Peripheral Artery Disease: Revascularization vs Medical Therapy and VOYAGER PAD Data

Antithrombotic Therapy: COMPASS and VOYAGER PAD

The COMPASS trial demonstrated that rivaroxaban 2.5 mg BID plus aspirin reduced MACE (including stroke) and major adverse limb events (MALE) by 28% compared to aspirin alone in stable PAD (HR 0.72, 95% CI 0.57-0.90), with a 46% reduction in major amputation[3]. The VOYAGER PAD trial (related: ACS management) extended this to post-revascularization patients, showing rivaroxaban 2.5 mg BID plus aspirin reduced the composite of acute limb ischemia, major amputation, MI, ischemic stroke, or CV death by 15% (HR 0.85, 95% CI 0.76-0.96)[2] without significantly increased ISTH major bleeding (TIMI major bleeding 2% both arms). Dual-pathway inhibition is now recommended for symptomatic PAD patients at high limb event risk who are not at high bleeding risk.

Structured Exercise Programs

Supervised exercise therapy (SET) remains underutilized despite strong evidence: Medicare approved coverage for SET in PAD beginning in 2017. Programs typically involve 36 sessions over 12 weeks of treadmill walking to moderate-to-severe claudication, resting, and repeating for 30-50 minutes. The ERASE trial demonstrated SET improved 6-minute walk distance by 53 meters versus usual care (p<0.001). Home-based exercise programs with wearable activity monitors are emerging as alternatives, with the GOALS trial showing similar improvement in walking distance with structured home exercise versus supervised programs at 12 months.

A Practical Clinical Framework

For the patient presenting with claudication, the management pathway proceeds as follows. First, establish the diagnosis with ankle-brachial index and confirm severity. Second, initiate guideline-directed medical therapy and refer for supervised exercise. Third, reassess after three or more months: if symptoms remain lifestyle-limiting despite optimized medical management and exercise, revascularization is reasonable. For the patient presenting with chronic limb-threatening ischemia — rest pain, non-healing wounds, gangrene — vascular imaging and revascularization assessment should occur urgently, with the BEST-CLI data guiding the choice between bypass and endovascular approaches based on conduit availability. Throughout, the systemic nature of PAD demands that cardiovascular risk reduction — statin therapy, antithrombotic optimization, blood pressure and diabetes management — remains the backbone of care regardless of limb-specific interventions.

Limitations and Ongoing Debates

The BEST-CLI results strongly favor bypass with autogenous vein for CLTI, but many patients either lack adequate conduit or have comorbidities that make open surgery prohibitively risky — endovascular approaches remain necessary regardless of the trial data. Dual-pathway inhibition with low-dose rivaroxaban plus aspirin improves limb outcomes but increases bleeding, and the net clinical benefit depends on individual bleeding risk profiles. Supervised exercise therapy, despite strong evidence, is accessed by only a fraction of eligible patients due to program availability and coverage barriers. The most impactful intervention for many PAD patients is not a drug or procedure but systematic identification and medical optimization of a disease that remains underrecognized in primary care.

References

1. Surgical or Endovascular Revascularization for Chronic Limb-Threatening Ischemia
2. Rivaroxaban in Peripheral Artery Disease after Revascularization
3. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease
4. Supervised exercise, stent revascularization, or medical therapy for claudication due to aortoiliac peripheral artery disease: the CLEVER study
5. Drug-coated balloon versus standard percutaneous transluminal angioplasty for the treatment of superficial femoral and popliteal peripheral artery disease: IN.PACT SFA trial results