Can a patient with a history of pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension who requires anticoagulation for conditions such as atrial fibrillation or deep vein thrombosis be on Adempas (riociguat) and Eliquis (apixaban)?

Concurrent Use of Adempas (Riociguat) and Eliquis (Apixaban)

Yes, a patient can be on both Adempas and Eliquis concurrently, as lifelong anticoagulation is mandatory for all CTEPH patients regardless of riociguat therapy, and emerging evidence supports the use of DOACs including apixaban in this population.

Mandatory Anticoagulation in CTEPH

• All patients with chronic thromboembolic pulmonary hypertension require lifelong anticoagulation, including those treated with riociguat (Adempas), as recommended by the European Heart Society 1, 2
• This anticoagulation requirement persists even after successful pulmonary endarterectomy or balloon pulmonary angioplasty 2
• The American College of Chest Physicians recommends extended (indefinite) anticoagulation in all CTEPH patients 1

Riociguat's Role and Mechanism

• Riociguat is indicated for inoperable CTEPH or persistent/recurrent CTEPH after pulmonary endarterectomy, and works as a soluble guanylate cyclase stimulator to address pulmonary microvascular disease 2
• Riociguat does NOT replace anticoagulation—it is a pulmonary vasodilator that complements mandatory anticoagulation therapy 2
• The drug improves 6-minute walking distance by 39 meters and reduces pulmonary vascular resistance by 246 dyn.cm.s⁻⁵ compared to placebo 2

Evidence Supporting DOACs (Including Apixaban) in CTEPH

• A prospective cohort study of 20 CTEPH patients treated with DOACs (including one patient on apixaban) showed no episodes of venous thromboembolism recurrence over a mean follow-up of 20.9 months, with only one major bleeding event after trauma 3
• The EXPERT study, a large international multicenter prospective cohort, followed 198 CTEPH patients on riociguat who were receiving NOACs (including apixaban), demonstrating similar hemorrhagic event rates compared to warfarin 4
• Exposure-adjusted hemorrhagic event rates were comparable between NOAC and VKA groups in CTEPH patients on riociguat, though embolic/thrombotic event rates were slightly higher in the NOAC group (small absolute numbers) 4

Critical Drug Interaction Considerations

• The major contraindication with riociguat is concurrent use with PDE5 inhibitors (sildenafil, tadalafil, vardenafil), NOT with anticoagulants like apixaban 2
• Riociguat can cause bleeding including pulmonary hemorrhage, so careful monitoring is required when combined with any anticoagulant 5
• Additive bleeding risk exists when riociguat is combined with antithrombotic drugs, but this does not constitute an absolute contraindication—rather, it requires vigilant monitoring 5

Practical Management Algorithm

When initiating or continuing both medications:

• Start riociguat at 1 mg three times daily and titrate by 0.5 mg increments every 2 weeks to maximum 2.5 mg three times daily, based on systolic blood pressure >95 mmHg and absence of hypotensive symptoms 2
• Monitor systolic blood pressure at trough during the 8-week titration period 2
• Assess for signs of bleeding at each follow-up visit, given the additive hemorrhagic risk 5, 4
• Perform WHO functional class assessment and 6-minute walk distance testing to evaluate treatment response 2
• Follow patients at specialized pulmonary hypertension centers with expertise in CTEPH management 2

Common Pitfalls to Avoid

• Do not discontinue anticoagulation when starting riociguat—these medications serve different therapeutic purposes and both are required 1, 2
• Do not use riociguat in patients who are candidates for pulmonary endarterectomy, as surgery remains first-line treatment 2
• Do not combine riociguat with PDE5 inhibitors due to life-threatening hypotension risk 2
• Do not assume warfarin is superior to DOACs in CTEPH—emerging evidence supports DOAC use, though larger studies are needed 3, 6

Nuances in the Evidence

While traditional guidelines emphasized vitamin K antagonists for CTEPH anticoagulation 1, more recent real-world evidence demonstrates that DOACs including apixaban appear safe and effective in this population 3, 4. The EXPERT study showed similar hemorrhagic event rates between NOACs and warfarin in CTEPH patients on riociguat, though slightly higher embolic/thrombotic events were noted with NOACs (small absolute numbers requiring further investigation) 4. Given the established safety profile of apixaban in other thromboembolic conditions and emerging CTEPH-specific data, concurrent use with riociguat is clinically appropriate with proper monitoring 3, 4.