Vorapaxar for Prevention of Major Adverse Cardiovascular and Limb Events in Peripheral Artery Disease.

Peripheral artery disease (PAD) is a severe manifestation of atherosclerosis. Patients with PAD are at heightened risk for atherothrombotic complications, including myocardial infarction and stroke (MACE); however, there is also an equal or greater risk of major adverse limb events (MALE), such as acute limb ischemia (ALI) and major amputation. Therefore, there is a need for effective medical therapies to reduce the risk of both MACE and MALE. Recent trials have demonstrated the role of thrombin inhibition in reducing the risk of MACE and MALE in PAD patients. One such medical therapy, vorapaxar, is a potent inhibitor of protease activated receptor-1 which mediates the cellular effects of thrombin. Vorapaxar, used in addition to aspirin, has demonstrated robust reductions in MACE and MALE in PAD patients. In this article, we provide a contemporary review of the current state of PAD and the role of antithrombotic medications in the treatment of PAD, as well as the current clinical data on vorapaxar and strategies to integrate vorapaxar into contemporary medical management of peripheral artery disease.

Evidence-Experience Gap and Future Perspective on the Treatment of Peripheral Artery Disease.

Peripheral artery disease (PAD) is a systemic disease associated with impaired limb function, poor quality of life, and increased cardiovascular morbidity. Its incidence has been dramatically increasing over years because of the emergence of an aging society and the increase in the number of patients with atherosclerotic risk factors. The clustering of these risk factors promotes disease development, reportedly leading to the differential location of atherosclerotic lesions in lower extremity arteries. The clinical presentations of PAD include intermittent claudication and chronic limb-threatening ischemia (CLTI). PAD is associated with a high risk of mortality and morbidity from both cardiovascular and limb events. The therapeutic goals for patients with PAD include 1) relief from PAD-related limb symptoms, 2) the prevention of new-onset and the development and recurrence of PAD, and 3) the prevention of concomitant adverse events due to coronary artery disease (CAD) and cerebrovascular disease (CVD). There are several types of antithrombotic agents, and their main role in patients with PAD is to reduce systemic events mainly including cardiovascular and lower extremity-related events. Currently, the efficacy of direct oral anticoagulant (DOAC) is also suggested by recent clinical trials. Although endovascular therapy (EVT) has been a first-line revascularization strategy for symptomatic PAD, whether clinical outcomes after EVT are comparable to those after surgical bypass therapy remains inconclusive.