOACs, but this cannot be confirmed without direct trials 2
• Network meta-analyses have attempted indirect comparisons, but these are methodologically limited and cannot replace randomized controlled trials 2
• Proper randomization is crucial for unprejudiced treatment allocation and minimization of unmeasured and unknown confounding—something observational studies cannot achieve 2

Current Clinical Decision-Making

• The choice of specific DOAC is currently based on physician and patient preferences, reimbursement, availability, and drug-specific factors rather than comparative efficacy data 1, 2
• Important selection factors include:
  • Renal function: dabigatran ~80% renal clearance versus apixaban 25% renal clearance 1
  • Hepatic function: dabigatran least reliant on hepatic clearance 1
  • Dosing frequency: once-daily versus twice-daily preferences 1
  • Need for food intake with medication 1
  • Requirement for initial parenteral anticoagulation: dabigatran and edoxaban require LMWH lead-in, while rivaroxaban and apixaban do not 1, 3

Clinical Implications

What This Means for Practice

• All DOACs are considered equivalent in the absence of head-to-head data, with selection based on patient-specific factors rather than superior efficacy of one agent 1
• Prospective research studies comparing different DOACs would be particularly valuable in selected populations such as individuals with renal insufficiency, liver disease, or morbid obesity 1
• Until head-to-head trials are completed, clinicians must rely on indirect comparisons, observational data, and patient-specific contraindications to guide DOAC selection 1, 2