Play

Play Overview Evidence Contributors

Is the patient already on short-term anticoagulation (e.g., VTE initial treatment)?

NoYes (Patient may NOT be a candidate for Dual Pathway Inhibition (DPI) with rivaroxaban PLUS aspirin at this time.)

According to Bonaca et al. (2020), limb symptoms frequently develop in patients with peripheral artery disease, to include those that are post revascularization. Such symptoms range from severe claudication, which limits function, to critical limb-threatening ischemia. Patients who undergo peripheral revascularization are at high risk for subsequent vascular complications with a risk approximately 4 times as high as that among persons who have never undergone revascularization. Several observations, to include use of inhibiting thrombin-mediated activation of platelets with vorapaxar reduced the risk of acute limb ischemia in patients with stable peripheral artery disease, indicate that the risk of this complication is modifiable. Additionally, the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial showed that rivaroxaban (a selective direct factor Xa inhibitor) at a dose of 2.5 mg twice daily added to aspirin reduced ischemic risk. Additional factors, such as bleeding risk, also plays a role in the judicial use of anticoagulants. Medication treatment plans in the presence of bleeding risk factors will require additional scrutiny as the clinician and patient weigh the risks.

The decision tree used in this app was developed by the Anticoagulation Forum (Barnes, Parikh & Wirth, 2021) as an ACE Rapid Resource, called the Antithrombotic Management Following Peripheral Arterial Disease (PAD) Revascularization. The following disclaimer is posted by the AC Forum, "ACE Rapid Resources are not clinical practice guidelines; they are Anticoagulation Forum, Inc.’s best recommendations based on current knowledge, and no warranty or guaranty is expressed or implied. The content provided is for informational purposes for medical professionals only and is not intended to be used or relied upon by them as specific medical advice, diagnosis, or treatment, the determination of which remains the responsibility of the medical professionals for their patients."

All questions & possible results

Part I: DPI Algorithm in PAD With History of Revascularization or Symptomatic PADTitle not visible

Is the patient already on short-term anticoagulation (e.g., VTE initial treatment)?

Select one option:

No
Yes (Patient may NOT be a candidate for Dual Pathway Inhibition (DPI) with rivaroxaban PLUS aspirin at this time.)

Is the patient already on long-term anticoagulation for AF, mechanical valve, antiphospholipid syndrome (APS), or extended venous thromboembolism (VTE) treatment?

Select one option:

No
Yes (Current use of oral anticoagulants for another condition may be a contraindication for DPI or DAPT in the treatment of PAD)

Is the patient already taking dual antiplatelet therapy for that is required for > 1 month?

*e.g., acute coronary syndrome, recent DES placement inn coronary or below knee arteries

Select one option:

No
Yes (Patient may NOT be a candidate for a change to DPI at this time. Further assessment required.)

Part II: DPI Algorithm in PAD With History of Revascularization or Symptomatic PADTitle not visible

Is CrCl < 15 ml/min?

Select one option:

No
Yes (CrCl <15 ml/min is a contraindication for Rivaroxaban)

Allergy to aspirin?

Select one option:

No
Yes (ASA allergy is a contraindication for DPI or DAPT. Consider clopidogrel monotherapy as an alternative.)

Is the patient already prescribed or using aspirin?

Select one option:

At increased risk of bleeding?

Bleeding Risk Factors to Consider:

Concurrent NSAID or other antiplatelet agents
History of hemorrhagic stroke, intracranial hemorrhage, or significant bleeding
Recent GI ulceration
Active malignant neoplasms at risk of bleeding
History of vascular aneurysms
History of coagulopathies/bleeding disorders
Uncontrolled hypertension (SBP > 160 mmHg)
Heavy alcohol use or esophageal varices
Acute liver or renal failure
Recent trauma or surgery

These factors represent a sampling of bleeding risk factors from validated tools (HAS-BLED, HEMORR2HAGES, IMPROVE-VTE) and the primary literature (VOYAGER-PAD, COMPASS.)

Select one option:

No
Yes (Increased bleed risk may be a contraindication for DPI or DAPT)

Is Rivaroxaban cost or lack of insurance a barrier?

Select one option:

Is the patient already taking other medication that is contraindicated for use with rivaroxaban?

Contraindication Examples

Combined CYP3a and P-gp inducers and inhibitors (ketoconazole, ritonavir, erythromycin, carbamazepine, phenytoin, rifampin, St. John’s wort, etc.) - Xarelto Package Insert. Janssen Pharmaceuticals, 2023.

Select one option:

Possible results

Symptomatic PAD: Consider DPI. If bleed risk, consider aspirin daily only

Treatment Options

If Symptomatic - Dual Pathway Inhibition (DPI):

Rivaroxaban 2.5mg BID -PLUS-
Aspirin 81 mg daily

If Symptomatic & high bleed risk - Monotherapy

Aspirin 81mg daily

For claudication symptoms consider:

Cilostazol 75mg BID: Do NOT use in the presence of heart failure or cardiomyopathy.

Footnote

The rationale behind dual pathway inhibition is to block two different mechanisms for platelet activation to further reduce thrombotic risk. In the COMPASS Trial, the combination of rivaroxaban (a factor Xa inhibitor) and aspirin has been shown to reduce the rates of MACE and MALE (6% vs. 9%, HR 0.69, P < 0.001) versus aspirin monotherapy without increases in fatal or nonfatal bleeding or intracranial hemorrhage.
Major bleeding was increased in DPI vs. ASA (3% vs. 2%, HR 1.61, p=0.008) and was driven by increased gastrointestinal bleeding, and front-loaded in the first year (COMPASS Trial).
For more information, view the Anticoagulation Forum Rapid Resource on PAD and DPI.
Factor Xa inhibitors (rivaroxaban) blocks platelet activation by inhibition of thrombin formation, while aspirin, a COX-1 inhibitor, blocks platelet activation via inhibition of thromboxane A2.

CrCl < 15 ml/min: May NOT be a candidate for Dual Pathway Inhibition (DPI) with Rivaroxaban PLUS aspirin at this time (Symptomatic PAD)

Possible reasons selected that may disqualify DPI as a safe treatment option:

CrCl < 15ml/min
Medication cost or lack of insurance coverage: Consider consult with Pharmacy or Social Work for assistance.
Taking other medication that is contraindicated for use with rivaroxaban

Treatment Options

If Symptomatic - Dual Pathway Inhibition (DPI):

Rivaroxaban 2.5mg BID -PLUS-
Aspirin 81 mg daily

If Symptomatic & high bleed risk - Monotherapy

Aspirin 81mg daily

For claudication symptoms consider:

Cilostazol 75mg BID: Do NOT use in the presence of heart failure or cardiomyopathy.

Footnote

The rationale behind dual pathway inhibition is to block two different mechanisms for platelet activation to further reduce thrombotic risk. In the COMPASS Trial, the combination of rivaroxaban (a factor Xa inhibitor) and aspirin has been shown to reduce the rates of MACE and MALE (6% vs. 9%, HR 0.69, P < 0.001) versus aspirin monotherapy without increases in fatal or nonfatal bleeding or intracranial hemorrhage.
Major bleeding was increased in DPI vs. ASA (3% vs. 2%, HR 1.61, p=0.008) and was driven by increased gastrointestinal bleeding, and front-loaded in the first year (COMPASS Trial).
For more information, view the Anticoagulation Forum Rapid Resource on PAD and DPI.
Factor Xa inhibitors (rivaroxaban) blocks platelet activation by inhibition of thrombin formation, while aspirin, a COX-1 inhibitor, blocks platelet activation via inhibition of thromboxane A2.

Symptomatic PAD & Bleed Risk! Consider aspirin daily as monotherapy. May NOT be a candidate for DPI as this time.

Treatment Options

If Symptomatic - Dual Pathway Inhibition (DPI):

Rivaroxaban 2.5mg BID -PLUS-
Aspirin 81 mg daily

If Symptomatic & high bleed risk - Monotherapy

Aspirin 81mg daily

For claudication symptoms consider:

Cilostazol 75mg BID: Do NOT use in the presence of heart failure or cardiomyopathy.

Footnote

The rationale behind dual pathway inhibition is to block two different mechanisms for platelet activation to further reduce thrombotic risk. In the COMPASS Trial, the combination of rivaroxaban (a factor Xa inhibitor) and aspirin has been shown to reduce the rates of MACE and MALE (6% vs. 9%, HR 0.69, P < 0.001) versus aspirin monotherapy without increases in fatal or nonfatal bleeding or intracranial hemorrhage.
Major bleeding was increased in DPI vs. ASA (3% vs. 2%, HR 1.61, p=0.008) and was driven by increased gastrointestinal bleeding, and front-loaded in the first year (COMPASS Trial).
For more information, view the Anticoagulation Forum Rapid Resource on PAD and DPI.
Factor Xa inhibitors (rivaroxaban) blocks platelet activation by inhibition of thrombin formation, while aspirin, a COX-1 inhibitor, blocks platelet activation via inhibition of thromboxane A2.

If already taking aspirin, confirm the appropriate dosage of aspirin

Medication cost or contraindication: May NOT be a candidate for Dual Pathway Inhibition (DPI) with Rivaroxaban PLUS aspirin at this time (Symptomatic PAD)

Possible reasons selected that may disqualify DPI as a safe treatment option:

CrCl < 15ml/min
Medication cost or lack of insurance coverage: Consider consult with Pharmacy or Social Work for assistance.
Taking other medication that is contraindicated for use with rivaroxaban

Treatment Options

If Symptomatic - Dual Pathway Inhibition (DPI):

Rivaroxaban 2.5mg BID -PLUS-
Aspirin 81 mg daily

If Symptomatic & high bleed risk - Monotherapy

Aspirin 81mg daily

For claudication symptoms consider:

Cilostazol 75mg BID: Do NOT use in the presence of heart failure or cardiomyopathy.

Footnote

The rationale behind dual pathway inhibition is to block two different mechanisms for platelet activation to further reduce thrombotic risk. In the COMPASS Trial, the combination of rivaroxaban (a factor Xa inhibitor) and aspirin has been shown to reduce the rates of MACE and MALE (6% vs. 9%, HR 0.69, P < 0.001) versus aspirin monotherapy without increases in fatal or nonfatal bleeding or intracranial hemorrhage.
Major bleeding was increased in DPI vs. ASA (3% vs. 2%, HR 1.61, p=0.008) and was driven by increased gastrointestinal bleeding, and front-loaded in the first year (COMPASS Trial).
For more information, view the Anticoagulation Forum Rapid Resource on PAD and DPI.
Factor Xa inhibitors (rivaroxaban) blocks platelet activation by inhibition of thrombin formation, while aspirin, a COX-1 inhibitor, blocks platelet activation via inhibition of thromboxane A2.

Warning - Aspirin Allergy: Consider clopidogrel 75mg PO Daily

Symptomatic PAD Plus Other Indication for Short-term Anticoagulation: Continue current antithrombotic therapy as prescribed. Revisit Dual Pathway Inhibition (DPI) - Reconsider in 1-6 months

For claudication symptoms consider:

Cilostazol 75mg BID: Do NOT use in the presence of heart failure or cardiomyopathy.

Symptomatic PAD Plus Other Indication for Anticoagulation: Continue Dual Antiplatelet Therapy (DAPT) with P2Y12 inhibitor (e.g., clopidogrel, ticagrelor, etc.) PLUS aspirin. Revisit Dual Pathway Inhibition (DPI) in 3-6 months.

For claudication symptoms consider:

Cilostazol 75mg BID: Do NOT use in the presence of heart failure or cardiomyopathy.

Warning - Aspirin Allergy & Bleed Risk! Consult a pharmacist or interventionalist for assistance.

Symptomatic PAD Plus Other Indication for Long-term Anticoagulation: Continue current antithrombotic therapy as prescribed.

For claudication symptoms consider:

Cilostazol 75mg BID: Do NOT use in the presence of heart failure or cardiomyopathy.

Literature

2024 Lower Extremity Peripheral Artery Disease Guideline-at-a-Glance. J Am Coll Cardiol. 2024 Jun 18;83(24):2605-2609. — Bates KJ, Moore MM, Cibotti-Sun M.
2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2024 Jun 11;149(24):e1313-e1410. — Gornik HL, et al.
Rivaroxaban in Peripheral Artery Disease after Revascularization. N Engl J Med. 2020 May 21;382(21):1994-2004. — Bonaca MP, Bauersachs RM, Anand SS, Debus ES, Nehler MR, Patel MR, Fanelli F, Capell WH, Diao L, Jaeger N, Hess CN, Pap AF, Kittelson JM, Gudz I, Mátyás L, Krievins DK, Diaz R, Brodmann M, Muehlhofer E, Haskell LP, Berkowitz SD, Hiatt WR.
Antiplatelet Therapy For High Bleeding Risk Patients Undergoing PCI. 25 April 2020. — American College of Cardiology
Bleeding complications with dual antiplatelet therapy among patients with stable vascular disease or risk factors for vascular disease: results from the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial. Circulation. 2010 Jun 15;121(23):2575-83. — Berger PB, Bhatt DL, Fuster V, Steg PG, Fox KA, Shao M, Brennan DM, Hacke W, Montalescot G, Steinhubl SR, Topol EJ; CHARISMA Investigators.
2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017 Mar 21;135(12):e686-e725. — Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, Fleisher LA, Fowkes FG, Hamburg NM, Kinlay S, Lookstein R, Misra S, Mureebe L, Olin JW, Patel RA, Regensteiner JG, Schanzer A, Shishehbor MH, Stewart KJ, Treat-Jacobson D, Walsh ME.
Antithrombotic therapies in aortic and peripheral arterial diseases in 2021: a consensus document from the ESC working group on aorta and peripheral vascular diseases, the ESC working group on thrombosis, and the ESC working group on cardiovascular pharmacotherapy. Eur Heart J. 2021 Oct 14;42(39):4013-4024. — Aboyans V, Bauersachs R, Mazzolai L, Brodmann M, Palomares JFR, Debus S, Collet JP, Drexel H, Espinola-Klein C, Lewis BS, Roffi M, Sibbing D, Sillesen H, Stabile E, Schlager O, De Carlo M.

All questions & possible results

Literature

Related evaluations

Also from OSU Center for Health Sciences

Hestia Criteria for Pulmonary Embolism Evaluation (In- vs. Out-patient Tx)

OSU Antithrombotic Management of Asymptomatic PAD Without Revascularization

OSU Antithrombotic PAD Management Post Revascularization

OSU Peripheral Arterial Disease (PAD) Screening Tool

Peripheral Arterial Disease (PAD) Symptom Checker

Quality of Life Survey (VASCUQOL-6)

Simplified PESI (Pulmonary Embolism Severity Index: sPESI)

UConn Ankle Brachial Pressure Index Measurement (ABPI) Calculator