A 61-year-old male complains about severe cramping calf pain after walking a few blocks, associated with mild rest pain. He also complains of a cold right lower limb and ipsilateral "odd prickling" sensation. His past medical history includes hypertension, diabetes, and dyslipidemia, which are treated appropriately. He smokes one pack/day for the last 15 years. His vital signs are normal, except for a slightly increased blood pressure. He has palpable pulses throughout. His left lower limb and foot are well perfused and warm, while the right foot is cold and pale. No pain is elicited during passive movement of his legs, relatively to his hips. His resting ankle-branchial index (ABI) is 0.8 and it does not change after exercise. Neurological examination is normal. The patient was admitted to the hospital for imaging and further evaluation. De novo infrainguinal atherosclerotic lesions in the right superficial femoral artery were identified and treated endovascularly with primary stenting.
Which of the following listed drugs/drug combinations would be the most appropriate, chronic therapeutic approach after endovascular intervention in order to reduce major cardiovascular and adverse limb ischemic events?
Show Answer
The correct answer is: F. Rivaroxaban plus ASA
Antiplatelet (anti-PLT) monotherapy has been shown to reduce major adverse cardiovascular event rates in patients with symptomatic peripheral arterial disease (PAD), although the absolute event rate reduction with monotherapy may be small.1 According to the Inter-Society Consensus Document on Management of Peripheral Arterial Disease (TASC) recommendations, single anti-PLT should be started before any endovascular procedure and should be continued lifelong.2 The American College of Cardiology and the American Heart Association (ACC/AHA) recommend at least 1 month of combined therapy with aspirin and clopidogrel after lower limb endovascular procedures (grade 2B).3 The clinical decision making for anti-PLT and/or antithrombotic therapy after endovascular or surgical bypass procedures is rapidly changing with the addition of direct acting oral anticoagulants (e.g. rivaroxaban). The recent COMPASS trial, comparing combined therapy with rivaroxaban and aspirin to monotherapy with either aspirin or rivaroxaban, demonstrated lower risk for major adverse cardiovascular events in the combined group.4,5 However, the safety and efficacy of this antithrombotic approach in patients with symptomatic PAD requiring revascularization remains unclear.
The VOYAGER PAD trial evaluated the outcomes of rivaroxaban (2.5mg/ twice daily) versus placebo added to anti-PLT (100mg/daily aspirin) in patients undergoing revascularization for peripheral arterial lesions.6,7 A total of 6,564 patients underwent randomization, with 3,286 being assigned to the rivaroxaban group, and 3,278 being assigned to the placebo group. The primary efficacy end point was a composite of myocardial infarction, ischemic stroke, cardiovascular death, acute limb ischemia, and major amputation of vascular etiology. The 3-year Kaplan Meier estimates of the primary outcome was 17.3% versus 19.9% for the rivaroxaban versus placebo group, reflecting a lower risk for adverse events among the rivaroxaban group (HR: 0.85; 95% CI: 0.76-0.96; p=0.009). Additionally, patients treated with rivaroxaban were at slightly higher risk for major bleeding as defined by the International Society on Thrombosis and Hemostasis (HR: 1.42; 95% CI: 1.10-1.84; p=0.007). Thus, the VOYAGER PAD supported the prescription of rivaroxaban at a dose of 2.5mg twice daily plus aspirin for prevention of major cardiovascular and major limb adverse ischemic events after lower extremity revascularization for symptomatic PAD. Considering the promising results of the combined aspirin and rivaroxaban therapy, wide application of continuous combined antiplatelet and antithrombotic therapy has the potential to improve the efficacy and long-term durability of revascularization interventions, while also minimizing cardiovascular risk.
Educational Objective
Rivaroxaban added to aspirin could be used after lower limb revascularization procedures for cardiovascular and major limb ischemic events prevention.
References
Armstrong EJ, Anderson DR, Yeo KK, et al. Association of dual-antiplatelet therapy with reduced major adverse cardiovascular events in patients with symptomatic peripheral arterial disease. J Vasc Surg 2015;62:157-65.
Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FGR. Inter-society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg 2007;45:S5-67.
Hess CN, Norgren L, Ansel GM, et al. A structured review of antithrombotic therapy in peripheral artery disease with a focus on revascularization: a TASC (InterSociety Consensus for the Management of Peripheral Artery Disease) initiative. Circulation 2017;135:2534-55.
Anand SS, Bosch J, Eikelboom JW, et al. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet 2018;391:219-29.
Connolly SJ, Eikelboom JW, Bosch J, et al. Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet 2018;391:205-18.
Capell WH, Bonaca MP, Nehler MR, et al. Rationale and design for the vascular outcomes study of ASA along with rivaroxaban in endovascular or surgical limb revascularization for peripheral artery disease (VOYAGER PAD). Am Heart J 2018;199:83-91.
Bonaca MP, Bauersachs RM, Anand SS, et al. Rivaroxaban in peripheral artery disease after revascularization. N Engl J Med 2020;382:1994-2004.
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