What is the most appropriate medication adjustment for a 67-year-old male with coronary artery disease (CAD), hypertension, and peripheral arterial disease (PAD) presenting with worsening intermittent claudication, currently taking aspirin (acetylsalicylic acid) 81 milligrams orally daily, atorvastatin 40 milligrams orally daily, and amlodipine (calcium channel blocker) 10 milligrams orally daily, with a history of three-vessel coronary artery bypass grafting (CABG) and an abnormal ankle-brachial index (ABI) indicating severe peripheral artery disease?

From the Guidelines

The most appropriate adjustment to JT's medication regimen would be to add rivaroxaban 2.5 mg orally twice daily to his existing aspirin therapy. This patient has peripheral arterial disease (PAD) with worsening claudication symptoms that are affecting his quality of life, as evidenced by his low ankle-brachial indices (ABI) of 0.60 and 0.70. According to the 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS guideline for the management of lower extremity peripheral artery disease 1, rivaroxaban (2.5 mg twice daily) combined with low-dose aspirin (81 mg daily) is effective in preventing major adverse cardiovascular events and major adverse limb events in patients with PAD who are not at increased risk of bleeding.

The VOYAGER PAD trial, as referenced in the guideline 1, assessed a regimen of low-dose rivaroxaban (2.5 mg twice daily) in addition to low-dose aspirin in patients within 10 days of lower extremity revascularization who were not on anticoagulation for another indication or had planned P2Y12 receptor antagonist use, and found that this regimen reduced the risk of a composite endpoint of MACE and MALE compared with aspirin alone.

Key points to consider in JT's management include:

• The importance of antiplatelet and antithrombotic therapy in patients with PAD, as outlined in the guideline 1
• The role of rivaroxaban in combination with aspirin for preventing major adverse cardiovascular and limb events in patients with PAD, as demonstrated in the VOYAGER PAD trial 1
• The need to balance the benefits of antithrombotic therapy with the risks of bleeding, particularly in patients with a history of coronary artery disease and PAD.

In this case, adding rivaroxaban 2.5 mg orally twice daily to JT's existing aspirin therapy is the most appropriate adjustment to his medication regimen, as it is supported by the most recent and highest quality evidence 1.

From the FDA Drug Label

XARELTO, in combination with aspirin, is indicated to reduce the risk of major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in adult patients with coronary artery disease. XARELTO, in combination with aspirin, is indicated to reduce the risk of major thrombotic vascular events (myocardial infarction, ischemic stroke, acute limb ischemia, and major amputation of a vascular etiology) in adult patients with PAD, including patients who have recently undergone a lower extremity revascularization procedure due to symptomatic PAD. Reduction of Risk of Major Thrombotic Vascular Events in PAD, Including Patients after Lower Extremity Revascularization due to Symptomatic PADNo dose adjustment needed based on CrCl2. 5 mg twice daily, plus aspirin (75–100 mg) once daily.

The most appropriate adjustment to JT's medications at this time would be to add rivaroxaban 2.5 mg orally twice daily to his current regimen of aspirin, as this combination is indicated to reduce the risk of major thrombotic vascular events in patients with PAD 2.

From the Research

Medication Adjustment for JT

To determine the most appropriate adjustment to JT's medications, we need to consider his medical history and current symptoms. JT has a history of coronary artery disease, hypertension, and peripheral arterial disease (PAD), and is currently experiencing worsening intermittent claudication.

Current Medications

JT is currently taking:

• Aspirin 81 mg orally daily
• Atorvastatin 40 mg orally daily
• Amlodipine 10 mg orally daily

Options for Medication Adjustment

The options for medication adjustment are:

• Add rivaroxaban 2.5 mg orally twice daily
• Add clopidogrel 75 mg orally daily
• Stop aspirin, and add rivaroxaban 5 mg orally twice daily
• Stop aspirin, and add vorapaxar 2.08 mg orally daily

Evidence-Based Recommendations

Based on the evidence from the studies, the most appropriate adjustment to JT's medications would be to add rivaroxaban 2.5 mg orally twice daily to his current regimen. This is supported by the following studies:

• The VOYAGER PAD trial 3 demonstrated that rivaroxaban plus aspirin reduced the risk of adverse cardiovascular and limb events in patients with PAD.
• The COMPASS trial 4, 5, 6 showed that the combination of low-dose rivaroxaban and aspirin reduced the risk of major adverse cardiovascular events in patients with chronic coronary artery disease or PAD.
• A meta-analysis of the COMPASS and VOYAGER trials 7 found that low-dose rivaroxaban plus aspirin was superior to aspirin alone in reducing cardiovascular and limb outcomes in patients with PAD.

Key Points

• The addition of rivaroxaban 2.5 mg orally twice daily to JT's current regimen is supported by the evidence from the VOYAGER PAD trial and the COMPASS trial.
• The combination of low-dose rivaroxaban and aspirin has been shown to reduce the risk of major adverse cardiovascular events in patients with PAD.
• The meta-analysis of the COMPASS and VOYAGER trials found that low-dose rivaroxaban plus aspirin was superior to aspirin alone in reducing cardiovascular and limb outcomes in patients with PAD.